Abstract：
The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ - LP) using a simple one-step fabrication approach followed byoptimization employing a 32 Full Factorial Design. The ACZ - LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ - LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ - LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.
摘要：
眼睛的复杂结构对有效输送药物提出了挑战，这可以通过使用纳米技术来规避。本研究旨在使用简单的一步制造方法制备乙酰唑胺-loadedleciplex（ACZ-LP），然后采用32全因子设计进行优化。ACZ-LP具有很高的包封效率（93.25±2.32％），记录的平均直径约为171.03±3.32，单分散尺寸分布和zeta电位为41.33±2.10mV。制备的制剂的体外释放和离体渗透研究表明，与普通的乙酰唑胺溶液相比，在1小时内开始突释，然后是持续释放模式。此外，离体角膜药物保留（27.05±1.20％）和使用不同浓度粘蛋白的体外粘膜粘附研究表明，强静电结合证实了制剂的粘膜粘附特性。此外,组织病理学研究确保了制剂无刺激性和无毒,而HET-CAM确保了制剂的基本耐受性.在兔模型上进行的体内药效学研究表明，与普通乙酰唑胺溶液相比，用ACZ-LP治疗导致眼内压显著和延长的降低。乙酰唑胺口服片，和Brinzox®。总之,ACZ-LP是一种有效且通用的药物递送方法,在控制青光眼方面显示出显著的潜力.
