436:. Dendrimers with hydrophobic core and hydrophilic periphery have shown to exhibit micelle-like behavior and have container properties in solution. The use of dendrimers as unimolecular micelles was proposed by Newkome in 1985. This analogy highlighted the utility of dendrimers as solubilizing agents. The majority of drugs available in pharmaceutical industry are hydrophobic in nature and this property in particular creates major formulation problems. This drawback of drugs can be ameliorated by dendrimeric scaffolding, which can be used to encapsulate as well as to solubilize the drugs because of the capability of such scaffolds to participate in extensive hydrogen bonding with water. Dendrimer labs are trying to manipulate dendrimer's solubilizing trait, to explore dendrimers for drug delivery and to target specific carriers.
495:(PEG) is a common modification for dendrimers to modify their surface charge and circulation time. Surface charge can influence the interactions of dendrimers with biological systems, such as amine-terminal modified dendrimers which have a propensity to interact with cell membranes with anionic charge. Certain in vivo studies have shown polycationic dendrimers to be cytotoxic through membrane permeabilization, a phenomenon that could be partially mitigated via addition of PEGylation caps on amine groups, resulting in lower cytotoxicity and lower red blood cell hemolysis. Additionally, studies have found that PEGylation of dendrimers results in higher drug loading, slower drug release, longer circulation times in vivo, and lower toxicity in comparison to counterparts without PEG modifications.
773:(NSAID) increases when they are encapsulated in PAMAM dendrimers. This study shows the enhancement of NSAID solubility is due to the electrostatic interactions between the surface amine groups in PAMAM and the carboxyl groups found in NSAIDs. Contributing to the increase in solubility are the hydrophobic interactions between the aromatic groups in the drugs and the interior cavities of the dendrimer. When a drug is encapsulated within a dendrimer, its physical and physiological properties remains unaltered, including non-specificity and toxicity. However, when the dendrimer and the drug are covalently linked together, it can be used for specific tissue targeting and controlled release rates. Covalent conjugation of multiple drugs on dendrimer surfaces can pose a problem of insolubility.
489:. In the case of a dendrimer prodrug structure, linking of a drug to a dendrimer may be direct or linker-mediated depending on desired release kinetics. Such a linker may be pH-sensitive, enzyme catalyzed, or a disulfide bridge. The wide range of terminal functional groups available for dendrimers allows for many different types of linker chemistries, providing yet another tunable component on the system. Key parameters to consider for linker chemistry are (1) release mechanism upon arrival to the target site, whether that be within the cell or in a certain organ system, (2) drug-dendrimer spacing so as to prevent lipophilic drugs from folding into the dendrimer, and (3) linker degradability and post-release trace modifications on drugs.
291:, and then another ethylenediamine to make the generation-0 (G-0) PAMAM. Successive reactions create higher generations, which tend to have different properties. Lower generations can be thought of as flexible molecules with no appreciable inner regions, while medium-sized (G-3 or G-4) do have internal space that is essentially separated from the outer shell of the dendrimer. Very large (G-7 and greater) dendrimers can be thought of more like solid particles with very dense surfaces due to the structure of their outer shell. The functional group on the surface of PAMAM dendrimers is ideal for
639:. This intrinsic targeting has enabled drug delivery in a variety of conditions, ranging from cerebral palsy and other neuroinflammatory disorders to traumatic brain injury and hypothermic circulatory arrest, across a variety of animal models ranging from mice and rabbits to canines. Dendrimer uptake into the brain correlates with severity of inflammation and BBB impairment and it is believed that the BBB impairment is the key driving factor allowing dendrimer penetration. Localization is heavily skewed towards activated
87:
366:
345:
325:
205:
resulting dendrimer is considered a third generation dendrimer. Each successive generation results in a dendrimer roughly twice the molecular weight of the previous generation. Higher generation dendrimers also have more exposed functional groups on the surface, which can later be used to customize the dendrimer for a given application. Dendrimers may have a single surface functional group, or may be modified to allow for multiple functional groups on the surface.
514:(EGFRs) are often overexpressed in brain tumors, EGFRs are a convenient target for site-specific drug delivery. The delivery of boron to cancerous cells is important for effective neutron capture therapy, a cancer treatment which requires a large concentration of boron in cancerous cells and a low concentration in healthy cells. A boronated dendrimer conjugated with a monoclonal antibody drug that targets EGFRs was used in rats to successfully
456:
95:
214:
81:
constitutional repeating units the free valence is treated as a connection to a CRU. Note 2: A dendrimer molecule comprising only one dendron is sometimes referred to as dendron, monodendron or functionalised dendron. The use of the terms 'dendron' or 'monodendron' in the meaning of molecule or substance is not acceptable. Note 3: In a dendron, macrocycles of constitutional units are absent.
336:. Each step of the reaction must be driven to full completion to prevent mistakes in the dendrimer, which can cause trailing generations (some branches are shorter than the others). Such impurities can impact the functionality and symmetry of the dendrimer, but are extremely difficult to purify out because the relative size difference between perfect and imperfect dendrimers is very small.
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approved to treat bacterial vaginosis and prevent the spread of HIV, HPV, and HSV in Europe, Southeast Asia, Japan, Canada, and
Australia. Due to SPL7013’s broad antiviral action, it has recently been tested by the company as a potential drug to treat SARS-CoV-2. The company states preliminary in-vitro studies show high efficacy in preventing SARS-CoV-2 infection in cells.
20:
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acid and phenol-terminated water-soluble dendrimers were synthesized to establish their utility in drug delivery as well as conducting chemical reactions in their interiors. This might allow researchers to attach both targeting molecules and drug molecules to the same dendrimer, which could reduce negative side effects of medications on healthy cells.
788:. Results from these research has shown that dendrimers have increased aqueous solubility, slowed release rate, and possibly control cytotoxicity of the drugs. Cisplatin has been conjugated to PAMAM dendrimers that resulted in the same pharmacological results as listed above, but the conjugation also helped in accumulating
3850:"Elimination of Interface Energy Barriers Using Dendrimer Polyelectrolytes with Fractal Geometry" E. Ros, T. Tom, P. Ortega, I. Martin, E. Maggi, J. M. Asensi, J. López-Vidrier, E. Saucedo, J. Bertomeu, J. Puigdollers, and C. Voz ACS Applied Materials & Interfaces 2023 15 (23), 28705-28715 DOI: 10.1021/acsami.3c01930
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vehicles for drug delivery, which are different from the polymers currently used for this purpose. A study by
Vanndamme and Bobeck used PAMAM dendrimers as ophthalmic delivery vehicles in rabbits for two model drugs and measured the ocular residence time of this delivery to be comparable and in
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Intravenous dendrimer delivery shows promise as gene vectors to deliver genes to various organs in the body, and even tumors. One study found that through intravenous injection, a combination of PPI dendrimers and gene complexes resulted in gene expression in the liver, and another study showed that
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The cellular uptake mechanism of dendrimers can also be tuned using chemical targeting modifications. Non-modified PAMAM-G4 dendrimer is taken up into activated microglia by fluid phase endocytosis. Conversely, mannose modification of hydroxyl PAMAM-G4 dendrimers was able to change the mechanism of
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systems. In other words, one dendrimer molecule has hundreds of possible sites to couple to an active species. Researchers aimed to utilize the hydrophobic environments of the dendritic media to conduct photochemical reactions that generate the products that are synthetically challenged. Carboxylic
80:
Part of a molecule with only one free valence, comprising exclusively dendritic and terminal constitutional repeating units and in which each path from the free valence to any end-group comprises the same number of constitutional repeating units. Note 1: For the purpose of determining the nature of
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Dendrimers in drug-delivery systems is an example of various host–guest interactions. The interaction between host and guest, the dendrimer and the drug, respectively, can either be hydrophobic or covalent. Hydrophobic interaction between host and guest is considered "encapsulated," while covalent
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can be used to achieve site- or cell-specific delivery, and it has been shown that these peptides increase in targeting specificity when paired with dendrimers. Specifically, gemcitabine-loaded YIGSR-CMCht/PAMAM, a unique kind of dendrimer nanoparticle, induces a targeted mortality on these cancer
672:
to the required parts of a cell includes many challenges. Current research is being performed to find ways to use dendrimers to traffic genes into cells without damaging or deactivating the DNA. To maintain the activity of DNA during dehydration, the dendrimer/DNA complexes were encapsulated in a
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of many drugs tends to be very low. Dendrimers can be used to increase the solubility and stability of orally-administered drugs and increase drug penetration through the intestinal membrane. The bioavailability of PAMAM dendrimers conjugated to a chemotherapeutic has been studied in mice; it was
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Dendrimers are also classified by generation, which refers to the number of repeated branching cycles that are performed during its synthesis. For example, if a dendrimer is made by convergent synthesis (see below), and the branching reactions are performed onto the core molecule three times, the
659:
Starpharma, an
Australian pharmaceutical company, has multiple products that have either already been approved for use or are in the clinical trial phase. SPL7013, also known as astodrimer sodium, is a hyperbranched polymer used in Starpharma’s VivaGel line of pharmaceuticals that is currently
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Wu G, Barth RF, Yang W, Chatterjee M, Tjarks W, Ciesielski MJ, Fenstermaker RA (January 2004). "Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy".
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metallic nanoparticles. Poly(amidoamide), or PAMAM, dendrimers are utilized for their tertiary amine groups at the branching points within the dendrimer. Metal ions are introduced to an aqueous dendrimer solution and the metal ions form a complex with the lone pair of electrons present at the
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properties are very highly tunable by varying dendrimer size, structure, and surface characteristics. While G9 dendrimers biodistribute very heavily to the liver and spleen, G6 dendrimers tend to biodistribute more broadly. As molecular weight increases, urinary clearance and plasma clearance
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Dendrimers are built from small molecules that end up at the surface of the sphere, and reactions proceed inward building inward and are eventually attached to a core. This method makes it much easier to remove impurities and shorter branches along the way, so that the final dendrimer is more
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Dendrimers can be considered to have three major portions: a core, an inner shell, and an outer shell. Ideally, a dendrimer can be synthesized to have different functionality in each of these portions to control properties such as solubility, thermal stability, and attachment of compounds for
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interactions are considered to be conjugated. The use of dendrimers in medicine has shown to improve drug delivery by increasing the solubility and bioavailability of the drug. In conjunction, dendrimers can increase both cellular uptake and targeting ability, and decrease drug resistance.
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Drug attachment to the dendrimer may be accomplished by (1) a covalent attachment or conjugation to the external surface of the dendrimer forming a dendrimer prodrug, (2) ionic coordination to charged outer functional groups, or (3) micelle-like encapsulation of a drug via a dendrimer-drug
49:
is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point or core. The difference between dendrons and dendrimers is illustrated in the top figure, but the terms are typically encountered interchangeably.
677:. Based on this method, PAMAM dendrimer/DNA complexes were used to encapsulate functional biodegradable polymer films for substrate mediated gene delivery. Research has shown that the fast-degrading functional polymer has great potential for localized transfection.
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Numerous targeting moieties have been used to modify dendrimer biodistribution and allow for targeting to specific organs. For example, folate receptors are overexpressed in tumor cells and are therefore promising targets for localized drug delivery of
3831:
Tatiya, Pyus D., et al. "Novel polyurea microcapsules using dendritic functional monomer: synthesis, characterization, and its use in self-healing and anticorrosive polyurethane coatings." Industrial & Engineering
Chemistry Research 52.4 (2013):
591:
The primary obstacle to transdermal drug delivery is the epidermis. Hydrophobic drugs have a very difficult time penetrating the skin layer, as they partition heavily into skin oils. Recently, PAMAM dendrimers have been used as delivery vehicles for
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Morgan MT, Nakanishi Y, Kroll DJ, Griset AP, Carnahan MA, Wathier M, et al. (December 2006). "Dendrimer-encapsulated camptothecins: increased solubility, cellular uptake, and cellular retention affords enhanced anticancer activity in vitro".
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Given the widespread use of pesticides, herbicides and insecticides in modern farming, dendrimers are also being used by companies to help improve the delivery of agrochemicals to enable healthier plant growth and to help fight plant diseases.
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Kaanumalle LS, Ramesh R, Murthy
Maddipatla VS, Nithyanandhan J, Jayaraman N, Ramamurthy V (June 2005). "Dendrimers as photochemical reaction media. Photochemical behavior of unimolecular and bimolecular reactions in water-soluble dendrimers".
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polymers used in ocular delivery. This result indicates that administered drugs were more active and had increased bioavailability when delivered via dendrimers than their free-drug counterparts. Additionally, photo-curable, drug-eluting
830:
Astruc D, Boisselier E, Ornelas C (April 2010). "Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine".
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Fernandes EG, Vieira NC, de
Queiroz AA, Guimaraes FE, Zucolotto V (2010). "Immobilization of Poly(propylene imine) Dendrimer/Nickel Phthalocyanine as Nanostructured Multilayer Films To Be Used as Gate Membranes for SEGFET pH Sensors".
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compounds and for the delivery of anticancer drugs. The physical characteristics of dendrimers, including their monodispersity, water solubility, encapsulation ability, and large number of functionalizable peripheral groups make these
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commercializes biocompatible bis-MPA dendrimers and
Dendritech is the only kilogram-scale producers of PAMAM dendrimers. NanoSynthons, LLC from Mount Pleasant, Michigan, USA produces PAMAM dendrimers and other proprietary dendrimers.
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exhibited by free heme. Dendritic functional polymer polyamidoamine (PAMAM) is used to prepare core shell structure i.e. microcapsules and utilized in formulation of self-healing coatings of conventional and renewable origins.
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tertiary amines. After complexation, the ions are reduced to their zerovalent states to form a nanoparticle that is encapsulated within the dendrimer. These nanoparticles range in width from 1.5 to 10 nanometers and are called
622:
Dendrimer drug delivery has also shown major promise as a potential solution for many traditionally difficult drug delivery problems. In the case of drug delivery to the brain, dendrimers are able to take advantage of the
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hydrogels have been used as corneal sutures applied directly to the eye. These hydrogel sutures have shown efficacy as a medical device in rabbit models that surpasses traditional sutures and minimizes corneal scarring.
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Luong D, Kesharwani P, Deshmukh R, Mohd Amin MC, Gupta U, Greish K, Iyer AK (October 2016). "PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery".
3796:
Twyman LJ, Ellis A, Gittins PJ (January 2012). "Pyridine encapsulated hyperbranched polymers as mimetic models of haeme containing proteins, that also provide interesting and unusual porphyrin-ligand geometries".
1950:
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Toms S, Carnachan SM, Hermans IF, Johnson KD, Khan AA, O'Hagan SE, et al. (August 2016). "Poly Ethoxy Ethyl
Glycinamide (PEE-G) Dendrimers: Dendrimers Specifically Designed for Pharmaceutical Applications".
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Antoni P, Hed Y, Nordberg A, Nyström D, von Holst H, Hult A, Malkoch M (2009). "Bifunctional dendrimers: from robust synthesis and accelerated one-pot postfunctionalization strategy to potential applications".
480:
Dendrimers are particularly versatile drug delivery devices due to the wide range of chemical modifications that can be made to increase in vivo suitability and allow for site-specific targeted drug delivery.
1693:
Noda K, Minatogawa Y, Higuchi T (March 1991). "Effects of hippocampal neurotoxicant, trimethyltin, on corticosterone response to a swim stress and glucocorticoid binding capacity in the hippocampus in rats".
3538:
Fu HL, Cheng SX, Zhang XZ, Zhuo RX (December 2007). "Dendrimer/DNA complexes encapsulated in a water soluble polymer and supported on fast degrading star poly(DL-lactide) for localized gene delivery".
643:. Dendrimer-conjugated N-acetyl cysteine has shown efficacy in vivo as an anti-inflammatory at more than 1000-fold lower dose than free drug on a drug basis, reversing the phenotype of cerebral palsy,
311:, it is difficult to synthesize dendrimers using either method. This makes dendrimers hard to make and very expensive to purchase. At this time, there are only a few companies that sell dendrimers;
181:
of functional molecules allows for the isolation of the active site, a structure that mimics that of active sites in biomaterials. Also, it is possible to make dendrimers water-soluble, unlike most
3841:
Chaudhari, Ashok B., et al. "Polyurethane prepared from neem oil polyesteramides for self-healing anticorrosive coatings." Industrial & Engineering
Chemistry Research 52.30 (2013): 10189-10197.
2706:
Singh P, Gupta U, Asthana A, Jain NK (November 2008). "Folate and folate-PEG-PAMAM dendrimers: synthesis, characterization, and targeted anticancer drug delivery potential in tumor bearing mice".
225:
is also commonly known by the name arborol. The figure outlines the mechanism of the first two generations of arborol through a divergent route (discussed below). The synthesis is started by
3278:
Kannan G, Kambhampati SP, Kudchadkar SR (October 2017). "Effect of anesthetics on microglial activation and nanoparticle uptake: Implications for drug delivery in traumatic brain injury".
1815:
Tomalia DA, Naylor AM, Goddard WA (1990). "Starburst
Dendrimers: Molecular-Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter".
503:. Folic acid conjugation to PAMAM dendrimers has been shown to increase targeting and decrease off-target toxicity while maintaining on-target cytotoxicity of chemotherapeutics such as
443:
to reach market. One dendrimer scaffold designed to achieve this is the polyethoxyethylglycinamide (PEE-G) dendrimer. This dendrimer scaffold has been designed and shown to have high
2826:
Carvalho MR, Carvalho CR, Maia FR, Caballero D, Kundu SC, Reis RL, Oliveira JM (November 2019). "Peptide‐Modified Dendrimer Nanoparticles for Targeted Therapy of Colorectal Cancer".
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to increase hydrophilicity, allowing greater drug penetration. These modifications act as polymeric transdermal enhancers allowing drugs to more easily penetrate the skin barrier.
3679:
Grabchev I, Staneva D, Chovelon JM (2010). "Photophysical investigations on the sensor potential of novel, poly(propylenamine) dendrimers modified with 1,8-naphthalimide units".
2035:
Thomas TP, Majoros IJ, Kotlyar A, Kukowska-Latallo JF, Bielinska A, Myc A, Baker JR (June 2005). "Targeting and inhibition of cell growth by an engineered dendritic nanodevice".
3906:
Cheng, Y.; Xu, T. (2005). "Dendrimers as Potential Drug Carriers. Part I. Solubilization of Non-Steroidal Anti-Inflammatory Drugs in the Presence of Polyamidoamine Dendrimers".
299:
particular applications. Synthetic processes can also precisely control the size and number of branches on the dendrimer. There are two defined methods of dendrimer synthesis,
924:
Fradet, Alain; Chen, Jiazhong; Hellwich, Karl-Heinz; Horie, Kazuyuki; Kahovec, Jaroslav; Mormann, Werner; Stepto, Robert F. T.; Vohlídal, Jiří; Wilks, Edward S. (2019-03-26).
3103:
Cheng Y, Man N, Xu T, Fu R, Wang X, Wang X, Wen L (March 2007). "Transdermal delivery of nonsteroidal anti-inflammatory drugs mediated by polyamidoamine (PAMAM) dendrimers".
3636:
Campos BB, Algarra M, Esteves da Silva JC (January 2010). "Fluorescent properties of a hybrid cadmium sulfide-dendrimer nanocomposite and its quenching with nitromethane".
2251:
Chauhan AS, Sridevi S, Chalasani KB, Jain AK, Jain SK, Jain NK, Diwan PV (July 2003). "Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin".
566:(PK/PD) profiles of a drug. As carriers, the PK/PD is no longer determined by the drug itself but by the dendrimer’s localization, drug release, and dendrimer excretion.
432:
Dendrimers can also be used as a solubilizing agent. Since their introduction in the mid-1980s, this novel class of dendrimer architecture has been a prime candidate for
2216:
Prajapati RN, Tekade RK, Gupta U, Gajbhiye V, Jain NK (2009). "Dendimer-mediated solubilization, formulation development and in vitro-in vivo assessment of piroxicam".
3495:
Fu HL, Cheng SX, Zhang XZ, Zhuo RX (December 2008). "Dendrimer/DNA complexes encapsulated functional biodegradable polymer for substrate-mediated gene delivery".
2527:"Doxorubicin Conjugation and Drug Linker Chemistry Alter the Intravenous and Pulmonary Pharmacokinetics of a PEGylated Generation 4 Polylysine Dendrimer in Rats"
965:
Bauer, Roland. E.; Enkelmann, Volker; Wiesler, Uwe M.; Berresheim, Alexander J.; Müllen, Klaus (2002). "Single-Crystal Structures of Polyphenylene Dendrimers".
463:
Approaches for delivering unaltered natural products using polymeric carriers is of widespread interest. Dendrimers have been explored for the encapsulation of
1338:
Hecht S, Fréchet JM (January 2001). "Dendritic Encapsulation of Function: Applying Nature's Site Isolation Principle from Biomimetics to Materials Science".
2629:
Kaminskas LM, Boyd BJ, Porter CJ (August 2011). "Dendrimer pharmacokinetics: the effect of size, structure and surface characteristics on ADME properties".
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631:(BBB) impairment to cross the BBB effectively in vivo. For example, hydroxyl-terminated PAMAM dendrimers possess an intrinsic targeting ability to inflamed
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To increase patient compliance with prescribed treatment, delivery of drugs orally is often preferred to other routes of drug administration. However oral
404:
Applications of dendrimers typically involve conjugating other chemical species to the dendrimer surface that can function as detecting agents (such as a
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Tekade RK, Dutta T, Gajbhiye V, Jain NK (June 2009). "Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics".
3138:
Vandamme TF, Brobeck L (January 2005). "Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide".
1202:
Hawker CJ, Fréchet JM (1990). "Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules".
54:
1301:
Liang CO, Fréchet JM (2005). "Incorporation of Functional Guest Molecules into an Internally Functionalizable Dendrimer through Olefin Metathesis".
2181:
Khopade AJ, Caruso F, Tripathi P, Nagaich S, Jain NK (January 2002). "Effect of dendrimer on entrapment and release of bioactive from liposomes".
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amongst others. Research in this field is vast and ongoing due to the potential for multiple detection and binding sites in dendritic structures.
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found that around 9% of dendrimer administered orally was found intact in circulation and that minimal dendrimer degradation occurred in the gut.
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in another reaction with the tricarboxylate, forming generation two. Further repetition of the two steps leads to higher generations of arborol.
3741:
1648:
Killops KL, Campos LM, Hawker CJ (April 2008). "Robust, efficient, and orthogonal synthesis of dendrimers via thiol-ene "click" chemistry".
3470:
1412:
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Dutta T, Garg M, Jain NK (June 2008). "Poly(propyleneimine) dendrimer and dendrosome mediated genetic immunization against hepatitis B".
776:
This principle is also being studied for cancer treatment application. Several groups have encapsulated anti-cancer medications such as:
3706:
Scott RW, Wilson OM, Crooks RM (January 2005). "Synthesis, characterization, and applications of dendrimer-encapsulated nanoparticles".
2099:"Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient"
624:
889:
Nanjwade BK, Bechra HM, Derkar GK, Manvi FV, Nanjwade VK (October 2009). "Dendrimers: emerging polymers for drug-delivery systems".
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water-soluble polymer, and then deposited on or sandwiched in functional polymer films with a fast degradation rate to mediate gene
1886:
Liu M, Kono K, Fréchet JM (March 2000). "Water-soluble dendritic unimolecular micelles: their potential as drug delivery agents".
980:
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Different generations of polyamidoamine dendrimers have recently been implemented as selective contacts in photovoltaic devices.
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receptors. Peptide dendrimers may be employed in the future to precisely target cancer cells and deliver chemotherapeutic agents.
3983:
Cheng, Y.; Xu, Z; Ma, M.; Xu, T. (2007). "Dendrimers as drug carriers: Applications in different routes of drug administration".
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3908:
2881:"Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model"
2000:
Gupta U, Agashe HB, Asthana A, Jain NK (March 2006). "Dendrimers: novel polymeric nanoarchitectures for solubility enhancement".
926:"Nomenclature and terminology for dendrimers with regular dendrons and for hyperbranched polymers (IUPAC Recommendations 2017)"
444:
1351:
1533:
1382:
1174:
Newkome GR, Yao Z, Baker GR, Gupta VK (1985). "Micelles. Part 1. Cascade molecules: a new approach to micelles. A -arborol".
1586:
Morgenroth F, Reuther E, Müllen K (1997). "Polyphenylene Dendrimers: From Three-Dimensional to Two-Dimensional Structures".
1154:"Treelike molecules branch out – chemist Donald A. Tomalia synthesized first dendrimer molecule – Chemistry – Brief Article"
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internalization to mannose-receptor (CD206) mediated endocytosis. Additionally, mannose modification was able to change the
138:. Dendrimer popularity then greatly increased, resulting in more than 5,000 scientific papers and patents by the year 2005.
1921:
Newkome GR, Yao Z, Baker GR, Gupta VK (1985). "Micelles Part 1. Cascade molecules: a new approach to micelles, A-arborol".
1843:
Fréchet JM (March 1994). "Functional polymers and dendrimers: reactivity, molecular architecture, and interfacial energy".
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McElhanon JR, McGrath DV (June 2000). "Toward chiral polyhydroxylated dendrimers. Preparation and chiroptical properties".
726:
353:
monodisperse. However dendrimers made this way are not as large as those made by divergent methods because crowding due to
697:
sensors using poly(propylene imine), cadmium-sulfide/polypropylenimine tetrahexacontaamine dendrimer composites to detect
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770:
593:
45:. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The word
3372:"Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest"
3064:"Synthetic anticancer gene medicine exploits intrinsic antitumor activity of cationic vector to cure established tumors"
3985:
1472:
Schlick, Kristian H.; Morgan, Joel R.; Weiel, Julianna J.; Kelsey, Melissa S.; Cloninger, Mary J. (September 1, 2011).
1049:
Buhleier E, Wehner W, Vogtle F (1978). ""Cascade"- and "Nonskid-Chain-like" Syntheses of Molecular Cavity Topologies".
515:
390:
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The dendrimer is assembled from a multifunctional core, which is extended outward by a series of reactions, commonly a
3231:"Intrinsic targeting of inflammatory cells in the brain by polyamidoamine dendrimers upon subarachnoid administration"
4099:
2329:"Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor"
874:
421:
2928:
Csaba N, Garcia-Fuentes M, Alonso MJ (July 2006). "The performance of nanocarriers for transmucosal drug delivery".
2288:"Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer"
1004:"Anion-induced dimerization of 5-fold symmetric cyanostars in 3D crystalline solids and 2D self-assembled crystals"
511:
2146:
Bhadra D, Bhadra S, Jain S, Jain NK (May 2003). "A PEGylated dendritic nanoparticulate carrier of fluorouracil".
1447:
1105:
Tomalia, Donald A. and Dewald, James R. (1983) "Dense star polymers having core, core branches, terminal groups"
806:
510:
Antibody-mediated targeting of dendrimers to cell targets has also shown promise for targeted drug delivery. As
439:
For dendrimers to be able to be used in pharmaceutical applications, they must surmount the required regulatory
158:
and high-molecular weight species. The first category includes dendrimers and dendrons, and the latter includes
4022:
600:
1721:
Machaiah JP (May 1991). "Changes in macrophage membrane proteins in relation to protein deficiency in rats".
967:
99:
31:
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Malik, N.; Evagorou, E.; Duncan, R. (1999). "Dendrimer-platinate: a novel approach to cancer chemotherapy".
1748:
Franc G, Kakkar A (November 2008). "Dendrimer design using Cu(I)-catalyzed alkyne-azide "click-chemistry"".
1153:
1817:
3943:
Cheng, Y.; Xu, T; Fu, R (2005). "Polyamidoamine dendrimers used as solubility enhancers of ketoprofen".
1613:
Franc G, Kakkar AK (June 2009). "Diels-Alder "click" chemistry in designing dendritic macromolecules".
2286:
Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Majoros IJ, Thomas TP, et al. (June 2005).
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in the brain, verified using fluorescently labeled neutral generation dendrimers in a rabbit model of
312:
250:
226:
2526:
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3021:
1303:
433:
424:. Dendrimers have very strong potential for these applications because their structure can lead to
3869:
3421:"Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome"
2070:
Bhadra D, Bhadra S, Jain P, Jain NK (January 2002). "Pegnology: a review of PEG-ylated systems".
628:
486:
178:
3765:
Twyman LJ, Ge Y (April 2006). "Porphyrin cored hyperbranched polymers as heme protein models".
3370:
Mishra MK, Beaty CA, Lesniak WG, Kambhampati SP, Zhang F, Wilson MA, et al. (March 2014).
2432:
1657:
396:
There are ample avenues that can be opened by exploring this chemistry in dendrimer synthesis.
283:, or PAMAM, is perhaps the most well known dendrimer. The core of PAMAM is a diamine (commonly
3323:"Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model"
3229:
Dai H, Navath RS, Balakrishnan B, Guru BR, Mishra MK, Romero R, et al. (November 2010).
1400:
1120:
Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J, Smith P (1985).
198:
174:
146:
Dendritic molecules are characterized by structural perfection. Dendrimers and dendrons are
3419:
Nance E, Kambhampati SP, Smith ES, Zhang Z, Zhang F, Singh S, et al. (December 2017).
1852:
1312:
1091:
Denkewalter, Robert G. et al. (1981) "Macromolecular highly branched homogeneous compound"
648:
382:
370:
304:
159:
3321:
Kannan S, Dai H, Navath RS, Balakrishnan B, Jyoti A, Janisse J, et al. (April 2012).
8:
4104:
2525:
Leong NJ, Mehta D, McLeod VM, Kelly BD, Pathak R, Owen DJ, et al. (September 2018).
1951:"Synthesis, characterisation and guest-host properties of inverted unimolecular micelles"
1051:
801:
492:
300:
254:
72:
Molecule consisting of one or more dendrons emanating from a single constitutional unit.
2327:
Quintana A, Raczka E, Piehler L, Lee I, Myc A, Majoros I, et al. (September 2002).
1856:
1398:
Fischer M, Vögtle F (1999). "Dendrimers: From Design to Application—A Progress Report".
1316:
749:-mimetic centre significantly slows degradation compared to free heme, and prevents the
154:, spherical compounds. The field of dendritic molecules can be roughly divided into low-
90:
Crystal structure of a first-generation polyphenylene dendrimer reported by Müllen et al
3661:
3520:
3447:
3420:
3396:
3371:
3347:
3322:
3303:
3255:
3230:
3201:
3174:
3062:
Dufès C, Keith WN, Bilsland A, Proutski I, Uchegbu IF, Schätzlein AG (September 2005).
2997:
2972:
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2905:
2880:
2861:
2767:
2742:
2603:
2576:
2557:
2507:
2413:
2369:
2123:
2098:
1982:
1949:
Stevelmens S, Hest JC, Jansen JF, Boxtel DA, de Bravander-van den B, Miejer EW (1996).
1498:
1473:
1031:
386:
111:
3865:"Pharmaceutical applications of dendrimers: promising nanocarriers for drug discovery"
3471:"Starpharma (ASX:SPL) compound shows activity against coronavirus - The Market Herald"
2264:
2194:
2159:
1899:
459:
Scheme of a G-5 PAMAM dendrimer conjugated to both a dye molecule and a strand of DNA.
4076:
4072:
4059:
4039:
4002:
3962:
3925:
3888:
3814:
3778:
3723:
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2198:
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2128:
2079:
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2017:
1903:
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1703:
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1503:
1416:
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1283:
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1204:
1023:
984:
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870:
848:
742:
500:
246:
234:
170:
123:
3665:
3524:
2957:
2743:"Methotrexate delivery via folate targeted dendrimer-based nanotherapeutic platform"
2561:
2511:
1986:
1035:
1002:
Hirsch BE, Lee S, Qiao B, Chen CH, McDonald KP, Tait SL, Flood AH (September 2014).
307:. However, because the actual reactions consist of many steps needed to protect the
261:
step. Activation of the chain ends was achieved by converting the alcohol groups to
4068:
4031:
3994:
3954:
3917:
3878:
3806:
3770:
3715:
3688:
3645:
3618:
3582:
3547:
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3383:
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3307:
3287:
3250:
3242:
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3147:
3112:
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2715:
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2598:
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2541:
2491:
2456:
2417:
2397:
2373:
2351:
2343:
2299:
2260:
2225:
2190:
2155:
2118:
2110:
2044:
2009:
1972:
1964:
1931:
1895:
1860:
1825:
1789:
1753:
1667:
1622:
1595:
1493:
1485:
1408:
1347:
1320:
1275:
1240:
1212:
1184:
1133:
1060:
1015:
976:
937:
898:
840:
811:
563:
559:
440:
333:
280:
258:
177:, however, there are examples of dendrimers with internal functionality. Dendritic
155:
3586:
3551:
3291:
3151:
3080:
3063:
2896:
2460:
2304:
2287:
221:
One of the first dendrimers, the Newkome dendrimer, was synthesized in 1985. This
3958:
3921:
3692:
3338:
2681:
610:
580:
547:
417:
378:
292:
288:
284:
2879:
Sharma A, Porterfield JE, Smith E, Sharma R, Kannan S, Kannan RM (August 2018).
135:
4035:
3040:
2545:
1489:
902:
709:
636:
534:
354:
266:
115:
86:
3649:
3437:
2593:
2495:
2347:
1778:
1107:
1093:
1078:
4093:
3191:
2941:
2857:
1955:
1923:
1413:
10.1002/(SICI)1521-3773(19990401)38:7<884::AID-ANIE884>3.0.CO;2-K
1176:
951:
644:
469:
274:
222:
194:
163:
1864:
475:
4080:
4043:
4006:
3966:
3929:
3892:
3818:
3782:
3727:
3657:
3594:
3559:
3516:
3456:
3405:
3356:
3299:
3264:
3210:
3159:
3124:
3089:
3048:
3006:
2949:
2914:
2839:
2812:
2776:
2727:
2689:
2650:
2612:
2553:
2503:
2468:
2409:
2401:
2365:
2313:
2272:
2237:
2202:
2167:
2132:
2083:
2056:
2021:
1907:
1829:
1801:
1765:
1679:
1634:
1626:
1599:
1507:
1420:
1359:
1287:
1252:
1244:
1027:
988:
910:
852:
781:
777:
750:
721:
705:, and poly(propylenamine) first and second generation dendrimers for metal
698:
674:
530:
522:
504:
365:
344:
147:
131:
119:
1872:
1734:
1707:
1138:
1121:
942:
925:
324:
2356:
1064:
981:
10.1002/1521-3765(20020902)8:17<3858::AID-CHEM3858>3.0.CO;2-5
785:
605:
538:
cells. This is performed via selective interaction of the dendrimer with
464:
425:
413:
308:
186:
1935:
1216:
1188:
588:
a similar injection regressed the growth of tumors in observed animals.
3810:
1019:
632:
3998:
3719:
3622:
3387:
3246:
3116:
2988:
2971:
Thiagarajan G, Sadekar S, Greish K, Ray A, Ghandehari H (March 2013).
2848:
2804:
2719:
2642:
2624:
2622:
2229:
2048:
2013:
1977:
1968:
1793:
1671:
1324:
1279:
844:
3774:
3508:
2114:
1757:
1352:
10.1002/1521-3773(20010105)40:1<74::AID-ANIE74>3.0.CO;2-C
789:
702:
640:
185:, by functionalizing their outer shell with charged species or other
151:
34:
2758:
2574:
2034:
455:
2973:"Evidence of oral translocation of anionic G6.5 dendrimers in mice"
2747:
Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
2619:
2285:
1003:
270:
262:
190:
182:
3607:
4020:
D’Emanuele, A; Attwood, D (2005). "Dendrimer–drug interactions".
3883:
3864:
867:
Dendrimer Chemistry Concepts, Syntheses, Properties, Applications
539:
529:
has also been successful for targeted destruction of colorectal (
526:
447:
purity, stability, aqueous solubility and low inherent toxicity.
409:
238:
2666:
1549:
94:
4056:
964:
706:
690:
686:
3862:
2741:
Majoros IJ, Williams CR, Becker A, Baker JR (September 2009).
1573:
1082:
Denkewalter, Robert G., Kolc, Jaroslav, Lukasavage, William J.
213:
3635:
3369:
2825:
1122:"A New Class of Polymers: Starburst-Dendritic Macromolecules"
242:
2878:
2215:
2180:
1561:
189:
groups. Other controllable properties of dendrimers include
3320:
3277:
2970:
2575:
da Silva Santos S, Igne Ferreira E, Giarolla J (May 2016).
2386:
2250:
746:
567:
3982:
3418:
3061:
2740:
2445:
1948:
3228:
2927:
2097:
Asthana A, Chauhan AS, Diwan PV, Jain NK (October 2005).
888:
669:
476:
Role of dendrimer chemical modifications in drug delivery
405:
19:
2326:
1471:
1229:
553:
4019:
3678:
2481:
2096:
1585:
923:
829:
694:
558:
Dendrimers have the potential to completely change the
3019:
1999:
1119:
3863:
Cheng, Y.; Wang, J.; Rao, T.; He, X.; Xu, T. (2008).
2789:
2705:
2524:
1692:
64:
Substance composed of identical dendrimer molecules.
3175:"Nanotechnology approaches for ocular drug delivery"
3020:
Dufès C, Uchegbu IF, Schätzlein AG (December 2005).
2145:
2069:
1920:
1814:
1528:(2nd ed.). London: Academic Press of Elsevier.
1173:
1048:
865:
Vögtle, Fritz / Richardt, Gabriele / Werner, Nicole
3942:
3172:
2628:
1647:
472:appropriate candidates for drug delivery vehicles.
295:, which gives rise to many potential applications.
3795:
1588:Angewandte Chemie International Edition in English
741:Dendrimers are also being investigated for use as
169:The properties of dendrimers are dominated by the
3705:
1438:
1001:
663:
98:A first-generation "cyanostar" dendrimer and its
4091:
3537:
3494:
1696:The Japanese Journal of Psychiatry and Neurology
1265:
3905:
3137:
792:in solid tumors in intravenous administration.
348:Schematic of convergent synthesis of dendrimers
1885:
1372:
328:Schematic of divergent synthesis of dendrimers
3978:
3976:
3858:
3856:
3742:"Dendrimer technology licensed for herbicide"
3572:
1560:Dendritech Inc., from Midland, Michigan, USA.
1439:Holister P, Vas CR, Harper T (October 2003).
1397:
1201:
720:Dendrimers also are used in the synthesis of
571:decrease while terminal half-life increases.
110:by Fritz Vögtle in 1978, R.G. Denkewalter at
3179:Middle East African Journal of Ophthalmology
3102:
1337:
1300:
1747:
1612:
1474:"Clusters of ligands on dendrimer surfaces"
1434:
1432:
1430:
891:European Journal of Pharmaceutical Sciences
16:Highly ordered, branched polymeric molecule
3973:
3853:
1519:
1517:
1169:
1167:
685:Dendrimers have potential applications in
3882:
3446:
3436:
3395:
3346:
3254:
3200:
3190:
3079:
2996:
2904:
2847:
2766:
2602:
2592:
2355:
2303:
2122:
1976:
1661:
1523:
1497:
1137:
941:
533:) cancer cells in a co-culture scenario.
37:. Synonymous terms for dendrimer include
3764:
3173:Xu Q, Kambhampati SP, Kannan RM (2013).
1720:
1650:Journal of the American Chemical Society
1576:. NanoSynthons. Retrieved on 2015-09-29.
1427:
884:
882:
454:
364:
343:
323:
212:
93:
85:
18:
3946:European Journal of Medicinal Chemistry
3909:European Journal of Medicinal Chemistry
1842:
1514:
1377:. New York, NY: John Wiley & Sons.
1375:Dendrimers and Other Dendritic Polymers
1164:
127:
4092:
2183:International Journal of Pharmaceutics
2148:International Journal of Pharmaceutics
1723:Indian Journal of Experimental Biology
1548:Polymer Factory AB, Stockholm, Sweden.
617:
217:Synthesis to second generation arborol
107:
3224:
3222:
3220:
2701:
2699:
2662:
2660:
1441:"Dendrimers: Technology White Papers"
879:
732:
574:
554:Pharmacokinetics and pharmacodynamics
339:
2430:
1373:Frechet J, Tomalia DA (March 2002).
771:nonsteroidal anti-inflammatory drugs
727:dendrimer-encapsulated nanoparticles
550:in the rest of the body in rabbits.
319:
3708:The Journal of Physical Chemistry B
231:triethyl sodiomethanetricarboxylate
13:
3986:Journal of Pharmaceutical Sciences
3217:
3105:Journal of Pharmaceutical Sciences
2696:
2657:
2534:Journal of Pharmaceutical Sciences
760:
745:. Their steric bulk surrounding a
654:
377:Dendrimers have been prepared via
360:
162:, hyperbranched polymers, and the
106:The first dendrimers were made by
14:
4116:
668:The ability to deliver pieces of
651:and other inflammatory diseases.
512:epidermal growth factor receptors
422:pharmaceutically active compounds
273:. The tosyl group then served as
197:, tecto-dendrimer formation, and
4073:10.1097/00001813-199909000-00010
1782:The Journal of Organic Chemistry
1268:The Journal of Organic Chemistry
715:
604:some cases greater than current
516:deliver boron to cancerous cells
450:
4050:
4013:
3936:
3899:
3844:
3835:
3825:
3789:
3758:
3734:
3699:
3672:
3629:
3611:Journal of Physical Chemistry C
3601:
3566:
3531:
3488:
3463:
3412:
3363:
3314:
3271:
3166:
3131:
3096:
3055:
3013:
2964:
2930:Expert Opinion on Drug Delivery
2921:
2872:
2819:
2783:
2734:
2568:
2518:
2475:
2439:
2424:
2380:
2320:
2279:
2244:
2209:
2174:
2139:
2090:
2063:
2028:
1993:
1942:
1914:
1879:
1836:
1808:
1772:
1741:
1714:
1686:
1641:
1606:
1579:
1567:
1554:
1542:
1465:
1391:
1366:
1331:
1294:
1259:
1223:
1195:
1146:
1113:
1099:
807:Ferrocene-containing dendrimers
599:Dendrimers may also act as new
399:
4023:Advanced Drug Delivery Reviews
3327:Science Translational Medicine
3029:Advanced Drug Delivery Reviews
2037:Journal of Medicinal Chemistry
1085:
1071:
1042:
995:
958:
917:
859:
823:
664:Gene delivery and transfection
108:divergent synthesis approaches
1:
3587:10.1016/j.vaccine.2008.04.058
3552:10.1016/j.jconrel.2007.08.031
3540:Journal of Controlled Release
3292:10.1016/j.jconrel.2017.03.032
3280:Journal of Controlled Release
3152:10.1016/j.jconrel.2004.09.015
3140:Journal of Controlled Release
3081:10.1158/0008-5472.CAN-04-4402
3022:"Dendrimers in gene delivery"
2897:10.1016/j.jconrel.2018.06.003
2885:Journal of Controlled Release
2484:Journal of Microencapsulation
2461:10.1158/0008-5472.CAN-06-2066
2305:10.1158/0008-5472.can-04-3921
2265:10.1016/s0168-3659(03)00200-1
2253:Journal of Controlled Release
2195:10.1016/S0378-5173(01)00901-2
2160:10.1016/s0378-5173(03)00132-7
1900:10.1016/s0168-3659(99)00245-x
1888:Journal of Controlled Release
968:Chemistry: A European Journal
817:
507:, in mouse models of cancer.
141:
128:convergent synthetic approach
3959:10.1016/j.ejmech.2005.08.002
3922:10.1016/j.ejmech.2005.06.010
3693:10.1016/j.dyepig.2009.10.023
3497:The Journal of Gene Medicine
3425:Journal of Neuroinflammation
3339:10.1126/scitranslmed.3003162
2682:10.1016/j.actbio.2016.07.015
1446:. Cientifica. Archived from
357:along the core is limiting.
208:
122:in 1983 and in 1985, and by
7:
1818:Angew. Chem. Int. Ed. Engl.
795:
769:The solubility of various
10:
4121:
4036:10.1016/j.addr.2005.09.012
3041:10.1016/j.addr.2005.09.017
2546:10.1016/j.xphs.2018.05.013
1524:Hermanson GT (2008). "7".
1490:10.1016/j.bmcl.2011.03.100
930:Pure and Applied Chemistry
903:10.1016/j.ejps.2009.07.008
689:. Studied systems include
680:
3650:10.1007/s10895-009-0532-5
3438:10.1186/s12974-017-1004-5
2594:10.3390/molecules21060686
2496:10.1080/02652040802312572
313:Polymer Factory Sweden AB
287:), which is reacted with
251:lithium aluminium hydride
227:nucleophilic substitution
4100:Supramolecular chemistry
3192:10.4103/0974-9233.106384
2942:10.1517/17425247.3.4.463
412:, targeting components,
3870:Frontiers in Bioscience
3799:Chemical Communications
3767:Chemical Communications
3638:Journal of Fluorescence
2977:Molecular Pharmaceutics
2348:10.1023/a:1020398624602
2336:Pharmaceutical Research
2218:Molecular Pharmaceutics
1865:10.1126/science.8134834
1750:Chemical Communications
1526:Bioconjugate Techniques
1008:Chemical Communications
487:supramolecular assembly
3475:themarketherald.com.au
2840:10.1002/adtp.201900132
2793:Bioconjugate Chemistry
2708:Bioconjugate Chemistry
2402:10.1002/cmdc.201600270
1830:10.1002/anie.199001381
1627:10.1002/chem.200900252
1600:10.1002/anie.199706311
1245:10.1002/anie.200804987
460:
391:azide-alkyne reactions
374:
349:
329:
218:
103:
91:
83:
24:
2828:Advanced Therapeutics
1401:Angew. Chem. Int. Ed.
1139:10.1295/polymj.17.117
1108:U.S. patent 4,507,466
1094:U.S. patent 4,410,688
1079:U.S. patent 4,289,872
943:10.1515/pac-2016-1217
458:
383:Diels-Alder reactions
368:
347:
327:
229:of 1-bromopentane by
216:
97:
89:
59:
23:Dendrimer and dendron
22:
3746:www.labonline.com.au
2577:"Dendrimer Prodrugs"
1478:Bioorg Med Chem Lett
1065:10.1055/s-1978-24702
649:macular degeneration
434:host–guest chemistry
408:molecule), affinity
371:Diels-Alder reaction
305:convergent synthesis
160:dendronized polymers
30:are highly ordered,
1936:10.1021/jo00211a052
1857:1994Sci...263.1710F
1317:2005MaMol..38.6276L
1217:10.1021/ja00177a027
1189:10.1021/jo00211a052
802:Dendronized polymer
629:blood-brain barrier
618:Brain drug delivery
493:Polyethylene glycol
387:thiol-yne reactions
301:divergent synthesis
150:and usually highly
126:in 1985. In 1990 a
35:polymeric molecules
3811:10.1039/c1cc14396d
3581:(27–28): 3389–94.
2670:Acta Biomaterialia
2433:"PEE-G Dendrimers"
1020:10.1039/C4CC03725A
733:Other applications
575:Routes of delivery
535:Targeting peptides
461:
375:
350:
340:Convergent methods
330:
219:
130:was introduced by
112:Allied Corporation
104:
92:
68:Dendrimer molecule
25:
4060:Anti-Cancer Drugs
4030:(15): 2147–2162.
3999:10.1002/jps.21079
3953:(12): 1390–1393.
3916:(11): 1188–1192.
3877:(13): 1447–1471.
3720:10.1021/jp0469665
3681:Dyes and Pigments
3623:10.1021/jp9106052
3617:(14): 6478–6483.
3388:10.1021/nn404872e
3247:10.2217/nnm.10.89
3117:10.1002/jps.20745
2989:10.1021/mp300436c
2805:10.1021/bc0341674
2720:10.1021/bc800125u
2643:10.2217/nnm.11.67
2230:10.1021/mp8002489
2103:AAPS PharmSciTech
2049:10.1021/jm040187v
2014:10.1021/bm050802s
2002:Biomacromolecules
1969:10.1021/ja954207h
1963:(31): 7398–7399.
1794:10.1021/jo0503254
1672:10.1021/ja8006325
1535:978-0-12-370501-3
1484:(17): 5078–5083.
1384:978-0-471-63850-6
1340:Angewandte Chemie
1325:10.1021/ma050818a
1311:(15): 6276–6284.
1280:10.1021/jo000207a
1233:Angewandte Chemie
1211:(21): 7638–7647.
1205:J. Am. Chem. Soc.
1183:(11): 2003–2004.
975:(17): 3858–3864.
845:10.1021/cr900327d
743:blood substitutes
501:chemotherapeutics
320:Divergent methods
245:groups were then
235:dimethylformamide
175:molecular surface
171:functional groups
124:George R. Newkome
43:cascade molecules
4112:
4085:
4084:
4054:
4048:
4047:
4017:
4011:
4010:
3980:
3971:
3970:
3940:
3934:
3933:
3903:
3897:
3896:
3886:
3860:
3851:
3848:
3842:
3839:
3833:
3829:
3823:
3822:
3793:
3787:
3786:
3775:10.1039/b600831n
3762:
3756:
3755:
3753:
3752:
3738:
3732:
3731:
3703:
3697:
3696:
3676:
3670:
3669:
3633:
3627:
3626:
3605:
3599:
3598:
3570:
3564:
3563:
3535:
3529:
3528:
3509:10.1002/jgm.1258
3492:
3486:
3485:
3483:
3482:
3467:
3461:
3460:
3450:
3440:
3416:
3410:
3409:
3399:
3367:
3361:
3360:
3350:
3333:(130): 130ra46.
3318:
3312:
3311:
3275:
3269:
3268:
3258:
3226:
3215:
3214:
3204:
3194:
3170:
3164:
3163:
3135:
3129:
3128:
3100:
3094:
3093:
3083:
3059:
3053:
3052:
3035:(15): 2177–202.
3026:
3017:
3011:
3010:
3000:
2968:
2962:
2961:
2925:
2919:
2918:
2908:
2876:
2870:
2869:
2851:
2823:
2817:
2816:
2787:
2781:
2780:
2770:
2738:
2732:
2731:
2703:
2694:
2693:
2664:
2655:
2654:
2626:
2617:
2616:
2606:
2596:
2572:
2566:
2565:
2540:(9): 2509–2513.
2531:
2522:
2516:
2515:
2479:
2473:
2472:
2455:(24): 11913–21.
2443:
2437:
2436:
2428:
2422:
2421:
2384:
2378:
2377:
2359:
2333:
2324:
2318:
2317:
2307:
2283:
2277:
2276:
2248:
2242:
2241:
2213:
2207:
2206:
2178:
2172:
2171:
2143:
2137:
2136:
2126:
2115:10.1208/pt060367
2094:
2088:
2087:
2067:
2061:
2060:
2032:
2026:
2025:
1997:
1991:
1990:
1980:
1946:
1940:
1939:
1918:
1912:
1911:
1883:
1877:
1876:
1851:(5154): 1710–5.
1840:
1834:
1833:
1812:
1806:
1805:
1776:
1770:
1769:
1758:10.1039/b809870k
1745:
1739:
1738:
1718:
1712:
1711:
1690:
1684:
1683:
1665:
1645:
1639:
1638:
1610:
1604:
1603:
1583:
1577:
1571:
1565:
1558:
1552:
1546:
1540:
1539:
1521:
1512:
1511:
1501:
1469:
1463:
1462:
1460:
1458:
1452:
1445:
1436:
1425:
1424:
1395:
1389:
1388:
1370:
1364:
1363:
1335:
1329:
1328:
1298:
1292:
1291:
1263:
1257:
1256:
1227:
1221:
1220:
1199:
1193:
1192:
1171:
1162:
1161:
1150:
1144:
1143:
1141:
1117:
1111:
1110:
1103:
1097:
1096:
1089:
1083:
1081:
1075:
1069:
1068:
1046:
1040:
1039:
999:
993:
992:
962:
956:
955:
945:
921:
915:
914:
886:
877:
863:
857:
856:
833:Chemical Reviews
827:
812:Metallodendrimer
525:dendrimers with
385:, thiol-ene and
334:Michael reaction
281:Poly(amidoamine)
156:molecular weight
4120:
4119:
4115:
4114:
4113:
4111:
4110:
4109:
4090:
4089:
4088:
4055:
4051:
4018:
4014:
3981:
3974:
3941:
3937:
3904:
3900:
3861:
3854:
3849:
3845:
3840:
3836:
3830:
3826:
3794:
3790:
3769:(15): 1658–60.
3763:
3759:
3750:
3748:
3740:
3739:
3735:
3704:
3700:
3677:
3673:
3634:
3630:
3606:
3602:
3571:
3567:
3536:
3532:
3503:(12): 1334–42.
3493:
3489:
3480:
3478:
3469:
3468:
3464:
3417:
3413:
3368:
3364:
3319:
3315:
3276:
3272:
3227:
3218:
3171:
3167:
3136:
3132:
3101:
3097:
3074:(18): 8079–84.
3068:Cancer Research
3060:
3056:
3024:
3018:
3014:
2969:
2965:
2926:
2922:
2877:
2873:
2834:(11): 1900132.
2824:
2820:
2788:
2784:
2759:10.1002/wnan.37
2739:
2735:
2714:(11): 2239–52.
2704:
2697:
2665:
2658:
2627:
2620:
2573:
2569:
2529:
2523:
2519:
2480:
2476:
2449:Cancer Research
2444:
2440:
2429:
2425:
2385:
2381:
2331:
2325:
2321:
2298:(12): 5317–24.
2292:Cancer Research
2284:
2280:
2249:
2245:
2214:
2210:
2189:(1–2): 157–62.
2179:
2175:
2154:(1–2): 111–24.
2144:
2140:
2095:
2091:
2068:
2064:
2043:(11): 3729–35.
2033:
2029:
1998:
1994:
1947:
1943:
1930:(11): 155–158.
1919:
1915:
1894:(1–2): 121–31.
1884:
1880:
1841:
1837:
1813:
1809:
1777:
1773:
1752:(42): 5267–76.
1746:
1742:
1719:
1715:
1691:
1687:
1663:10.1.1.658.8715
1646:
1642:
1611:
1607:
1584:
1580:
1572:
1568:
1559:
1555:
1550:Polymer Factory
1547:
1543:
1536:
1522:
1515:
1470:
1466:
1456:
1454:
1450:
1443:
1437:
1428:
1396:
1392:
1385:
1371:
1367:
1336:
1332:
1299:
1295:
1264:
1260:
1239:(12): 2126–30.
1228:
1224:
1200:
1196:
1172:
1165:
1152:
1151:
1147:
1126:Polymer Journal
1118:
1114:
1106:
1104:
1100:
1092:
1090:
1086:
1077:
1076:
1072:
1047:
1043:
1014:(69): 9827–30.
1000:
996:
963:
959:
922:
918:
887:
880:
864:
860:
839:(4): 1857–959.
828:
824:
820:
798:
763:
735:
718:
683:
666:
657:
655:Clinical trials
620:
611:hyaluronic acid
581:bioavailability
577:
564:pharmacodynamic
560:pharmacokinetic
556:
548:biodistribution
478:
453:
402:
379:click chemistry
363:
361:Click chemistry
342:
322:
293:click chemistry
289:methyl acrylate
285:ethylenediamine
211:
144:
84:
58:
17:
12:
11:
5:
4118:
4108:
4107:
4102:
4087:
4086:
4067:(8): 767–776.
4049:
4012:
3993:(1): 123–143.
3972:
3935:
3898:
3852:
3843:
3834:
3824:
3788:
3757:
3733:
3714:(2): 692–704.
3698:
3687:(3): 189–193.
3671:
3628:
3600:
3565:
3530:
3487:
3462:
3411:
3382:(3): 2134–47.
3362:
3313:
3270:
3241:(9): 1317–29.
3216:
3165:
3130:
3111:(3): 595–602.
3095:
3054:
3012:
2963:
2920:
2871:
2818:
2782:
2733:
2695:
2656:
2637:(6): 1063–84.
2618:
2567:
2517:
2474:
2438:
2423:
2396:(15): 1583–6.
2379:
2319:
2278:
2243:
2208:
2173:
2138:
2109:(3): E536-42.
2089:
2062:
2027:
1992:
1941:
1913:
1878:
1835:
1824:(2): 138–175.
1807:
1788:(13): 5062–9.
1771:
1740:
1713:
1685:
1656:(15): 5062–4.
1640:
1621:(23): 5630–9.
1605:
1594:(6): 631–634.
1578:
1566:
1553:
1541:
1534:
1513:
1464:
1453:on 6 July 2011
1426:
1407:(7): 884–905.
1390:
1383:
1365:
1330:
1304:Macromolecules
1293:
1274:(11): 3525–9.
1258:
1222:
1194:
1163:
1145:
1112:
1098:
1084:
1070:
1059:(2): 155–158.
1041:
994:
957:
936:(3): 523–561.
916:
878:
858:
821:
819:
816:
815:
814:
809:
804:
797:
794:
762:
759:
734:
731:
717:
714:
710:photodetection
682:
679:
665:
662:
656:
653:
637:cerebral palsy
619:
616:
576:
573:
555:
552:
477:
474:
470:macromolecules
452:
449:
418:imaging agents
401:
398:
362:
359:
355:steric effects
341:
338:
321:
318:
275:leaving groups
267:tosyl chloride
210:
207:
143:
140:
116:Donald Tomalia
53:
52:
15:
9:
6:
4:
3:
2:
4117:
4106:
4103:
4101:
4098:
4097:
4095:
4082:
4078:
4074:
4070:
4066:
4062:
4061:
4053:
4045:
4041:
4037:
4033:
4029:
4025:
4024:
4016:
4008:
4004:
4000:
3996:
3992:
3988:
3987:
3979:
3977:
3968:
3964:
3960:
3956:
3952:
3948:
3947:
3939:
3931:
3927:
3923:
3919:
3915:
3911:
3910:
3902:
3894:
3890:
3885:
3880:
3876:
3872:
3871:
3866:
3859:
3857:
3847:
3838:
3828:
3820:
3816:
3812:
3808:
3804:
3800:
3792:
3784:
3780:
3776:
3772:
3768:
3761:
3747:
3743:
3737:
3729:
3725:
3721:
3717:
3713:
3709:
3702:
3694:
3690:
3686:
3682:
3675:
3667:
3663:
3659:
3655:
3651:
3647:
3644:(1): 143–51.
3643:
3639:
3632:
3624:
3620:
3616:
3612:
3604:
3596:
3592:
3588:
3584:
3580:
3576:
3569:
3561:
3557:
3553:
3549:
3545:
3541:
3534:
3526:
3522:
3518:
3514:
3510:
3506:
3502:
3498:
3491:
3476:
3472:
3466:
3458:
3454:
3449:
3444:
3439:
3434:
3430:
3426:
3422:
3415:
3407:
3403:
3398:
3393:
3389:
3385:
3381:
3377:
3373:
3366:
3358:
3354:
3349:
3344:
3340:
3336:
3332:
3328:
3324:
3317:
3309:
3305:
3301:
3297:
3293:
3289:
3285:
3281:
3274:
3266:
3262:
3257:
3252:
3248:
3244:
3240:
3236:
3232:
3225:
3223:
3221:
3212:
3208:
3203:
3198:
3193:
3188:
3184:
3180:
3176:
3169:
3161:
3157:
3153:
3149:
3145:
3141:
3134:
3126:
3122:
3118:
3114:
3110:
3106:
3099:
3091:
3087:
3082:
3077:
3073:
3069:
3065:
3058:
3050:
3046:
3042:
3038:
3034:
3030:
3023:
3016:
3008:
3004:
2999:
2994:
2990:
2986:
2983:(3): 988–98.
2982:
2978:
2974:
2967:
2959:
2955:
2951:
2947:
2943:
2939:
2936:(4): 463–78.
2935:
2931:
2924:
2916:
2912:
2907:
2902:
2898:
2894:
2890:
2886:
2882:
2875:
2867:
2863:
2859:
2855:
2850:
2845:
2841:
2837:
2833:
2829:
2822:
2814:
2810:
2806:
2802:
2799:(1): 185–94.
2798:
2794:
2786:
2778:
2774:
2769:
2764:
2760:
2756:
2753:(5): 502–10.
2752:
2748:
2744:
2737:
2729:
2725:
2721:
2717:
2713:
2709:
2702:
2700:
2691:
2687:
2683:
2679:
2675:
2671:
2663:
2661:
2652:
2648:
2644:
2640:
2636:
2632:
2625:
2623:
2614:
2610:
2605:
2600:
2595:
2590:
2586:
2582:
2578:
2571:
2563:
2559:
2555:
2551:
2547:
2543:
2539:
2535:
2528:
2521:
2513:
2509:
2505:
2501:
2497:
2493:
2490:(4): 287–96.
2489:
2485:
2478:
2470:
2466:
2462:
2458:
2454:
2450:
2442:
2434:
2427:
2419:
2415:
2411:
2407:
2403:
2399:
2395:
2391:
2383:
2375:
2371:
2367:
2363:
2358:
2357:2027.42/41493
2353:
2349:
2345:
2342:(9): 1310–6.
2341:
2337:
2330:
2323:
2315:
2311:
2306:
2301:
2297:
2293:
2289:
2282:
2274:
2270:
2266:
2262:
2259:(3): 335–43.
2258:
2254:
2247:
2239:
2235:
2231:
2227:
2224:(3): 940–50.
2223:
2219:
2212:
2204:
2200:
2196:
2192:
2188:
2184:
2177:
2169:
2165:
2161:
2157:
2153:
2149:
2142:
2134:
2130:
2125:
2120:
2116:
2112:
2108:
2104:
2100:
2093:
2085:
2081:
2077:
2073:
2072:Die Pharmazie
2066:
2058:
2054:
2050:
2046:
2042:
2038:
2031:
2023:
2019:
2015:
2011:
2008:(3): 649–58.
2007:
2003:
1996:
1988:
1984:
1979:
1974:
1970:
1966:
1962:
1958:
1957:
1956:J Am Chem Soc
1952:
1945:
1937:
1933:
1929:
1926:
1925:
1924:J. Org. Chem.
1917:
1909:
1905:
1901:
1897:
1893:
1889:
1882:
1874:
1870:
1866:
1862:
1858:
1854:
1850:
1846:
1839:
1831:
1827:
1823:
1820:
1819:
1811:
1803:
1799:
1795:
1791:
1787:
1783:
1775:
1767:
1763:
1759:
1755:
1751:
1744:
1736:
1732:
1728:
1724:
1717:
1709:
1705:
1701:
1697:
1689:
1681:
1677:
1673:
1669:
1664:
1659:
1655:
1651:
1644:
1636:
1632:
1628:
1624:
1620:
1616:
1609:
1601:
1597:
1593:
1589:
1582:
1575:
1570:
1563:
1557:
1551:
1545:
1537:
1531:
1527:
1520:
1518:
1509:
1505:
1500:
1495:
1491:
1487:
1483:
1479:
1475:
1468:
1449:
1442:
1435:
1433:
1431:
1422:
1418:
1414:
1410:
1406:
1403:
1402:
1394:
1386:
1380:
1376:
1369:
1361:
1357:
1353:
1349:
1345:
1341:
1334:
1326:
1322:
1318:
1314:
1310:
1306:
1305:
1297:
1289:
1285:
1281:
1277:
1273:
1269:
1262:
1254:
1250:
1246:
1242:
1238:
1234:
1226:
1218:
1214:
1210:
1207:
1206:
1198:
1190:
1186:
1182:
1179:
1178:
1177:J. Org. Chem.
1170:
1168:
1159:
1155:
1149:
1140:
1135:
1131:
1127:
1123:
1116:
1109:
1102:
1095:
1088:
1080:
1074:
1066:
1062:
1058:
1054:
1053:
1045:
1037:
1033:
1029:
1025:
1021:
1017:
1013:
1009:
1005:
998:
990:
986:
982:
978:
974:
970:
969:
961:
953:
949:
944:
939:
935:
931:
927:
920:
912:
908:
904:
900:
897:(3): 185–96.
896:
892:
885:
883:
876:
875:3-527-32066-0
872:
868:
862:
854:
850:
846:
842:
838:
834:
826:
822:
813:
810:
808:
805:
803:
800:
799:
793:
791:
787:
783:
779:
774:
772:
767:
761:Drug delivery
758:
755:
752:
748:
744:
739:
730:
728:
723:
716:Nanoparticles
713:
711:
708:
704:
700:
696:
692:
688:
678:
676:
671:
661:
652:
650:
646:
645:Rett syndrome
642:
638:
634:
630:
626:
615:
612:
607:
602:
597:
595:
589:
585:
582:
572:
569:
565:
561:
551:
549:
543:
541:
536:
532:
528:
524:
519:
517:
513:
508:
506:
502:
496:
494:
490:
488:
482:
473:
471:
466:
457:
451:Drug delivery
448:
446:
442:
437:
435:
430:
427:
423:
419:
415:
411:
407:
397:
394:
392:
388:
384:
380:
372:
367:
358:
356:
346:
337:
335:
326:
317:
314:
310:
306:
302:
296:
294:
290:
286:
282:
278:
276:
272:
268:
264:
260:
256:
252:
248:
244:
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426:multivalent
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28:Dendrimers
2866:203135854
2858:2366-3987
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1658:CiteSeerX
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199:chirality
152:symmetric
114:in 1981,
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4081:10573209
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527:peptides
271:pyridine
263:tosylate
191:toxicity
183:polymers
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