Department of Biomedical Engineering, Bangladesh University of Engineering and Technology (BUET), Dhaka, Bangladesh.
Institute of Sustainability for Chemicals, Energy and Environment, Agency for Science, Technology and Research (A*STAR), Singapore 138634, Singapore.
Int J Biol Macromol. 2024 Mar;262(Pt 2):130038. doi: 10.1016/j.ijbiomac.2024.130038. Epub 2024 Feb 7.
Frequent administrations are often needed during the treatment of ocular diseases due to the low bioavailability of the existing eye drops owing to inadequate corneal penetration and rapid drug washout. Herein, sodium alginate polymannuronate (SA) nanocarriers were developed using ionic gelation method that can provide better bioavailability through mucoadhesivity and sustained drug release by binding to the ocular mucus layer. This study disproves the common belief that only the G block of SA participates in the crosslinking reaction during ionic gelation. Self-assembly capability due to the linear flexible structure of the M block, better biocompatibility than G block along with the feasibility of controlling physicochemical characteristics postulate a high potential for designing efficient ocular drug delivery systems. Initially, four crosslinkers of varied concentrations were investigated. Taguchi design of experiment revealed the statistically significant effect of the crosslinker type and concentration on the particle size and stability. The best combination was detected by analyzing the particle size and zeta potential values that showed the desired microstructural properties for ocular barrier penetration. The desired combination was SA-Ca-1 that had particle size within the optimal corneal penetration range, that is 10-200 nm (135 nm). The drug carriers demonstrated excellent entrapment efficiency (∼89 % for Ciprofloxacin and ∼96 % for Dexamethasone) along with a sustained and simultaneous release of dual drug for at least 2 days. The nanoparticles also showed biocompatibility (4 ± 0.6 % hemolysis) and high mucoadhesivity (73 ± 2 % for 0.25 g) which was validated by molecular docking analysis. The prepared formulation was able to reduce the scleral inflammation of the rabbit uveitis models significantly within 3 days. Thus, the eye drop showed remarkable potential for efficient drug delivery leading to faster recovery.
由于现有眼药水由于角膜穿透不足和药物快速冲洗而导致生物利用度低，因此在治疗眼部疾病时经常需要频繁给药。在此，使用离子凝胶化方法开发了海藻酸钠聚甘露糖醛酸（SA）纳米载体，该纳米载体可以通过与眼用粘液层结合提供更好的生物利用度，并通过粘弹性和持续药物释放来实现。该研究证明了一个普遍的观点，即在离子凝胶化过程中，只有 SA 的 G 块参与交联反应。由于 M 块的线性柔性结构，具有自组装能力，与 G 块相比具有更好的生物相容性，以及控制物理化学特性的可行性，这为设计高效的眼部药物传递系统提供了很高的潜力。最初，研究了四种浓度不同的交联剂。田口设计实验表明，交联剂类型和浓度对粒径和稳定性具有统计学显著影响。通过分析粒径和 Zeta 电位值来检测最佳组合，这些值显示出了对眼部屏障穿透的所需微观结构特性。最佳组合为 SA-Ca-1，其粒径在最佳角膜穿透范围内，即 10-200nm（135nm）。药物载体表现出良好的包封效率（环丙沙星约为 89%，地塞米松约为 96%），并能持续和同时释放至少 2 天的两种药物。纳米粒子还表现出生物相容性（4±0.6%溶血）和高粘膜粘附性（0.25g 时为 73±2%），这通过分子对接分析得到了验证。所制备的制剂能够在 3 天内显著减轻兔葡萄膜炎模型的巩膜炎症。因此，这种眼药水在高效药物输送方面显示出了显著的潜力，能够更快地恢复。
