Drug Delivery Laboratory, TIFAC Centre of Relevance and Excellence in NDDS, Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, India.
Drug Dev Ind Pharm. 2013 May;39(5):733-43. doi: 10.3109/03639045.2012.694889. Epub 2012 Jun 12.
The present study was aimed at developing colloidal formulations like solid lipid nanoparticles (SLN) and nanosuspension (NS) for improving bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor which displays poor oral bioavailability. SLNs were prepared by solvent injection method while NS was prepared by pearl milling method. The prepared formulations were characterized for physicochemical parameters such as particle size, ζ potential, drug content, X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC). Pharmacokinetic and biodistribution studies were performed in mice to evaluate in vivo fate of the formulations. The SLNs showed particle size of 267 ± 18 nm and entrapment efficiency of 73.5 ± 2.12%. The particle size obtained for NS was 393 ± 13 nm against 710 ± 70 μm for bulk drug, which led to significant improvement in saturation solubility. DSC and XRD studies of NS and SLN showed reduction in crystallinity while in vitro studies showed improved dissolution rate in both cases. Pharmacokinetics studies of orally administered formulations in mice exhibited higher plasma concentration compared to plain drug. Biodistribution studies showed higher accumulation of drug in liver, kidneys, intestine and stomach. The higher concentration of AD in liver after 24 hr highlights its potential advantage for effective treatment of chronic hepatitis infection. The relative bioavailability for adefovir NS and SLN were 52.46% and 78.23% respectively compared to 34.34% bioavailability obtained after administration of adefovir micro suspension (AMS), indicating suitability of both nanoparticulate formulations for improving bioavailability. SLNs were found to performed better as compared to NS for improving the bioavailability of AD.
本研究旨在开发胶体制剂，如固体脂质纳米粒（SLN）和纳米混悬剂（NS），以提高阿德福韦酯（AD）的生物利用度。AD 是一种核苷逆转录酶抑制剂，口服生物利用度差。SLN 采用溶剂注入法制备，NS 采用珠磨法制备。对所制备的制剂进行理化参数如粒径、ζ电位、药物含量、X 射线衍射（XRD）、差示扫描量热法（DSC）的表征。在小鼠中进行药代动力学和生物分布研究，以评估制剂的体内命运。SLN 粒径为 267±18nm，包封效率为 73.5±2.12%。NS 的粒径为 393±13nm，而原料药的粒径为 710±70μm，这导致了饱和溶解度的显著提高。NS 和 SLN 的 DSC 和 XRD 研究表明结晶度降低，体外研究表明两种情况下的溶解速率均有所提高。口服给予小鼠制剂的药代动力学研究表明，与普通药物相比，血浆浓度更高。生物分布研究表明，药物在肝脏、肾脏、肠道和胃中的积累更高。24 小时后肝脏中 AD 的浓度更高，这突出了其在有效治疗慢性肝炎感染方面的潜在优势。与阿德福韦微悬浮（AMS）给药后获得的 34.34%生物利用度相比，阿德福韦 NS 和 SLN 的相对生物利用度分别为 52.46%和 78.23%，表明这两种纳米颗粒制剂均适合提高生物利用度。与 NS 相比，SLN 更能提高 AD 的生物利用度。
