Preparation and evaluation of chitosan-hydrophobic silica composite microspheres: Role of hydrophobic silica in modifying their properties

Biodegradable microspheres used as controlled release systems are important in pharmaceutics. Chitosan biopolymer represents an attractive alternative to other biomaterials because of its significant physicochemical and biological behaviors. Chitosan microspheres are expected to become promising carrier systems for drug and vaccine delivery, especially via oral, mucosal and transdermal routes. Controlling the swelling rate and swelling capacity of the hydrogel and improving the fragile nature of microspheres under acidic conditions are the key challenges that need to be overcome to allow the use of chitosan microspheres for controlled or sustained release specially via these non-invasive administration routes. There have been many studies on the modification of chitosan microsphere structures with cross-linkers, blends with various kinds of polymers and new organic-inorganic hybrid systems in order to obtain some improved properties. In this work, microspheres composed of chitosan and nanosized hydrophobic silica commercialized under the name Aerosil R972 were generated by a method consisting of two steps: first, preparation of a macroscopically homogeneous chitosan-hydrophobic silica dispersion by an optimized procedure, and then drying. Spray drying was the technique used here. FTIR spectroscopy, X-ray powder diffraction, differential scanning calorimetry, thermal gravimetric analysis, Scanning Electron Microscopy (SEM) and high resolution Transmission Electron Microscopy (TEM) were used to characterize the microspheres, besides acid stability, moisture sorption capacity, release properties and biological assays. The chitosan-hydrophobic silica composite microspheres showed improved thermal degradation, lower water affinity, better acid stability and ability to retard rifampicin (drug model) release under simulated gastric conditions. In vitro biocompatibility studies indicated low cytotoxicity and low capacity to activate cell production of the pro-inflammatory mediator nitric oxide, encouraging further studies on the use of the new chitosan-hydrophobic silica composite microspheres as drug carrier systems via oral or nasal routes. (C) 2013 Elsevier B.V. All rights reserved.