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

Published on Mar 24, 2021in Pharmaceutics4.421
· DOI :10.3390/PHARMACEUTICS13040439
Bavani Subramaniam1
Estimated H-index: 1
Norhafiza M. Arshad4
Estimated H-index: 4
+ 4 AuthorsNoor Hasima Nagoor11
Estimated H-index: 11
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.
#1Sindhu C Pillai (Toyo University)H-Index: 2
#2Ankita Borah (Toyo University)H-Index: 4
Last. D. Sakthi Kumar (Toyo University)H-Index: 30
view all 6 authors...
Abstract The evolving dynamics of drug resistance due to tumor heterogeneity often creates impediments to traditional therapies making it a challenging issue for cancer cure. Breast cancer often faces challenges of current therapeutic interventions owing to its multiple complexities and high drug resistivity for example against drugs like trastuzumab and tamoxifen. Drug resistance in the majority of breast cancer is often aided by the overtly expressed P-glycoprotein (P-gp) that guides in the ra...
3 CitationsSource
#1Fadilah Sfouq Aleanizy (KSU: King Saud University)H-Index: 13
#2Fulwah Yahya Alqahtani (KSU: King Saud University)H-Index: 11
Last. Ibrahim A. Alsarra (KSU: King Saud University)H-Index: 29
view all 12 authors...
2 CitationsSource
#1Noraini Nordin (UPM: Universiti Putra Malaysia)H-Index: 6
#2Swee Keong Yeap (Ha Tai: Xiamen University)H-Index: 29
Last. Noorjahan Banu Alitheen (UPM: Universiti Putra Malaysia)H-Index: 25
view all 9 authors...
Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration...
6 CitationsSource
#1Bavani Subramaniam (UM: University of Malaya)H-Index: 1
#2Zahid H. Siddik (University of Texas MD Anderson Cancer Center)H-Index: 35
Last. Noor Hasima Nagoor (UM: University of Malaya)H-Index: 11
view all 3 authors...
Lipid-based nanoparticles for drug delivery have been employed in the development of nanomedicine for various applications. One such versatile nanoparticle type is nanostructured lipid carriers (NLCs) that include multiple combinations of lipids and drugs for diverse routes of administrations. Optimization of NLCs to achieve ideal particle size distribution, dispersion in the aqueous environment, long-term stability, drug protection ability, and targeting features is necessary for designing impr...
10 CitationsSource
#1Min Li (Zhengzhou University)H-Index: 1
#2Jianying Pei (Zhengzhou University)H-Index: 1
Last. Shuzhang Du (Zhengzhou University)H-Index: 1
view all 6 authors...
Lack of cancer-targeted delivery of chemotherapeutics is one of the major obstacles for successful cancer therapy. Nanostructured lipid carriers (NLC) have shown great promise in drug-delivery applications since they are highly scalable, biodegradable nanocarriers with high-drug-loading capacity. However, traditional method prepared NLC, the diameter of which range from 80 to 200 nm, is easily blocked and trapped in perivascular regions without further penetration. As a result, ultrasmall NLC wi...
3 CitationsSource
#1Wenpan Li (SPU: Shenyang Pharmaceutical University)H-Index: 5
#2Jia Fu (SPU: Shenyang Pharmaceutical University)H-Index: 2
Last. Haiyang Hu (SPU: Shenyang Pharmaceutical University)H-Index: 22
view all 7 authors...
Abstract Inefficient tumor accumulation and controlling drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. Inspired by the biological structure and function of low-density lipoprotein (LDL), a pH-sensitive ApoB-100/Oleic acid-DOX/NLC (AODN) nanoparticle based on nanostructured lipid carrier (NLC) was prepared in this study. The biological composition of ApoB-containing NLC nanoparticles is similar to that of LDL, which can eff...
5 CitationsSource
#1Pedzisai A. Makoni (Rhodes University)H-Index: 2
#2Kasongo Wa Kasongo (Rhodes University)H-Index: 4
Last. Roderick B. Walker (Rhodes University)H-Index: 22
view all 3 authors...
The short term stability of efavirenz-loaded solid lipid nanoparticle and nanostructured lipid carrier dispersions was investigated. Hot High Pressure Homogenization with the capability for scale up production was successfully used to manufacture the nanocarriers without the use of toxic organic solvents for the first time. Glyceryl monostearate and Transcutol® HP were used as the solid and liquid lipids. Tween® 80 was used to stabilize the lipid nanocarriers. A Box-Behnken Design was used to id...
17 CitationsSource
#1Warangkana Pornputtapitak (MU: Mahidol University)H-Index: 1
#1Warangkana Pornputtapitak (MU: Mahidol University)H-Index: 5
Last. Benchaporn Meemuk (Thailand National Science and Technology Development Agency)H-Index: 1
view all 6 authors...
: Nanostructured lipid carriers (NLCs) are used as alternative carriers for many different drug delivery administration routes. They are composed of both solid lipid and liquid lipid (oil content) with both influencing their structural properties. Amounts of liquid lipid in NLCs play a role in drug release. Effect of liquid lipid (oil content) on physiochemical characteristics of NLCs related to drug-release requires detailed investigation. Here, many techniques were performed to analyze the phy...
5 CitationsSource
#1Wen‐Bin ZhuH-Index: 1
#2Zhi‐Feng ZhaoH-Index: 1
Last. Xin ZhouH-Index: 1
view all 3 authors...
: Stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) have been found to be tightly correlated with the progression of prostate cancer (PC). In this study, we investigated the effects of an SDF-1α/CXCR4 inhibitor, AMD3100, on cell progression and metastasis potential of human PC cells. Human PC cell lines (LNCaP, PC3, and DU145) were cultured to detect SDF-1α/CXCR4, which showed higher SDF-1α and CXCR4 expression than the normal human prostate epithelial cell line, RWPE-1....
15 CitationsSource
#1Noraini Nordin (UPM: Universiti Putra Malaysia)H-Index: 6
#2Swee Keong Yeap (UPM: Universiti Putra Malaysia)H-Index: 29
Last. Noorjahan Banu Alitheen (UPM: Universiti Putra Malaysia)H-Index: 25
view all 10 authors...
Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer mod...
19 CitationsSource
Cited By0