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Amphotericin B containing microneedle ocular patch for effective treatment of fungal keratitis
Girdhari Roy1, Rohini Devi Galigama1, Veda Suresh Thorat1
1Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India.
Abstract:
Topical application of poorly water-soluble antibiotics cannot achieve the desired therapeutic concentration within cornea. The purpose of this study was to fabricate, characterize and evaluate in-vivo effectiveness of amphotericin B (AmB) containing microneedle ocular patch (MOP) against fungal keratitis. MOP containing free or liposomal AmB was fabricated using micromolding technique to mimic contact lens. MOPs were prepared using dissolvable polymeric matrix including polyvinyl alcohol and polyvinyl pyrrolidone. AmB loaded MOP were studied for their physical and mechanical properties, drug loading and dissolution rate, corneal insertion and drug permeability. MOP loaded with 100 µg AmB had a compression strength of 35.1 ± 6.7 N and required an insertional force of 1.07 ± 0.17 N in excised human cornea. Ex-vivo corneal permeation studies revealed significant enhancement in AmB corneal retention with the application of MOP compared with free AmB or liposomal AmB application. Furthermore, AmB loaded MOP application significantly (P < 0.05) reduced the Candida albicans load within cornea as evaluated in both ex-vivo model and in-vivo rabbit infection model. Histological examination showed that AmB MOP treatment improved the epithelial and stromal differentiation of corneal membrane. AmB containing MOPs can be developed as minimally invasive corneal delivery device for effective treatment of fungal keratitis.
Insights
This study developed a novel microneedle ocular patch (MOP) for delivering amphotericin B (AmB) to treat fungal keratitis. The AmB-loaded MOP demonstrated enhanced corneal drug delivery and effectively reduced Candida albicans load in preclinical models.
Area of Science:
- Ophthalmology
- Pharmaceutics
- Biomaterials Science
Background:
- Topical antibiotic delivery to the cornea is limited by poor water solubility and low therapeutic concentrations.
- Fungal keratitis requires effective drug delivery systems for improved treatment outcomes.
Purpose of the Study:
- To fabricate and characterize amphotericin B (AmB) microneedle ocular patches (MOPs).
- To evaluate the in-vivo efficacy of AmB-loaded MOPs against fungal keratitis.
Main Methods:
- Micromolding technique used to create dissolvable polymeric MOPs (polyvinyl alcohol, polyvinyl pyrrolidone) loaded with AmB.
- Assessment of physical, mechanical, drug loading, dissolution, corneal insertion, and permeability properties.
- In-vivo and ex-vivo models using rabbits and excised human corneas to evaluate efficacy against Candida albicans.
Main Results:
- AmB-loaded MOPs exhibited suitable mechanical strength for corneal insertion.
- Ex-vivo studies showed enhanced corneal retention and permeation of AmB with MOPs compared to free or liposomal AmB.
- Significant reduction in Candida albicans corneal load and improved corneal tissue differentiation observed in AmB MOP treated models.
Conclusions:
- AmB-loaded MOPs represent a promising, minimally invasive drug delivery system for fungal keratitis.
- The MOP technology enhances corneal drug concentration and therapeutic effectiveness.
- Further development of AmB-containing MOPs could offer a superior treatment option for fungal eye infections.
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