Development and Evaluation of 1′-Acetoxychavicol Acetate (ACA)-Loaded Nanostructured Lipid Carriers for Prostate Cancer Therapy

Bavani Subramaniam,Kein Seong Mun,Misni Misran,Norhafiza M Arshad,Sharan Malagobadan,Noor Hasima Nagoor,Shaik Nyamathulla

doi:10.3390/pharmaceutics13040439

Bavani Subramaniam, Kein Seong Mun + Show 5 more

Open Access

https://doi.org/10.3390/pharmaceutics13040439

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Journal: Pharmaceutics	Publication Date: Mar 24, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: University of Malaya

Abstract

1′-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB 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.

Highlights

IntroductionProstate cancer is the second most common cancer affecting men worldwide with approximately 1.3 million cases reported in 2018 [1]
The nanostructured lipid carrier (NLC) system exhibited ideal nanoparticle properties and was able to demonstrate the successful encapsulation of ACA and surface modification by the CXCR4 antagonist, AMD3100
The superior effectiveness of AMD-ACA-loaded NLC (ACA-NLC) in comparison to free ACA was observable in the cell culture studies

Summary

Introduction

Prostate cancer is the second most common cancer affecting men worldwide with approximately 1.3 million cases reported in 2018 [1]. Conventional chemotherapy using semisynthetic plant-derived drugs, such as docetaxel and cabazitaxel, is still regarded as the standardized method of treatment, as approved by the Food and Drug Administration (FDA) [2,3]. One such chemotherapeutic phytoconstituent discovered in recent years is. ACA has been found to induce apoptosis-mediated cell death in many cancer cell lines including prostate cancer cells with minimal potency towards normal cells [5,6].

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