Development of Ph-Sensitive Biomaterial-Based Nanocomposite for Highly Controlled Drug Release

Combining non-toxic biomaterials to obtain high effective hybrids is a promising approach in medicine and drug delivery. This study aims to combine the biomaterial with different swelling behavior to attain high controllable release. Hydroxyapatite (HA) nanoparticles do not possess swelling properties and are stable in different pH solutions and therefore can affect the swelling behavior of hydrogels. In this study, HA was used to prevent the unwanted sudden release of chitosan-based hybrids (CTS) in acidic media. CTS being soluble in acidic pHs causes drug release as it dissolves, resulting in burst release behavior. The experiments confirmed that the introduction of HA remarkably reduced the swelling rate leading to a decrease in the release rate (approximately 38 to 73%) independently of the pH. Indeed, the release rate was controlled by modifying the amount of HA. The kinetic investigations indicated the release mechanisms were changed from dissolution in CTS/MMt to diffusion in CTS/MMt/HA by introducing HA, which is compatible with the swelling ratio reduction. As well as CTS/MMt, HA grafted samples showed high encapsulation efficiency (>96%) and pH-sensitive properties. The biocompatibility of Metronidazole-loaded nanocomposites was confirmed by the cytotoxicity tests on the human nasopharyngeal carcinoma L929 cells.