Mishra Deepak, Jain Nivrati, Rajoriya Vaibhav, Jain Ashish K
Pharmaceutics Division, ADINA Institute of Pharmaceutical Sciences, Sagar, India.
J Pharm Pharmacol. 2014 Aug;66(8):1082-93. doi: 10.1111/jphp.12235. Epub 2014 Mar 19.
The present study was focused to prepare controlled release glycyrrhizin (GL) conjugated low molecular weight chitosan nanoparticles (CS-NPs) for liver targeting. The hydrophilic antiretroviral drug lamivudine was chosen as a model drug and encapsulated within glycyrrhizin conjugated low molecular weight chitosan nanoparticles (GL-CS-NPs) for liver specificity.
First, the low molecular weight chitosan (CS) was synthesized through depolymerization method. The low molecular weight chitosan nanoparticles were prepared by inotropic gelation method. Then glycyrrhizin was conjugated with previously prepared low molecular weight chitosan nanoparticles (CS-NPs) and conjugation was confirmed by Fourier transform infrared (FT-IR) spectroscopy.
The prepared GL-CS-NPs were characterized using dynamic light scattering, transmission electron microscopy and FT-IR. The encapsulation efficiency and in-vitro drug release behaviour of drug-loaded GL-CS-NPs were studied using ultra violet spectroscopy and high performance liquid chromatographic methods. Release of lamivudine from the nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. In-vivo biodistribution study suggested the target ability of GL-CS-NPs is better and haematological study shows decline of the tissue damage in comparison with plain drug solution.
The experimental results show that the glycyrrhizin conjugated LMWC nanoparticles may be used as a potential drug delivery system with hepatocyte-targeting characteristics.
本研究旨在制备用于肝脏靶向的控释甘草酸(GL)偶联低分子量壳聚糖纳米粒(CS-NPs)。选择亲水性抗逆转录病毒药物拉米夫定作为模型药物,并将其包封于甘草酸偶联低分子量壳聚糖纳米粒(GL-CS-NPs)中以实现肝脏特异性。
首先,通过解聚法合成低分子量壳聚糖(CS)。采用离子凝胶法制备低分子量壳聚糖纳米粒。然后将甘草酸与预先制备的低分子量壳聚糖纳米粒(CS-NPs)偶联,并通过傅里叶变换红外(FT-IR)光谱法确认偶联情况。
使用动态光散射、透射电子显微镜和FT-IR对制备的GL-CS-NPs进行表征。采用紫外光谱法和高效液相色谱法研究载药GL-CS-NPs的包封效率和体外药物释放行为。拉米夫定从纳米粒中的释放呈现双相模式,即初始突释和随后的缓释。体内生物分布研究表明GL-CS-NPs的靶向能力更好,血液学研究显示与普通药物溶液相比组织损伤有所减轻。
实验结果表明,甘草酸偶联的低分子量壳聚糖纳米粒可作为一种具有肝细胞靶向特性的潜在药物递送系统。