Date of Award

2023

Document Type

Dissertation

Degree Name

Philosophy (Ph.D)

Department

Pharmaceutical Sciences

First Advisor

Emilio Squillante

Second Advisor

Ketan Patel

Third Advisor

Bhagwan Rohera

Abstract

Albendazole (ABZ) is a broad-spectrum anthelminthic drug with poor aqueous solubility. It has also been repurposed to treat various types of cancers. One of the objectives of this research is to prepare solid dispersion of ABZ to improve the solubility and dissolution rate using supercritical fluid (SCF) technology. The other objective is to repurpose ABZ against colorectal cancer (CC) by formulating ABZ nanosuspension (NS), also known as nanocrystal. There are various methods to prepare solid dispersions, but SCF using carbon dioxide (CO2) becomes attractive due to its own advantages, including non-toxic, low temperature required, low cost and environmentally friendly without organic solvent. We successfully optimized and prepared ABZ solid dispersion with Kollidon VA64 using SCF technology, and achieved improved saturation solubility and dissolution rate at both stomach and intestine pH. However, the MDCK permeability study revealed low to medium permeability of ABZ in solid dispersion. Therefore, instead of systemic effect as anthelminthic drug, we tried to repurpose ABZ against colorectal cancer by formulating ABZ NS to have local effect. ABZ NS was prepared by dual centrifugation method using Kollidon VA64 and sodium lauryl sulphate (SLS) as stabilizer and surfactant. The optimized NS achieved nano-scaled particle size, and was stable for at least 6 months in room temperature. The in vitro cytotoxicity studies and 3D tumor spheroids assay on colon cancer cells HT-29 and HCT-116 indicated its anti-colorectal cancer effect.

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