Dendrimers as anti-inflammatory agents

Abstract

His research interests include developing methodologies to complex architectures (hyperbranched macromolecules i n c l u d i n g d e n d r i m e r s , m i k t o a r m polymers, metal nanoparticles), and studying their efficacy in biological processes including drug delivery and theranostics.Pramod Avti is a Postdoctoral Fellow at Montreal Heart Institute, Montreal, Q u e b e c , C a n a d a w o r k i n g o n a collaborative project with Department of Chemistry, McGill University and Ecole Polytechnique, Montreal Canada. His current scientific interests include multifunctional nanomaterials synthesis, and their biomedical applications. In particular, his research is aimed at synthesis, interaction and conjugation of drug or gene-dendrimer conjugates to the gold nanoshells for biomedical imaging and as theranostic agents. Dendrimers constitute an intriguing class of macromolecules which find applications in a variety of areas including biology. These hyperbranched macromolecules with tailored backbone and surface groups have been extensively investigated as nanocarriers for gene and drug delivery, by molecular encapsulation or covalent conjugation. Dendrimers have provided an excellent platform to develop multivalent and multifunctional nanoconjugates incorporating a variety of functional groups including drugs which are known to be antiinflammatory agents. Recently, dendrimers have been shown to possess anti-inflammatory properties themselves. This unexpected and intriguing discovery has provided an additional impetus in designing novel active pharmaceutical agents. In this review, we highlight some of the recent developments in the field of dendrimers as nanoscale anti-inflammatory agents.Uniterms: Dendrimers. Nanocarriers. Anti-inflammatory agents. Cyclooxygenase (COX-2). Inducible nitric oxide synthase (iNOS). Pro-inflammatory cytokines.Dendrímeros constituem uma classe intrigante de macromoléculas que apresentam aplicações em diversas áreas incluindo biologia. Essas macromoléculas extremamente ramificadas com esqueleto planejado e grupos de superfície foram extensivamente investigadas como nanotransportadores de genes e de fármacos, por encapsulamento molecular ou conjugação covalente. Dendrímeros têm proporcionado uma plataforma excelente de desenvolvimento nanoconjugados multivalentes e multifuncionais incorporando uma variedade de grupos funcionais, incluindo fármacos que são conhecidos por atuarem agentes antiinflamatórios. Recentemente, os dendrímeros mostraram propriedades antiinflamatórias. Esta inesperada e intrigante descoberta tem proporcionado um impulso adicional no planejamento de novos agente farmacêuticos ativos. Nesta revisão, nós destacamos alguns dos desenvolvimentos recentes no campo dos dendrímeros como agentes antiinflamatórios em nanoescala.Unitermos: Dendrímeros. Nanotransportadores. Agentes antiinflamatórios. Ciclooxigenase (COX-2). Óxido nítrico sintase induzível (iNOS). Citocinas pró-inflamatórias.

Applications and Limitations of Dendrimers in Biomedicine

“…Figure 14 and Figure 15 exemplify several types of dendrimer—ibuprofen G4-PAMAM conjugates with ester, amide and peptide linkers. Conjugates via amine end groups have good hydrolysis stability, and ester conjugates release the active pH-dependent ibuprofen molecule from 3% (pH = 5) to 38% (pH = 8.5) [ 164 , 165 ].…”

“…PAMAM dendrimers increase the solubility of the drug more than sodium dodecyl sulfate micelles, when ibuprofen is in the ionized state, both by encapsulation in the inner cavities through hydrophobic interactions and by surface attachment through electrostatic interactions [ 165 , 166 ].…”

Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications

“…It has been shown that both the anti-inflammatory properties and the toxic effect of dendrimers are intimately related to their terminal groups, charge, and number of generations. Avti et al [97] demonstrated that PAMAM dendrimer terminated with amine (-NH2), hydroxyl (-OH) or carboxylic (-COOH) groups conjugated to glucosamine inhibit the release of cytokines. As a consequence, these dendrimers have potential as tools for various therapies, such as in rheumatoid arthritis.…”

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

“…In particular, the amine-terminated cationic polyamidoamine (PAMAM) dendrimers of various generations and their bioconjugates have been intensively studied because of their wide range of possible applications as carriers of antibodies and contrast molecules, 1,2 in protection against nonenzymatic modifications of biomacromolecules that cause various metabolic disorders, 3 in therapies for cancer, [4][5][6][7][8] and genetic and immune diseases. 9,10 The unique molecular architecture of dendrimers allows for the precise control of their size, shape, charge and targeting of ligands, and therapeutic compounds attached to surface groups, which determine their function and application. 11,12 The design and synthesis of highly effective carrier systems depend on understanding the mechanisms of delivery and internalization of modified dendrimers inside the targeted cells.…”