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Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections
Alyaa A Albadr1,2, Ismaiel A Tekko1,3, Lalitkumar K Vora1
1School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
Abstract:
Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)-based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays' reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch.
Insights
Biodegradable microneedles effectively deliver amphotericin B (AMP-B) for fungal eye infections. This approach enhances drug penetration and preserves antifungal activity while reducing toxicity, offering a promising treatment for ocular fungal infections.
Area of Science:
- Ophthalmology
- Pharmaceutics
- Biomaterials Science
Background:
- Ocular fungal infections pose a significant risk of blindness if untreated.
- Topical amphotericin B (AMP-B) is a primary treatment, but its poor solubility and corneal penetration limit bioavailability.
- Microneedles (MNs) offer a minimally invasive strategy to improve ocular drug delivery.
Purpose of the Study:
- To investigate the use of rapidly dissolving, biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)-based microneedles for ocular delivery of amphotericin B (AMP-B).
- To evaluate the potential of these microneedles to enhance AMP-B permeation and efficacy in treating fungal keratitis.
Main Methods:
- Fabrication of biodegradable PVP/HA microneedle arrays for AMP-B delivery.
- Assessment of microneedle array reproducibility, mechanical strength, and dissolution properties.
- Evaluation of corneal penetration and drug permeation using multiphoton microscopy.
- In vitro assessment of AMP-B cytotoxicity and antifungal activity of microneedle formulations.
Main Results:
- PVP/HA microneedle arrays demonstrated good reproducibility, mechanical strength, and rapid dissolution with complete drug recovery.
- Microneedles successfully penetrated corneal tissue, significantly enhancing AMP-B permeation.
- PVP/HA formulations reduced AMP-B cytotoxicity compared to the free drug.
- The microneedle-delivered AMP-B retained its antifungal activity, effectively inhibiting fungal growth.
Conclusions:
- Biodegradable PVP/HA microneedle patches provide a feasible and effective method for ocular delivery of poorly soluble amphotericin B.
- This microneedle-based approach enhances corneal drug penetration and maintains therapeutic efficacy while improving safety profiles.
- Microneedle technology presents a promising strategy for improving the treatment of fungal keratitis.
