Gonçalves L M D, Maestrelli F, Di Cesare Mannelli L, Ghelardini C, Almeida A J, Mura P
Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Department of Chemistry, School of Sciences of Human Health, University of Florence, via Schiff 6, Sesto Fiorentino 50019, Florence, Italy.
Eur J Pharm Biopharm. 2016 May;102:41-50. doi: 10.1016/j.ejpb.2016.02.012. Epub 2016 Feb 27.
A solid lipid nanoparticle (SLN) formulation was developed with the aim of improving the oral bioavailability and the therapeutic effectiveness of glibenclamide (GLI), a poorly water-soluble drug used in the treatment of type 2 diabetes. The SLN was prepared using different lipid components (Precirol® and Compritol®) and preparation procedures. Precirol-based SLN, obtained with the emulsion of solvent evaporation technique gave the best results and was selected for drug loading. Addition of lecithin to the SLN core or PEG coating was effective in increasing the nanoparticles stability in simulated gastric solution. Both such formulations were stable after one month storage at 5±3°C, exhibited the absence of in vitro cytotoxicity, and presented a similar in vitro prolonged-release, reaching 100% release after 24h. The lecithin-containing GLI-loaded SLN formulation, selected for in vivo studies in virtue of its higher EE% than the PEG-coated formulation (70.3% vs 19.6%), showed a significantly stronger hypoglycemic effect with respect to the drug alone, in terms of both shorter onset time and longer duration of the effect. These positive results indicated that the proposed SLN approach was successful in improving GLI oral bioavailability, confirming its potential as an effective delivery system for a suitable therapy of diabetes.
开发了一种固体脂质纳米粒（SLN）制剂，旨在提高格列本脲（GLI）的口服生物利用度和治疗效果。GLI是一种用于治疗2型糖尿病的水溶性差的药物。使用不同的脂质成分（Precirol®和Compritol®）和制备程序制备了SLN。采用溶剂蒸发技术乳液法获得的基于Precirol的SLN效果最佳，并被选用于载药。向SLN核心或PEG包衣中添加卵磷脂可有效提高纳米颗粒在模拟胃液中的稳定性。这两种制剂在5±3°C下储存一个月后均稳定，无体外细胞毒性，并呈现相似的体外缓释特性，24小时后释放率达到100%。由于含卵磷脂的载GLI SLN制剂的包封率高于PEG包衣制剂（70.3%对19.6%），因此被选用于体内研究。就起效时间更短和作用持续时间更长而言，该制剂相对于单独的药物显示出显著更强的降血糖作用。这些积极结果表明，所提出的SLN方法成功提高了GLI的口服生物利用度，证实了其作为糖尿病合适治疗有效递送系统的潜力。
