Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92 ± 3.78% and 85.78 ± 3.23%, respectively (n = 3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C + Vn or Cn + V) combination and coadministration of two single-agent-loaded PLGANPs (Cn + Vn), which was slightly higher than that of the free VCR/VRP combination (C - V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C + Vn, Cn + V, and Cn + Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo.
Song
Xiang Rong
XR
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Zheng
Yu
Y
He
Gu
G
Yang
Li
L
Luo
You Fu
YF
He
Zhi Yao
ZY
Li
Shuang Zhi
SZ
Li
Jun Ming
JM
Yu
Shui
S
Luo
Xun
X
Hou
Shi Xiang
SX
Wei
Yu Quan
YQ
D000970:Antineoplastic Agents / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004347:Drug Interactions; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014700:Verapamil / Q000008:administration & dosage* / Q000494:pharmacology; D014750:Vincristine / Q000008:administration & dosage* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004364:Pharmaceutical Preparations; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014750:Vincristine; D014700:Verapamil; C022616:thiazolyl blue; D005472:Fluorouracil