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Solid Dispersion Incorporated into Dissolving Microneedles for Improved Antifungal Activity of Amphotericin B: In
Muhammad Alif Sya'ban Mahfud1, Nor Atikah Syahirah1, Muhammad Akram1
1Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
Abstract:
Fungal keratitis (FK) is a fungal infection of the cornea, which is part of the eye and causes corneal ulcers and an increased risk of permanent blindness, which is often found in Candida albicans species. Amphotericin B (AMB), which is a group of polyenes as the first-line treatment of FK, is effective in annihilating C. albicans. However, AMB preparations such as eye drops and ointments have major drawbacks, for instance, requiring more frequent administrations, loss of the drug by the drainage process, and rapid elimination in the precornea, which result in low bioavailability of the drug. An ocular dissolving microneedle containing the solid dispersion amphotericin B (DMN-SD-AMB) had been developed using a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers, while the solid dispersion AMB (SD-AMB) was contained in the needle as a drug. This study aims to determine the most optimal and safest DMN-SD-AMB formula for the treatment of FK in the eye as well as a solution to overcome the low bioavailability of AMB eye drops and ointment preparations. SD-AMB had been successfully developed, which was characterized by increased antifungal activity and drug release in vitro compared to other treatments. Furthermore, DMN-SD-AMB studies had also been successfully performed with the best formulation, which exhibited the best ex vivo corneal permeation profile and antifungal activity as well as being safe from eye irritation. In addition, an in vivo antifungal activity using a rabbit infection model shows that the number of fungal colonies was 0.98 ± 0.11 log10 CFU/mL (F3), 5.76 ± 0.32 log10 CFU/mL (AMB eye drops), 4.01 ± 0.28 log10 CFU/mL (AMB ointments), and 9.09 ± 0.65 log10 CFU/mL (control), which differed significantly (p < 0.05). All of these results evidence that DMN-SD-AMB is a new approach to developing intraocular preparations for the treatment of FK.
Insights
A novel dissolving microneedle formulation of amphotericin B (AMB) significantly improved ocular drug delivery for fungal keratitis (FK). This innovation enhances AMB
Area of Science:
- Ophthalmology
- Mycology
- Pharmaceutics
Background:
- Fungal keratitis (FK) is a serious eye infection, often caused by Candida albicans, leading to corneal ulcers and potential blindness.
- Current first-line treatment, amphotericin B (AMB), suffers from low ocular bioavailability due to frequent administration needs and rapid elimination.
- Existing AMB eye drops and ointments have limitations, including poor drug retention and systemic drainage, necessitating improved delivery systems.
Purpose of the Study:
- To develop and optimize an ocular dissolving microneedle formulation containing solid dispersion amphotericin B (DMN-SD-AMB) for treating fungal keratitis.
- To enhance the bioavailability and efficacy of AMB in treating ocular fungal infections.
- To evaluate the safety and effectiveness of the DMN-SD-AMB formulation compared to conventional AMB preparations.
Main Methods:
- Development of solid dispersion amphotericin B (SD-AMB) and its incorporation into dissolving microneedles (DMNs) using PVA and PVP polymers.
- In vitro characterization of SD-AMB for antifungal activity and drug release kinetics.
- Ex vivo corneal permeation studies and in vivo efficacy assessment in a rabbit FK model.
Main Results:
- SD-AMB demonstrated enhanced antifungal activity and improved in vitro drug release compared to standard treatments.
- The optimal DMN-SD-AMB formulation showed superior ex vivo corneal permeation and significant in vivo antifungal activity.
- In vivo studies in rabbits revealed a substantial reduction in fungal colonies with DMN-SD-AMB (0.98 log10 CFU/mL) compared to AMB eye drops (5.76 log10 CFU/mL) and ointments (4.01 log10 CFU/mL).
Conclusions:
- DMN-SD-AMB represents a promising new approach for intraocular drug delivery, effectively overcoming the limitations of conventional AMB formulations for fungal keratitis.
- The developed microneedle system offers improved bioavailability, enhanced efficacy, and a safer alternative for treating ocular fungal infections.
- This innovative formulation holds potential for reducing the risk of blindness associated with fungal keratitis through more effective AMB delivery.
