Development and evaluation of 1 `-acetoxychavicol acetate (ACA)-loaded nanostructured lipid carriers for prostate cancer therapy

Subramaniam, Bavani and Arshad, Norhafiza M. and Malagobadan, Sharan and Misran, Misni and Nyamathulla, Shaik and Mun, Kein Seong and Nagoor, Noor Hasima (2021) Development and evaluation of 1 `-acetoxychavicol acetate (ACA)-loaded nanostructured lipid carriers for prostate cancer therapy. Pharmaceutics, 13 (4). ISSN 1999-4923, DOI https://doi.org/10.3390/pharmaceutics13040439.

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Abstract

1 `-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF- signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.

Item Type: Article
Funders: Universiti Malaya (RU030-2014C), Center for Research in Biotechnology for Agriculture (CEBAR) Research University grant (TU002F-2018)
Uncontrolled Keywords: Nanostructured lipid carrier; 1′ -acetoxychavicol acetate; AMD3100; Targeted delivery; Prostate cancer
Subjects: R Medicine > RM Therapeutics. Pharmacology
T Technology > TA Engineering (General). Civil engineering (General)
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms Zaharah Ramly
Date Deposited: 29 Mar 2022 02:24
Last Modified: 29 Mar 2022 02:24
URI: http://eprints.um.edu.my/id/eprint/28614

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