Mucoadhesive thiolated quaternized chitosan as anticancer drug delivery system

Abstract

The objective of this research was to increase the mucoadhesive property of chitosan and then evaluate for its application in mucoadhesive drug delivery systems. Two mucoadhesive thiolated chitosan were synthesized by the covalent attachment of homocysteine thiolactone (HT) to chitosan (CS) and quaternized-CS (QCS) at various weight ratios of CS or QCS to HT. The modified chitosan (mCS) are characterized by NMR, FTIR, XRD, and TGA. The mucoadhesive and swelling properties of mCS were studied at pH 1.2, 4.0, and 6.4. The amount of thiol and disulfide groups immobilized on the CS influenced the polymer’s mucoadhesion positively and negatively, respectively, with the optimal CS:HT (w/w) ratio being found to be 1:0.1. The QCS-HT displayed a 6.33-fold stronger mucoadhesive property compared to that of the unmodified CS at pH 1.2. Additionally, the mCS as anticancer drug delivery systems were investigated using camptothecin (CPT) as a model anticancer drug. The microspheres of pure mCS and its polyelectrolyte complexes with alginate (ALG) and carrageenan (CR) were fabricated using electrospray ionization technique. The microspheres were characterized by SEM, particle size analyzer, FTIR, TGA, encapsulation efficiency, mucoadhesive property and in vitro drug release behavior. The CPT loaded mCS/ALG microspheres exhibited over 70% drug entrapment efficiency. The CPT-mCS/ALG microspheres displayed a 5.60-, 1.86-, and 1.55-fold stronger mucoadhesive property compared to that of the unmodified CS at pH 1.2, 4.0, and 6.4, respectively. Moreover, the obtained microspheres not only reduced the burst effect but also prolonged release of CPT within 12 h.