Hydrogels of Polycationic Acetohydrazone-Modified Phosphorus Dendrimers for Biomedical Applications: Gelation Studies and Nucleic Acid Loading

Evgeny K Apartsin,Serge Mignani,Alya G Venyaminova,Audrey Malrin-Fournol,Alina E Grigoryeva,Jean-Pierre Majoral,Elena I Ryabchikova,Anne-Marie Caminade

doi:10.3390/pharmaceutics10030120

Abstract

In this work, we report the assemblage of hydrogels from phosphorus dendrimers in the presence of biocompatible additives and the study of their interactions with nucleic acids. As precursors for hydrogels, phosphorus dendrimers of generations 1–3 based on the cyclotriphosphazene core and bearing ammonium or pyridinium acetohydrazones (Girard reagents) on the periphery have been synthesized. The gelation was done by the incubation of dendrimer solutions in water or phosphate-buffered saline in the presence of biocompatible additives (glucose, glycine or polyethylene glycol) to form physical gels. Physical properties of gels have been shown to depend on the gelation conditions. Transmission electron microscopy revealed structural units and well-developed network structures of the hydrogels. The hydrogels were shown to bind nucleic acids efficiently. In summary, hydrogels of phosphorus dendrimers represent a useful tool for biomedical applications.

Highlights

Local drug delivery is a powerful approach to treat a wide number of diseases, including cancer, inflammation and so forth
Cyclotriphosphazene core-based phosphorus dendrimers bearing trimethylammonium acetohydrazone (Girard T reagent) or pyridinium acetohydrazone (Girard P reagent) moieties on the periphery were synthesized by grafting of corresponding hydrazides onto the surface of aldehyde-terminated dendrimers upon mild acid catalysis [22]
In this work, physical hydrogels of phosphorus dendrimers containing biocompatible additives have been obtained for the first time

Summary

Introduction

Local drug delivery is a powerful approach to treat a wide number of diseases, including cancer, inflammation and so forth. Dendrimers—symmetric hyperbranched polymers—are considered prospective tools for nanomedicine [5]. They have been recently used as building blocks for hydrogels. One dendrimer-containing gel drug, Vivagel®, has been approved by the US FDA for the use in condom lubricants to prevent the HIV infection [8,9]. It is subjected for clinical trials as a therapeutic to treat bacterial vaginosis as well [10,11]. This recent success encourages the development of new dendrimer-containing constructions and materials for innovative medicine

Methods

Results

Conclusion