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Purpose <p>To overcome the challenges of conventional ocular formulations, such as poor bioavailability and rapid clearance, this study aims to crosslink chitosan (CS) and gellan gum (GG) polymers to develop and optimize citicoline-loaded chitosan-gellan gum nanoparticles (CT-CS-GG<sub>NPs</sub>) for enhanced ocular drug delivery and controlled release, emphasizing glaucoma treatment by protecting neuronal function.</p> Methods <p>CT-CS-GG<sub>NPs</sub> were fabricated by crosslinking CS and GG via the ionic gelation method and were optimized using a central composite design with three levels and two factors to assess the influence of chitosan and gellan gum concentration on % entrapment efficiency&#xa0;(%EE), polydispersity index (PDI), zeta potential (ZP) and particle size (PS). The optimized formulation (CT-CS-GG<sub>NPsopt</sub>) was further examined by FTIR, TEM, DSC, drug release (In-Vitro) &amp; Ex-Vivo including HET CAM and permeation Studies etc.</p> Results <p>The mean values obtained from 13 batches of CT-CS-GG<sub>NPs</sub> for PS, %EE, PDI, and ZP varied within the range of 241.3 to 990.2&#xa0;nm, 12% to 83.33%, 0.302 to 0.978, and 1.23 to 35.2&#xa0;mV respectively. CT-CS-GG<sub>NPsopt</sub> demonstrated extended in-vitro drug release, reaching 70.6 ± 1.9% over 12&#xa0;h. Ex-vivo HET-CAM and permeation studies confirmed the non-irritant nature of CT-CS-GG<sub>NPsopt</sub> and demonstrated a 2.2-fold higher drug uptake by the goat cornea compared to the drug solution.</p> Conclusion <p>CS and GG were successfully crosslinked to prepare CT-CS-GG<sub>NPs</sub>, which exhibit prolonged drug release, potentially enhancing drug absorption and therapeutic effectiveness while showing promise as safe carriers for ocular drug delivery.</p>

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Crosslinked Chitosan-Gellan Gum Nanoparticles for Enhanced Ocular Delivery of Citicoline in Glaucoma Management: Fabrication, Optimization, and Characterization

  • 期刊论文

  • 发表日期：

    2025年6月14日

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  • Gurpreet Kandav,
  • Tamanna Sharma,
  • Akash Chandel

摘要

Purpose

To overcome the challenges of conventional ocular formulations, such as poor bioavailability and rapid clearance, this study aims to crosslink chitosan (CS) and gellan gum (GG) polymers to develop and optimize citicoline-loaded chitosan-gellan gum nanoparticles (CT-CS-GGNPs) for enhanced ocular drug delivery and controlled release, emphasizing glaucoma treatment by protecting neuronal function.

Methods

CT-CS-GGNPs were fabricated by crosslinking CS and GG via the ionic gelation method and were optimized using a central composite design with three levels and two factors to assess the influence of chitosan and gellan gum concentration on % entrapment efficiency (%EE), polydispersity index (PDI), zeta potential (ZP) and particle size (PS). The optimized formulation (CT-CS-GGNPsopt) was further examined by FTIR, TEM, DSC, drug release (In-Vitro) & Ex-Vivo including HET CAM and permeation Studies etc.

Results

The mean values obtained from 13 batches of CT-CS-GGNPs for PS, %EE, PDI, and ZP varied within the range of 241.3 to 990.2 nm, 12% to 83.33%, 0.302 to 0.978, and 1.23 to 35.2 mV respectively. CT-CS-GGNPsopt demonstrated extended in-vitro drug release, reaching 70.6 ± 1.9% over 12 h. Ex-vivo HET-CAM and permeation studies confirmed the non-irritant nature of CT-CS-GGNPsopt and demonstrated a 2.2-fold higher drug uptake by the goat cornea compared to the drug solution.

Conclusion

CS and GG were successfully crosslinked to prepare CT-CS-GGNPs, which exhibit prolonged drug release, potentially enhancing drug absorption and therapeutic effectiveness while showing promise as safe carriers for ocular drug delivery.