Development of long-circulating docetaxel loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles: Optimization, pharmacokinetic, cytotoxicity and in vivo assessments

被引:27
作者
Vardhan, Harsh [1 ]
Mittal, Pooja [1 ]
Adena, Sandeep K. Reddy [1 ]
Upadhyay, Mansi [1 ]
Mishra, Brahmeshwar [1 ]
机构
[1] BHU, Indian Inst Technol, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India
关键词
Docetaxel; Quality by design; Box-Behnken design; Design of experiment; Cytotoxicity; SOLID LIPID NANOPARTICLES; BY-DESIGN QBD; PLGA-NANOPARTICLES; FORMULATION VARIABLES; DRUG-RELEASE; DELIVERY; VITRO; QUALITY; PARAMETERS; SIZE;
D O I
10.1016/j.ijbiomac.2017.05.125
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long-circulating nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett-Burman (PBD) and Box-Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39 +/- 0.85%. The particle size of the nanoparticles was found to be 260 +/- 2.85 nm, while the zeta potential was-18 +/- 2.12 mV, indicating more stable particles. SEM, TEM, and AFM were used for characterization of surface morphology and the physicochemical characters of NPs. A pharmacokinetic evaluation carried out intravenous administration in healthy Charles Foster rats displayed enhanced systemic bioavailability and plasma drug concentration. The in vivo-in silico assessment by GastroPlus (TM) showed good prediction accuracy and presented best-fit model. Nanoparticles were also studied for stability testing and were found to be stable concerning their drug content and physical characters. In vitro cytotoxicity was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. Anti-cancer studies of optimized NPs showed a significant increase in efficacy as observed by relative tumor volume up to 30 days. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:791 / 801
页数:11
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