Scholarlink

<p>Glaucoma is a progressive eye disease characterized by persistently high intraocular pressure (IOP) and optic nerve damage, often resulting in irreversible vision loss. While Acetazolamide (ACZ) is a potent treatment, its clinical utility is severely limited by poor solubility and permeability (BCS Class IV), alongside systemic side effects from oral administration. This study aimed to develop an innovative ACZ-loaded nanoemulsion-based <i>in situ</i> gel (NE-InG) to enhance transcorneal delivery and provide sustained therapeutic action. The NE-InG was prepared via nanoprecipitation, utilizing poly-δ-decalactone (PDL) as the oil phase and Pluronic F68/HPMC as thermo-responsive gelling agents. Systematic optimization using a Box-Behnken Design (BBD) identified NE-InG 16 as the optimal formulation. This formulation exhibited superior physicochemical characteristics, including a droplet size of 246.4 nm, a polydispersity index of 0.120, and a zeta potential of -29.7 mV. The system demonstrated rapid gelation kinetics at ocular-surface temperatures, ensuring prolonged retention. <i>In vitro</i> studies showed sustained ACZ release over 24 h, following a non-Fickian transport mechanism. Furthermore, <i>ex vivo</i> studies confirmed significantly enhanced corneal permeability. <i>In vivo</i> rabbit models validated the formulation's safety via the Draize test and demonstrated a prolonged reduction in IOP for up to 22 h. Pharmacokinetic analysis revealed a superior C<sub>max</sub> and AUC compared to marketed formulations. Ultimately, this ACZ-loaded NE-InG successfully addresses the solubility and permeability challenges of the drug, offering a safe and effective platform to improve patient compliance and therapeutic outcomes in glaucoma management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Novel Thermosensitive Acetazolamide - Poly-δ-Decalactone (PDL) In Situ Gel for Enhanced Ocular Retention and Bioavailability for Effective Glaucoma Management

  • 期刊论文

  • 发表日期：

    2026年2月16日

查看全文
  • Ankita Kishore,
  • Prem Prakash Singh,
  • Rishikesh Gupta,
  • Peeyush Bhardwaj,
  • Brajesh Lodhi,
  • Priyanka Rathore,
  • Kuldeep Bansal,
  • Alok Kumar Mahor

摘要

Glaucoma is a progressive eye disease characterized by persistently high intraocular pressure (IOP) and optic nerve damage, often resulting in irreversible vision loss. While Acetazolamide (ACZ) is a potent treatment, its clinical utility is severely limited by poor solubility and permeability (BCS Class IV), alongside systemic side effects from oral administration. This study aimed to develop an innovative ACZ-loaded nanoemulsion-based in situ gel (NE-InG) to enhance transcorneal delivery and provide sustained therapeutic action. The NE-InG was prepared via nanoprecipitation, utilizing poly-δ-decalactone (PDL) as the oil phase and Pluronic F68/HPMC as thermo-responsive gelling agents. Systematic optimization using a Box-Behnken Design (BBD) identified NE-InG 16 as the optimal formulation. This formulation exhibited superior physicochemical characteristics, including a droplet size of 246.4 nm, a polydispersity index of 0.120, and a zeta potential of -29.7 mV. The system demonstrated rapid gelation kinetics at ocular-surface temperatures, ensuring prolonged retention. In vitro studies showed sustained ACZ release over 24 h, following a non-Fickian transport mechanism. Furthermore, ex vivo studies confirmed significantly enhanced corneal permeability. In vivo rabbit models validated the formulation's safety via the Draize test and demonstrated a prolonged reduction in IOP for up to 22 h. Pharmacokinetic analysis revealed a superior Cmax and AUC compared to marketed formulations. Ultimately, this ACZ-loaded NE-InG successfully addresses the solubility and permeability challenges of the drug, offering a safe and effective platform to improve patient compliance and therapeutic outcomes in glaucoma management.