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<p>Fungal keratitis (FK) is a severe ocular disease that may cause blindness in severe cases. The only FDA-approved first-line treatment drug is natamycin (NAT). However, NAT bioavailability is less than 2% due to special environment of the eye. To address this issue, hydroxypropyl-β-cyclodextrin (HPCD) was applied in this study to form a hydrophilic coating on the surface of nanoparticles. The FTIR analysis suggested interactions between HPCD and the nanoparticle components, which may contribute to the enhanced colloidal stability. As a result, the nanoparticles with a hydrophilic membrane (F2) demonstrated more superior stability than the plain nanoparticle (F1). Furthermore, compared to the NAT suspension, surface wetting of F2 enhanced significantly, the cumulative drug release reduced by 27.34% at 72&#xa0;h, isolated corneal permeability increased 2.89-fold, as well as protein binding was upgraded 6.1-fold at 30&#xa0;s. Subsequently, F2 was incorporated into a temperature- and osmolarity dual-responsive ophthalmic gel (Tem-Osm gel). The Tem-Osm gel behaved a shear-thinning non-Newtonian fluid, which exhibited excellent biocompatibility and higher ocular bioavailability. Moreover, the in vitro antifungal experiments demonstrated that F2 and Tem-Osm gel exhibited more superior antifungal activity, lower MIC/EC50 values and larger inhibition zones than the NAT suspension. Overall, the study indicates that the novel combination of nanoparticle and multi-responsive ocular gel sustained-release delivery system holds promising potential as a therapeutic approach for fungal keratitis.</p>

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Temperature and osmotic pressure dual-stimuli-responsive ophthalmic gels embedded with HPCD-modified nanoparticles for prolonged-release delivery of natamycin

  • 期刊论文

  • 发表日期：

    2026年7月23日

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  • Bixia Lin,
  • Fangfei Fan,
  • Hui Xu,
  • Xin Li,
  • Yufei Li,
  • Chunya Qin,
  • Xiaoyun Zhang,
  • Shiqiang Zhang,
  • Yang Gao,
  • Lirong Niu

摘要

Fungal keratitis (FK) is a severe ocular disease that may cause blindness in severe cases. The only FDA-approved first-line treatment drug is natamycin (NAT). However, NAT bioavailability is less than 2% due to special environment of the eye. To address this issue, hydroxypropyl-β-cyclodextrin (HPCD) was applied in this study to form a hydrophilic coating on the surface of nanoparticles. The FTIR analysis suggested interactions between HPCD and the nanoparticle components, which may contribute to the enhanced colloidal stability. As a result, the nanoparticles with a hydrophilic membrane (F2) demonstrated more superior stability than the plain nanoparticle (F1). Furthermore, compared to the NAT suspension, surface wetting of F2 enhanced significantly, the cumulative drug release reduced by 27.34% at 72 h, isolated corneal permeability increased 2.89-fold, as well as protein binding was upgraded 6.1-fold at 30 s. Subsequently, F2 was incorporated into a temperature- and osmolarity dual-responsive ophthalmic gel (Tem-Osm gel). The Tem-Osm gel behaved a shear-thinning non-Newtonian fluid, which exhibited excellent biocompatibility and higher ocular bioavailability. Moreover, the in vitro antifungal experiments demonstrated that F2 and Tem-Osm gel exhibited more superior antifungal activity, lower MIC/EC50 values and larger inhibition zones than the NAT suspension. Overall, the study indicates that the novel combination of nanoparticle and multi-responsive ocular gel sustained-release delivery system holds promising potential as a therapeutic approach for fungal keratitis.