Development of Biocompatible Nanoparticles of Tizanidine Hydrochloride in Orodispersible Films: In vitro Characterization, Ex vivo Permeation, and Cytotoxic Study on Carcinoma Cells

Abstract

Background: The main limitations of the therapeutic effectiveness of tizanidine hydrochloride (TNZ) are its low bioavailability due to its tendency to undergo first-pass metabolism and short biological half-life. These factors make it an ideal candidate for formulating orally disintegrating films. Methods: The fast-dissolving film of TNZ HCl was prepared by the solvent-casting method and characterized using scanning electron microscopy, FTIR and XRD, and evaluated for critical quality attributes for this type of dosage forms such as disintegration time, tensile strength, drug content, dissolution, and ex-vivo permeability. In vitro cytotoxicity studies were also conducted on cancer cell lines to confirm cytotoxic effect. Objective: The present study was aimed to prepare nanoparticles of tizanidine hydrochloride using biodegradable polymers and loading them on orodispersible films to obtain a sustained release dissolution profile with improved permeability and further study the cytotoxicity on A549 lung carcinoma cells, MCF7 breast cancer cells and HOP 92 non-small lung adenocarcinoma cells. Results: The polymeric matrix containing the drug provided a rapid disintegration time varying between 7±2 and 30±2 seconds, adequate tensile strength between 1.4 and 11.25 N/mm2, and improved permeability through porcine buccal mucosa when compared to the reference product. Conclusion: A study of cytotoxic effect on the MCF-7 breast cancer cells and A549 lung carcinoma cells revealed that tizanidine hydrochloride nanoparticles at 2.3 mg/film exhibited an IC50 value of 65.1 % cytotoxicity on MCF-7, approximately 100% on HOP92, and 83.5 % on A549 lung carcinoma cells, thus paving the way for a new paradigm of research for cytotoxic study on MCF-7, HOP92 and A549 cell lines using the subject drug model prepared as oral films or biodegradable nanoparticles in oral films for site-specific targeting.