PDF(Pubmed)
Abstract：
Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson\'s disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD.
摘要：
溴隐亭(BCR)由于其低溶解度和延长的首过代谢而在口服给药时呈现差的生物利用度。这在将其用作治疗帕金森病（PD）的有效治疗方法方面提出了重大挑战。利用脂质纳米颗粒可以是克服BCR生物利用度限制的有希望的方法。研究工作的目的是使用Box-Behnken设计（BBD）开发和评估装载溴隐亭的固体脂质纳米颗粒（BCR-SLN）和装载溴隐亭的纳米结构脂质载体（BCR-NLC）。使用高压均质方法开发了BCR-SLN和BCR-NLCs。对制备的纳米粒子进行了粒径表征(PS),多分散指数(PDI)，和截留效率(EE)。体外药物释放，细胞毒性研究，体内血浆药代动力学，和脑分布研究评估了优化的脂质纳米颗粒。优化的BCR-SLN的PS为219.21±1.3nm，PDI为0.22±0.02，EE为72.2±0.5。PS,PDI,发现优化的BCR-NLC制剂的EE和EE分别为182.87±2.2、0.16±0.004和83.57±1.8。BCR-SLN和BCR-NLC的体外释放曲线显示出双相模式，立即释放,然后由于持续释放而落后。此外，药代动力学研究表明,与BCR溶液相比,优化的BCR-SLN和BCR-NLC制剂均可改善药物的血浆和脑生物利用度.根据研究结果,可以得出结论，负载BCR的脂质纳米粒可以通过增强药物的BBB渗透并有助于改善BCR在PD管理中的生物利用度和治疗功效而成为有前途的载体。
