Achmad Nurafni Annisa, Tuna Rachmatya W, Kurniawan Irfan, Asaf Muhammad Bisfain, Rahman Latifah, Manggau Marianti A, Dominguez-Robles Juan, Aswad Muhammad, Permana Andi Dian
Faculty of Pharmacy, Hasanuddin University, Makassar 90245, South Sulawesi, Indonesia.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, Seville 41012, Spain.
Langmuir. 2025 Jan 14;41(1):314-328. doi: 10.1021/acs.langmuir.4c03530. Epub 2024 Dec 23.
Alzheimer's disease (ALZ) is a neurodegenerative disease that damages neuronal cells and causes decline in cognitive abilities. Administration of cholinesterase inhibitor compounds is the primary choice in the treatment of ALZ, one of which is rivastigmine (RVT). Several routes of administration of RVT are available, such as oral and transdermal. However, in the oral route, RVT has low bioavailability, undergoes first-pass metabolism, and the presence of the blood-brain barrier (BBB) reduces the therapeutic concentration of RVT. The transdermal route is nonselective target in the brain. This study aims to combine thermosensitive mucoadhesive gel (TG) and lipid microspheres (LM) as a drug delivery system to improve the efficacy of RVT. Combining these will prevent systemic side effects of RVT and increase drug concentration in the brain. LM was formulated with varying concentrations of Compritol polymer. The results of LM evaluation showed the values of particle size, PDI, and %EE and %DL were 8.519 μm, 0.018 ± 0.004, 72.54%, and 76.43%, respectively. The TG formulation can provide a liquid form at room temperature (25 °C) and a gel at nasal temperature (35 °C). Hemolytic and HET-CAM tests confirmed TG RVT LM's safety for use. studies showed controlled and sustained release of TG RVT LM, and studies showed TG RVT LM a higher pharmacokinetic profile in the brain than oral formulations and injections. The was found to be 7.05 ± 0.55 μg/cm, was 24 h, and AUC, which is related to the effectiveness of brain targeting, was 225.73 μg/cm. In conclusion, this study shows the successful development of TG RVT LM, as evidenced by improved drug delivery to the brain, which is characterized by higher concentrations of RVT in the brain compared with oral and injectable RVT, this delivery system shows potential as a future treatment for Alzheimer's disease.
阿尔茨海默病（ALZ）是一种神经退行性疾病，会损害神经元细胞并导致认知能力下降。给予胆碱酯酶抑制剂化合物是治疗ALZ的主要选择，其中之一是卡巴拉汀（RVT）。RVT有几种给药途径，如口服和透皮给药。然而，在口服途径中，RVT的生物利用度低，会经历首过代谢，并且血脑屏障（BBB）的存在会降低RVT的治疗浓度。透皮途径在大脑中是非选择性靶向的。本研究旨在将热敏性粘膜粘附凝胶（TG）和脂质微球（LM）结合作为药物递送系统，以提高RVT的疗效。将两者结合将防止RVT的全身副作用并增加大脑中的药物浓度。LM是用不同浓度的Compritol聚合物配制的。LM评估结果显示粒径、PDI、%EE和%DL的值分别为8.519μm、0.018±0.004、72.54%和76.43%。TG制剂在室温（25°C）下可呈液体形式，在鼻腔温度（35°C）下呈凝胶形式。溶血和HET-CAM试验证实了TG RVT LM使用的安全性。研究表明TG RVT LM具有控释和缓释特性，研究表明TG RVT LM在大脑中的药代动力学特征优于口服制剂和注射剂。发现Cmax为7.05±0.55μg/cm，Tmax为24小时，与脑靶向有效性相关的AUC为225.73μg/cm。总之，本研究表明TG RVT LM的成功开发，其证据是改善了药物向大脑的递送，其特征是与口服和注射用RVT相比，大脑中RVT的浓度更高，这种递送系统显示出作为未来治疗阿尔茨海默病的潜力。
