Abstract
The present work deals with the synthesis of micro-structured biomaterials based on chitosan (CTS) for their applications as biocompatible carriers of drugs and bioactive compounds. Twelve dispersions were prepared by means of functional cross-linking with tricarballylic acid (TCA); they were characterized by Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MTDSC) and scanning electron microscopy (SEM), and their rheological properties were studied. To the best of the authors’ knowledge, no study has been carried out on the influence of CTS concentration, degree of cross-linking and drug loading on chitosan hydrogels for drug delivery systems (DDS) and is investigated herein for the first time. The influence of dispersion composition (polymer concentration and degree of cross-linking) revealed to exert a marked impact on its rheological properties, going from liquid-like to viscoelastic gels. The release profiles of a model drug, diclofenac sodium (DCNa), as well as their relationships with polymer concentration, drug loading and degree of cross-linking were evaluated. Similar to the findings on rheological properties, a wide range of release profiles was encountered. These formulations were found to display a well-controlled drug release strongly dependent on the formulation composition. Cumulative drug release under physiological conditions for 96 h ranged from 8% to 67%. For comparative purpose, Voltaren emulgel® from Novartis Pharmaceuticals was also investigated and the latter was the formulation with the highest cumulative drug release (85%). Some formulations showed similar spreadability values to the commercial hydrogel. The comparative study of three batches confirmed the reproducibility of the method, leading to systems particularly suitable for their use as drug carriers.
Highlights
Hydrogels are currently under investigation as matrices for the controlled release of bioactive molecules, in particular drugs and proteins, and for the encapsulation of living cells
We describe a highly efficient strategy for the preparation of a new batch of pH-sensitive reversible chitosan hydrogels, which are endowed with controlled release properties under physiological conditions
This study reports the preparation and use as drug carriers of a new family of eco-friendly reversible chitosan hydrogels highly compatible with biological compounds
Summary
Hydrogels are currently under investigation as matrices for the controlled release of bioactive molecules, in particular drugs and proteins, and for the encapsulation of living cells. Hydrogels are constituted by cross-linked polymer networks that have a high amount of hydrophilic domains with affinity for water. Among the favorable features of these systems, the similarity between their physical properties and those of living tissues, such as low interfacial tension with water or Polymers 2018, 10, 392; doi:10.3390/polym10040392 www.mdpi.com/journal/polymers. Polymers 2018, 10, 392 biological fluids, can be highlighted [1,2]. The elastic nature of hydrated hydrogels minimizes irritation of surrounding tissues after implantation. The low interfacial tension between the hydrogel surface and body fluid lessens protein adsorption and cell adhesion, which reduces the chances of a negative immune reaction [3]. Gels are often required to degrade under physiological conditions and lead to the disintegration of the three-dimensional structure, preferably in harmless products, to ensure good biocompatibility of the hydrogel [2]
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