Department of Pharmaceutics, Faculty of Pharmacy, Port Said University, Port Said 42515, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Int J Pharm. 2024 Dec 25;667(Pt A):124865. doi: 10.1016/j.ijpharm.2024.124865. Epub 2024 Oct 26.
The clinical implication of clarithromycin (CLT) is compromised owing to its poor solubility and, subsequently, bioavailability, unpalatable taste, rapid metabolism, short half-life, frequent dosing, and adverse effects. The present investigation provides an innovative sustained-release oral drug delivery strategy that tackles these challenges. Accordingly, CLT was loaded into a cubosome, a vesicular system with a bicontinuous cubic structure that promotes solubility and bioavailability, provides a sustained release system combating short half-life and adverse effects, masks unpleasant taste, and protects the drug from destruction in gastrointestinal tract (GIT). Nine various formulas were fabricated using the emulsification method. The resulting vesicles increased the encapsulation efficiency (EE %) from 57.64 ± 0.04 % to 96.80 ± 1.50 %, the particle size (PS) from 147.30 ± 21.77 nm to 216.61 ± 5.37 nm, and the polydispersity index (PDI) values ranged from 0.117 ± 0.024 to 0.278 ± 0.073. The zeta potential (ZP) changed from -20.65 ± 2.01 mV to -33.98 ± 2.60 mV. Further, the release profile exhibited a dual release pattern within 24 h., with the percentage of cumulative release (CR %) expanding from 30.06 ± 0.42 % to 98.49 ± 2.88 %, optimized formula was found to be CC9 with EE % = 96.80 ± 1.50 %, PS = 216.61 ± 5.37 nm, ZP = -33.98 ± 2.60 mV, PDI = 0.117 ± 0.024, CR % = 98.49 ± 2.88 % and IC50 of 0.74 ± 0.19 µg/mL against HepG-2 cells with scattered unilamellar cubic non-agglomerated vesicles. Additionally, it exhibited higher anti-MRSA biofilm, relative bioavailability (2.8 fold), and anti-inflammatory and antimicrobial capacity against Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus compared to free CLT. Our data demonstrate that cubosome is a powerful nanocarrier for oral delivery of CLT, boosting its biological impacts and pharmacokinetic profile.
克拉霉素（CLT）的临床意义受到其较差的溶解度和生物利用度、不良口感、快速代谢、半衰期短、频繁给药和不良反应的影响。本研究提供了一种创新的缓释口服药物递送策略，可解决这些挑战。因此，将 CLT 装载到立方体内，立方体内是一种具有双连续立方结构的囊泡系统，可提高溶解度和生物利用度，提供缓释系统以对抗半衰期短和不良反应，掩盖不良口感，并保护药物免受胃肠道（GIT）破坏。使用乳化法制备了九个不同的配方。结果囊泡增加了包封效率（EE%）从 57.64±0.04%至 96.80±1.50%，粒径（PS）从 147.30±21.77nm 至 216.61±5.37nm，多分散指数（PDI）值范围为 0.117±0.024 至 0.278±0.073。Zeta 电位（ZP）从-20.65±2.01mV 变为-33.98±2.60mV。此外，释放曲线在 24 小时内呈现出双重释放模式，累积释放百分比（CR%）从 30.06±0.42%扩展到 98.49±2.88%，优化的配方为 EE%=96.80±1.50%，PS=216.61±5.37nm，ZP=-33.98±2.60mV，PDI=0.117±0.024，CR%=98.49±2.88%和对 HepG-2 细胞的 IC50 为 0.74±0.19µg/mL，细胞内有分散的单室立方非聚集囊泡。此外，与游离 CLT 相比，它对耐甲氧西林金黄色葡萄球菌生物膜具有更高的抗药性、相对生物利用度（2.8 倍）以及对铜绿假单胞菌、大肠杆菌、枯草芽孢杆菌和金黄色葡萄球菌的抗炎和抗菌能力。我们的数据表明，立方体制剂是 CLT 口服递送的有效纳米载体，可提高其生物学影响和药代动力学特征。
