title: Improved oral bioavailability and anticancer efficacy on breast cancer of paclitaxel via Novel Soluplus(®)-Solutol(®) HS15 binary mixed micelles system.
abstract: The aim of this study was to develop a novel drug delivery system using two biocompatible copolymers of Solutol(®)HS15 and Soluplus(®) to improve solubility, oral bioavailability and anticancer activity of paclitaxel (PTX). The PTX-loaded mixed micelles (PTX-M) were prepared by ethanol thin-film hydration method. The optimal PTX-M were provided with small size (164.8±2.0nm) and spherical shape at ratio of 1: 3 (Solutol(®)HS15: Soluplus(®)), thus increasing the solubility to 15.76±0.15mg/mL in water. The entrapment efficiency and drug loading of PTX-M were 98.48±0.91% and 10.59±0.09% respectively. In vitro release study indicated a sustained release of PTX-M. Transcellular transport study showed that the efflux ratio were decreased by 89.72% dramatically in Caco-2 cell transport models, and the pharmacokinetics study of PTX-M compared with PTX, showed a 3.68-fold increase in relative oral bioavailability, indicating the mixed micelles may promote absorption in the gastrointestinal tract. In addition, the MTT assay demonstrated that the IC50 value of PTX-M was reduced by 40.21% (PTX-M: 22.6±2.1μg/mL, PTX: 37.8±1.4μg/mL), and in vivo anti-tumor study (15days' therapy) showed PTX-M achieved higher anti-tumor efficacy (57.66%) compared with PTX (41.13%). Furthermore, a gastrointestinal safety assay also provided the reliability and safety of PTX-M. Collectively, these findings present an oral micelle formulation with increased solubility, oral bioavailability and anticancer activity of PTX.
authors: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China; College of Pharmacy, Jiangsu University, Jiangsu, Zhenjiang 212013, China.
authors: Jian
authors: J
authors: Hou
authors: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China.
authors: E
authors: E
authors: Sun
authors: College of Pharmacy, Jiangsu University, Jiangsu, Zhenjiang 212013, China.
authors: Congyong
authors: C
authors: Sun
authors: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China.
authors: Jing
authors: J
authors: Wang
authors: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China; College of Pharmacy, Jiangsu University, Jiangsu, Zhenjiang 212013, China.
authors: Lei
authors: L
authors: Yang
authors: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China; College of Pharmacy, Jiangsu University, Jiangsu, Zhenjiang 212013, China. Electronic address: jxiaobin2005@hotmail.com.
authors: Xiao-Bin
authors: XB
authors: Jia
authors: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China.
authors: Zhen-Hai
authors: ZH
authors: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D065546:Drug Liberation; D008297:Male; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D051381:Rats; D013229:Stearic Acids / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011145:Polyvinyls; D013229:Stearic Acids; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D017239:Paclitaxel
keywords: Anti-tumor; Caco-2 monolayer; HE staining; Micelles; Oral bioavailability; Paclitaxel; Soluplus(®); Solutol(®)HS15