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

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.

Natural Products for Cancer Therapy: A Review of Their Mechanism of Actions and Toxicity in the Past Decade

“…ACA in combination therapies such as with, recombinant human alpha-fetoprotein (rhAFP); and Mycobacterium indicus pranii (MIP) and cisplatin (CDDP); has exhibited significant synergistic effects against A549 human lung cancer, PC-3 human prostate cancer and 4T1 mouse mammary cell lines [74,80] via NF-ĸB inactivation. Furthermore, ACA-loaded nanostructured lipid carriers for targeted therapy to CXCR4expressing PC-3 cancer cells, demonstrated significant cytotoxicity, antimigration and anti-invasion properties in vitro [74]. Moreover, Bharadwaj and coworkers reported inhibition of colorectal cancer cell proliferation by ACA in SW480 cell line via cell cycle arrest, upregulation of p21 expression, significant reduction of cyclin D and genetic material impairment [78].…”

Recent Advances in Functional Polymer Materials for Energy, Water, and Biomedical Applications: A Review

“…Nanostructured lipid carrier (NLC) is a second-generation lipid nano-sized particle, comprising a blend of various solid and liquid lipids [178][179][180][181]. Thymoquinone (from Nigella sativa)-loaded NLC nanocarriers showed an improved bioavailability and oral delivery behavior in 4T1 bearing Balb/C mice.…”