Kinetics and Controlled Localized Drug Release From Chitosan-Ascorbic Acid Complex Based Microparticles For Potential Treatment of Triple Negative Breast Cancer

Nwazojie, Chukwudalu Clare (2018-12-10)

Main Thesis


Triple Negative Breast Cancer (TNBC) is the most predominant form of breast cancer among women of African descent. Breast cancers affects many women globally and the existing treatment methods, such as chemotherapy, have not been very effective due to the side effects on normal cells. A localized method of drug delivery has been envisaged as an ideal way of selectively killing the cancer cells while reducing the side effects on normal cells. Chitosan (CS) has been shown to be an effective drug carrier. However, it requires internalization by cells to potentiate the effect of the drug upon drug release inside the cell. Ascorbic acid (AA) is transported into many cells through the sodium-dependent vitamin c transporters (SVCTs) on the surface of the cells. Thus, chemically complexing CS with AA and using this to encapsulate drugs may facilitate the entry of drug-loaded microparticles of CS-AA complexes into cancer cells and subsequent drug release inside the cells. In this study, we explore the CS-AA complexes to facilitate the cellular internalization of CS-AA microspheres used to encapsulate Prodigiosin (PG) and Paclitaxel (PTX). Following the production of CS-AA complexes, single emulsion (water/oil) technique was used to synthesize CS-AA microparticles with encapsulated PG at varying concentrations. The microparticles are characterized using FTIR, DSC, TGA, UV-Vis and SEM. The Higuchi and Korsmeyer-Peppas kinetic models were deployed to study the drug release kinetics. This study demonstrates that microparticles of CS-AA complexes with encapsulated PG and PTX can be synthesized for potential targeting of breast cancer tumours.