Surface modified poly(amido)amine dendrimers as diverse nanomolecules for biomedical applications

Abstract

The unique properties of poly(amido)amine dendrimers such as nano size, multifunctional surface, ability to encapsulate and bind the guest molecules, efficient membrane transport and shelf-life stability have made them a promising carrier in drug delivery. The two key applications of dendrimers include increasing the solubility and sustained release of molecules, and drug targeting by grafting the cell-specific ligands on the surface. Despite their potential in drug delivery, inherent cytotoxicity, reticuloendothelial system uptake and hemolysis limit their use in clinical applications. Research groups have been working on surface modification methods to mitigate these problems. Herein we present a brief discussion on current surface modification approaches to: i) increase targeting efficiency; ii) increase the cellular permeability for enhanced absorption; iii) increase gene transfection efficiency; and iv) decrease the toxicity of the dendrimers, with a few classic examples. As the knowledge of relationship between the dendrimer surface chemistry and its mode of interactions with cell membrane is developed, so do the modifications of dendrimer structure to render them nontoxic, biocompatible, biodegradable and improve their pharmacodynamic and pharmacokinetic properties. Development of multifunctional dendrimers with each functional unit imparting a distinct characteristic feature such as target cell recognition, enhanced cellular transport, reduction in reticuloendothelial system uptake and stability in in vivo environment holds a great potential for future biomedical applications.

Keywords::

• cytotoxicity
• drug delivery
• drug targeting
• gene transfection
• PAMAM dendrimers
• PD
• PK
• surface modification

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