Phongpradist Rungsinee, Thongchai Wisanu, Thongkorn Kriangkrai, Lekawanvijit Suree, Chittasupho Chuda
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand.
Polymers (Basel). 2022 Jan 22;14(3):443. doi: 10.3390/polym14030443.
Curcumin is one of the most promising natural therapeutics for use against Alzheimer's disease. The major limitations of curcumin are its low oral bioavailability and difficulty in permeating the blood-brain barrier. Therefore, designing a delivery system of curcumin to overcome its limitations must be employed. KLVFF, a peptide known as an amyloid blocker, was used in this study as a targeting moiety to develop a targeted drug delivery system. A prototype of transnasal KLVFF conjugated microemulsions containing curcumin (KLVFF-Cur-ME) for the nose-to-brain delivery was fabricated. The KLVFF-Cur-ME was developed by a titration method. A conjugation of KLVFF was performed through a carbodiimide reaction, and the conjugation efficiency was confirmed by FTIR and DSC technique. KLVFD-Cur-ME was characterized for the drug content, globule size, zeta potential, and pH. A transparent and homogeneous KLVFF-Cur-ME is achieved with a drug content of 80.25% and a globule size of 76.1 ± 2.5 nm. The pH of KLVFF-Cur-ME is 5.33 ± 0.02, indicating non-irritation to nasal tissues. KLVFD-Cur-ME does not show nasal ciliotoxicity. An ex vivo diffusion study revealed that KLVFF-Cur-ME partitions the porcine nasal mucosa through diffusion, following the Higuchi model. This investigation demonstrates the successful synthesis of a bifunctional KLVFF-Cur-ME as a novel prototype to deliver anti-A aggregation via an intranasal administration.
姜黄素是用于对抗阿尔茨海默病最有前景的天然治疗药物之一。姜黄素的主要局限性在于其口服生物利用度低以及难以透过血脑屏障。因此,必须采用设计姜黄素递送系统来克服其局限性。KLVFF,一种被称为淀粉样蛋白阻断剂的肽,在本研究中用作靶向部分以开发靶向药物递送系统。制备了一种用于鼻脑递送的含姜黄素的经鼻KLVFF共轭微乳剂(KLVFF-Cur-ME)原型。KLVFF-Cur-ME通过滴定法制备。通过碳二亚胺反应进行KLVFF的共轭,并通过傅里叶变换红外光谱(FTIR)和差示扫描量热法(DSC)技术确认共轭效率。对KLVFD-Cur-ME进行药物含量、球粒大小、zeta电位和pH值表征。获得了一种透明且均匀的KLVFF-Cur-ME,其药物含量为80.25%,球粒大小为76.1±2.5nm。KLVFF-Cur-ME的pH值为5.33±0.02,表明对鼻组织无刺激性。KLVFD-Cur-ME未显示鼻纤毛毒性。体外扩散研究表明,KLVFF-Cur-ME通过扩散穿过猪鼻黏膜,符合Higuchi模型。本研究证明成功合成了一种双功能KLVFF-Cur-ME,作为通过鼻内给药递送抗A聚集物的新型原型。