title: Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Xiang Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: You Fu
authors.initials: YF
authors.lastname: Luo
authors.forename: Zhi Yao
authors.initials: ZY
authors.lastname: He
authors.forename: Shuang Zhi
authors.initials: SZ
authors.lastname: Li
authors.forename: Jun Ming
authors.initials: JM
authors.lastname: Li
authors.forename: Shui
authors.initials: S
authors.lastname: Yu
authors.forename: Xun
authors.initials: X
authors.lastname: Luo
authors.forename: Shi Xiang
authors.initials: SX
authors.lastname: Hou
authors.forename: Yu Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: 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
chemical_list: 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