Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy; Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria.
Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy.
Int J Pharm. 2022 Jun 25;622:121905. doi: 10.1016/j.ijpharm.2022.121905. Epub 2022 Jun 10.
Indomethacin (IND) is topically administered for the treatment of the anterior segment diseases such as conjunctivitis, uveitis, and inflammation prevention for post-cataract surgery, as well as posterior segment diseases as macular edema. Currently IND is available as 0.1% w/v hydroxypropyl-β-cyclodextrin-based eye drop formulation and its bioavailability is limited by several drawbacks such as the nasolacrimal duct draining, the reflex blinking and the low volume of the conjunctival sac. In this study, chitosan (CS)/sulfobutylether-β-cyclodextrin (SBE-β-CD) based nanoparticles (NPs) with a mean diameter of 340 (±7) nm, a ζ-potential value of +18.3 (±0.5) mV and coated with thiolated low molecular weight hyaluronic acid were formulated to improve both the solubility and the residential time in the conjunctival sac of the loaded drug IND. The NPs were prepared through the ionotropic gelation technique, exploiting the interaction between the positively charged amino group of CS and the negatively charged sulfonic group of SBE-β-CD. The mucoadhesive properties of the NPs were evaluated on chicken trachea and esophagus tissues using a texture analyser. The irritability effects of NPs were disclaimed with Hecam test. The developed coated NPs showed increased residential time in the conjunctival sac, displayed no irritancy or toxicity for local administration, making them an optimal and innovative drug delivery system for the treatment of anterior segment inflammation diseases. On the other hand, the uncoated NPs displayed better permeating properties since they are smaller and could be further exploited for the treatment of posterior segment diseases.
吲哚美辛（IND）是一种局部应用的药物，用于治疗前节疾病，如结膜炎、葡萄膜炎和白内障手术后的炎症预防，以及后节疾病如黄斑水肿。目前，IND 以 0.1% w/v 的羟丙基-β-环糊精为基础的滴眼剂制剂形式存在，其生物利用度受到多种因素的限制，如鼻泪管引流、反射性眨眼和结膜囊体积小。在这项研究中，壳聚糖（CS）/磺丁基醚-β-环糊精（SBE-β-CD）为基础的纳米粒子（NPs），平均直径为 340（±7）nm，ζ-电位值为+18.3（±0.5）mV，表面涂有巯基化低分子量透明质酸，用于提高载药 IND 的溶解度和在结膜囊中的滞留时间。NPs 是通过离子凝胶技术制备的，利用 CS 的正电荷氨基基团与 SBE-β-CD 的负电荷磺酸基团之间的相互作用。通过质构仪评估 NPs 的粘膜粘附性能。通过 Hecam 测试否认了 NPs 的刺激性作用。所开发的涂层 NPs 显示出在结膜囊中滞留时间的增加，显示出对局部给药没有刺激性或毒性，使它们成为治疗前节炎症疾病的最佳创新药物传递系统。另一方面，未涂层的 NPs 表现出更好的渗透性能，因为它们更小，可以进一步用于治疗后节疾病。
