Dendrimers as therapeutic agents: a systematic review

Gajbhiye, Virendra; Palanirajan, Vijayaraj K; Tekade, Rakesh K.; Jain, Narendra Kumar

doi:10.1211/jpp.61.08.0002

Cited by 169 publications

(63 citation statements)

References 112 publications

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“…Dendrimers are a new class of hyperbranched and nanoscale macromolecules that possess an array of distinctive features including a welldefined globular architecture, narrow polydispersity and tunable surface functionalities. A typical dendrimer consists of a core molecule, monomeric branches called dendrons and surface functional groups that are able to react with other compounds (7)(8)(9)(10). Poly(amidoamine) (PAMAM)…”

Section: Introductionmentioning

confidence: 99%

Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

Xue

Chen

Mao

et al. 2012

AAPS J

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Abstract. The treatment of septicemia caused by antibiotic-resistant bacteria is a great challenge in the clinic. Because traditional antibiotics inevitably induce bacterial resistance, which is responsible for many treatment failures, there is an urgent need to develop novel antibiotic drugs. Amino-terminated Poly (amidoamine) dendrimers (PAMAM-NH 2 ) are reported to have antibacterial activities. However, previous studies focused on high generations of PAMAM-NH 2 , which have been found to exhibit high toxicities. The present study aimed to clarify whether low generations of PAMAM-NH 2 could be used as novel antibacterial agents. We found that generation 2 (G2.0) PAMAM-NH 2 showed significant antibacterial effects against antibiotic-sensitive and antibiotic-resistant strains but exhibited little toxicity to human gastric epithelial cells and did not induce antibiotic resistance in bacteria. Scanning and transmission electron microscopy analyses suggested that G2.0 PAMAM-NH 2 might inhibit the growth of bacteria by destroying their cell membranes. The administration of G2.0 PAMAM-NH 2 dosedependently improved the animal survival rate of mice infected with extended-spectrum beta lactamase-producing Escherichia coli (ESBL-EC) and of animals infected with a combination of ESBL-EC and methicillin-resistant Staphylococcus aureus. A treatment regimen of 10 mg/kg of G2.0 PAMAM-NH 2 starting 12 h before inoculation followed by 10 mg/kg at 0.5 h after inoculation rescued 100% of singly infected mice and 60% of multiply infected mice. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. These findings demonstrate that the G2.0 PAMAM-NH 2 is a potential broad-spectrum and nonresistance-inducing antibiotic agent with relatively low toxicity.

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Section: Introductionmentioning

confidence: 99%

Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

Xue

Chen

Mao

et al. 2012

AAPS J

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“…37,38 While free PS was demonstrated to have a benefit ratio of 2-5:1 for tumor to normal tissue, the specific delivery could be significantly enhanced by targeting the PS to the tumor. Low solubility of PS and consequent aggregation also renders the PS to self-quench the triplet-excited state, thus reducing its efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…47 A large number of peptides have been extensively tested for tumor-specific delivery of nanoparticles, prominent among them being RGD and NGR. 38,[48][49][50] PS-dendrimer conjugates have been tested with 5-ALA, Zn(ii)-porphyrins, and pthalocyanines. 21 PS-dendrimer conjugates with polymeric micelles and other polymeric particles have also been tested.…”

mentioning

confidence: 99%

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Amreddy

Vijayashree

Adimoolam

et al. 2015

IJN

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Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21 H ,23 H -porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.

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“…Dendrimers with inherent antiretroviral activity can be synthesized by incorporating certain functional groups on their surface that can interfere with the binding of the virus to the cell. Dendrimers primarily act by blocking viral fusion to target cells and thus act as entry inhibitors in the early stages of viral infection, although secondary mechanisms of action at later stages of the viral life cycle have been reported [69][70][71]. Water-soluble dendrimers can be used as efficient carriers of antiretroviral agents which can be entrapped in the dendrimer architecture.…”

Section: Micro Particulate Drug Delivery System Journal Of Aids and Hmentioning

confidence: 99%

An Introduction to the Approaches of Novel Drug Delivery Systems for Acquired Immune Deficiency Syndrome (AIDS)

Singh¹,

Singh²

2016

Journal of AIDS and HIV infections

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Dendrimers as therapeutic agents: a systematic review

Abstract: All reports cited in this review demonstrate the use of dendrimers as medical therapeutics in different ailments. The review focuses on the current state of therapeutic potential of the dendrimer system.

Cited by 169 publications

References 112 publications

Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

An Introduction to the Approaches of Novel Drug Delivery Systems for Acquired Immune Deficiency Syndrome (AIDS)

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