Pharmaceutics Research Lab, Department of Pharmaceutical Sciences, Dr. H.S Gour University, Sagar 470003, MP, India.
Int J Pharm. 2011 Dec 12;421(1):189-201. doi: 10.1016/j.ijpharm.2011.09.039. Epub 2011 Oct 1.
The objective of present research was to evaluate the potential of engineered solid lipid nanoparticles (SLNs) as vectors to bypass the blood brain barrier. Anti-cancer agent, doxorubicin (DOX) loaded SLNs were prepared and conjugated with cationic bovine serum albumin (CBSA). The formation of CBSA tethered and plain SLNs were characterized by FTIR, NMR, and TEM analyses. Physicochemical parameters such as particle size/polydispersity index and zeta-potential were also determined. Cellular uptake studies on HNGC-1 cell lines depicted almost six times enhanced uptake of ligand conjugated SLNs as compared to plain DOX solution. Furthermore, CBSA conjugated formulation was more cytotoxic as compared to free drug or unconjugated SLNs. Transendothelial studies showed maximum transcytosis ability of CBSA conjugated SLNs across brain capillary endothelial cells. In vivo pharmacokinetic parameters and biodistribution pattern demonstrated efficiency of the system for spatial and temporal delivery of DOX to brain tissues. Lastly, hematological, nephrotoxic as well as hepatotoxic data suggested CBSA conjugated formulations to be less immunogenic compared to plain formulations.
本研究旨在评估工程化固体脂质纳米粒（SLN）作为载体绕过血脑屏障的潜力。将抗癌药物阿霉素（DOX）负载的 SLN 进行制备，并与阳离子牛血清白蛋白（CBSA）进行偶联。通过傅里叶变换红外光谱（FTIR）、核磁共振（NMR）和透射电子显微镜（TEM）分析来表征 CBSA 键合和普通 SLN 的形成。还确定了物理化学参数，如粒径/多分散指数和 Zeta 电位。对 HNGC-1 细胞系的细胞摄取研究表明，与普通 DOX 溶液相比，配体偶联 SLN 的摄取增加了近六倍。此外，与游离药物或未偶联的 SLN 相比，CBSA 偶联制剂具有更高的细胞毒性。跨内皮研究表明，CBSA 偶联的 SLN 具有穿过脑毛细血管内皮细胞的最大转胞作用。体内药代动力学参数和生物分布模式表明，该系统能够有效地将 DOX 递送到脑组织，实现时空分布。最后，血液学、肾毒性和肝毒性数据表明，与普通制剂相比，CBSA 偶联制剂的免疫原性较低。
