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用于改善皮肤癌的优化瑞博西尼纳米结构脂质载体:来自皮肤渗透和皮肤动力学研究的推断

Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from skin permeation and dermatokinetic studies.

作者信息

Aldawsari Mohammed F, Kamal Mohammad Azhar, Balaha Mohamed F, Jawaid Talha, Jafar Mohammed, Hashmi Sana, Ganaie Majid Ahmad, Alam Aftab

机构信息

Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.

Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.

出版信息

Saudi Pharm J. 2024 Mar;32(3):101984. doi: 10.1016/j.jsps.2024.101984. Epub 2024 Feb 10.

Abstract

Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The , , CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.

摘要

当前的研究重点是通过局部给药途径明确开发和评估用于化疗药物瑞博西尼(RCB)的纳米结构脂质载体(NLC),以克服其固有的生物利用度缺点。尚未确定其绝对口服生物利用度,但使用基于生理的药代动力学模型预测,标准剂量的RCB(600 mg)的65.8%将主要在小肠吸收。采用溶剂蒸发法制备RCB-NLC,并采用Box-Behnken设计(BBD)优化其组成。制备的NLC平均粒径为79.29±3.53 nm,多分散指数为0.242±0.021,包封率为86.07±3.14。透射电镜分析揭示了NLC的球形形态和非聚集性质。释放研究结果表明,24小时内药物累积释放率为84.97±3.37%,显著高于RCB混悬液(RCB-SUS)。对啮齿动物(瑞士白化小鼠)进行的皮肤渗透研究表明,与RCB-SUS相比,RCB-NLC的皮肤渗透率提高了1.91倍。根据共聚焦显微镜检查结果,与RCB-SUS相比,RCB-NLC能够比RCB-SUS更深地穿透表皮膜。在皮肤动力学研究中,与RCB-SUS凝胶制剂相比,用RCB-NLC凝胶治疗时,小鼠皮肤两层中维持的RCB量更高。体外释放、体外渗透、共聚焦激光扫描显微镜和皮肤动力学数据表明,这种新型RCB制剂具有治疗皮肤癌的显著潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a7/10879011/4bfa7fdd133b/gr1.jpg

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