pH-sensitive Nanoformulation of Acetyl-11-Keto-beta-Boswellic Acid (AKBA) as a Potential Antiproliferative Agent in Colon Carcinogenesis (In Vitro and In Vivo)

Abstract

Background Developing a drug delivery system that can transport a higher concentration to the target cells can improve therapeutic efficacy. This study aimed to develop a novel delivery system for Acetyl-11-Keto-beta-Boswellic Acid (AKBA) using chitosan-sodium alginate-calcium chloride (CS-SA-CaCl₂) nanoparticles. The objectives were to evaluate the antiproliferative activity of these nanoparticles against colorectal cancer (CRC) cells and to improve the bioavailability and therapeutic efficacy of AKBA. Results With an extraction efficiency of 12.64%, AKBA was successfully extracted from the gum resin of B. serrata. The nanoparticle delivery system exhibited superior cytotoxicity against HT29 cells compared to free AKBA, AKBA extract (BA-Ex), and 5-FU. Furthermore, the nano formulation (nano-BA-Ex), induced apoptosis in HT29 cells more effectively than the other treatments. In vivo results showed that nanoformulation inhibited chemically induced colon tumorigenesis in mice and significantly reduced the number of aberrant crypt foci (ACFs). Conclusions The developed CS-SA-CaCl₂ nanoparticles loaded with AKBA extract exhibit potential as a potent drug delivery mechanism for the colorectal cancer model. Nano-BA-Ex is a promising strategy for enhancing the solubility, bioavailability, and therapeutic efficacy of BA derivatives. With its multiple effects on cancer cells and controlled drug release through nanocapsules, nano-BA-Ex stands out as a compelling candidate for further preclinical and clinical evaluation in CRC therapy.