Chemically Modified Gelatin as Biomaterial in the Design of New Nanomedicines

Rita      Lopez-Cebral; M.      Martin-Pastor; Jenny      Evelin Parraga; Giovanni      Konat Zorzi; Begona      Seijo; Alejandro      Sanchez

Abstract

The synthesis of new polymers has led to dramatic enhancements in the medical field. In particular, new chemical entities provided new prospects in tissue engineering, cellular therapy and drug delivery. However, significant efforts still need to be taken in consideration in order to achieve diverse clinical applications in these fields, which is challenging because of the lack of suitable materials with desired microstructure, permeability, degradation rates, products, and suitable mechanical properties. For these reasons some chemical strategies are focused in back to the nature approaches or, in other words, in improving the properties of natural polymers by chemical modifications.

We report that by using a simple chemical modification technique we can obtain new biomaterials, specifically suitable for biomedical applications. Concretely, we describe the chemical modification of gelatin and the suitable characteristics of the modified protein to develop new nanomedicines. This protein was selected because of its enormous potential in biomedicine, which is currently limited due to the difficulty of its use without toxic chemical crosslinkers. The modification of the protein was based on the transformation of the carboxylic group into amido groups after their reaction with polyamines, leading to a positively charged biopolymer. To cationize the gelatin two polyamines where used: ethylenediamine and spermine, the latter being one of the endogenous polyamines which has a very positive influence over cells. This modification was monitored by physico-chemical techniques such as NMR, spectrophotometry and potentiometry.

With the most promising modified gelatins we were able to develop nanoparticles using the ionotropic gelation technique. In order to determine the ability of these new nanosystems to associate bioactive molecules we selected a model plasmid DNA. The developed nanosystems were characterized corroborating their ability to associate the genetic material. In conclusion, we were able to obtain a semi-synthetic biomaterial with tunable physico-chemical properties, which can be used to develop new nanosystems with the ability to associate genetic material. We therefore propose that the gelatin, with its chemical modification, provide a unique biomaterial for the development of new nanomedicines.

Keywords: Chemically modified protein, gelatin, nanoparticles, nanomedicines, gene delivery, polymers, tissue engineering, cellular therapy, drug delivery, chemical crosslinkers, biopolymer, ethylenediamine, spermine, NMR, spectrophotometr, potentiometry