Tafamidis Drug Delivery Systems Based on Chitosan/Polyvinyl Alcohol Matrix

Abstract

Cardiovascular diseases retain their position as the leading cause of death globally, and according to the World Health Organization, there are 17.9 million cases of these diseases each year. Cardiac amyloidosis caused by the formation and deposition of a specific protein–polysaccharide complex–amyloid in the myocardium represents the main cause of death. The pharmaceutical molecules clinically used against amyloidosis are very limited; currently, there are only two non-selective hydrophobic agents—diflunisal and tafamidis. In addition to the non-selective mode of action of both drugs, tafamidis, with greater therapeutic efficacy, is the most expensive: the yearly course costs appr. USD 225,000. One of the possible ways of enhancing its solubility and bioavailability, decreasing the dosage with the simultaneous targeted effect, is the encapsulation of the drug into polymer (biopolymer) matrixes. In contrast to the known diflunisal delivery systems, there are no available data on the development of tafamidis delivery systems. In this study, we report, for the first time, a method for the encapsulation of tafamidis into a polymeric matrix based on the mixture of chitosan and polyvinyl alcohol (PVA). The release profile of the polymer matrix was analyzed, and no burst characteristic was demonstrated. The obtained tafamidis-loaded polymer matrixes based on biosafe and biocompatible polymers require further investigations in vitro and in vivo to evaluate their potential for clinical application.

Keywords

• cardiac amyloidosis
• chitosan
• drug delivery system
• PVA
• tafamidis