Gajra Balaram, Dalwadi Chintan, Patel Ravi
Department of Pharmaceutics & Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, Changa, 388 421, Gujarat, India.
Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University (IIT-BHU), Varanasi, 221 005, UP, India.
Daru. 2015 Jan 21;23(1):3. doi: 10.1186/s40199-014-0087-0.
The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability.
The Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3).
The Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of -11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher.
The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer's patch or paracellular pathway which was proven by confocal microscopy.
本研究的目的是制定并研究3个独立变量对含疏水性抗真菌药物伊曲康唑的聚合物脂质杂化纳米粒（PLHNs，脂质体）优化的综合影响，并提高肠道通透性。
采用乳化溶剂蒸发法制备聚合物脂质杂化纳米粒制剂，并使用3因素3水平的Box-Behnken统计设计进行优化，得出二阶多项式方程并构建等高线图以预测响应。使用可生物降解的聚己内酯、大豆卵磷脂和聚乙烯醇制备PLHNs。选择的自变量为脂质与聚合物的比例（X1）、表面活性剂浓度（X2）、药物浓度（X3）。
Box-Behnken设计证明了所推导方程和等高线图在预测伊曲康唑PLHNs制备和优化的因变量值方面的作用。伊曲康唑PLHNs呈现纳米尺寸（210±1.8nm），包封率为83±0.6%，zeta电位为-11.7mV，并且随着渗透系数（Papp）和吸收增强率较高，还提高了伊曲康唑的通透性。
PLHNs具有可调节的粒径、表面电荷以及良好的包封效率和持续的药物释放曲线，这表明它可能是一种有前景的系统，有望通过淋巴吸收、派伊尔结的M细胞或细胞旁途径改善肠道通透性来提高生物利用度，共聚焦显微镜已证实了这一点。
