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Published on: September 27, 2021
Naturally derived mucoadhesive nanosuspension for treatment of multiple staged ocular infections
Yuting Zheng1, Liangju Kuang2, Cathy Lu1
1Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095, United States.
Abstract:
Bacterial ocular infections pose significant risks to vision and incur substantial economic burdens worldwide. Current standards of care, such as eye drops and ointments, suffer from poor drug bioavailability (<5 %), rapid clearance, and insufficient retention, preventing dual prophylactic and therapeutic efficacy. To address these limitations, we developed naturally derived mucoadhesive gelatin methacryloyl (GelMA) nanoparticles (NPs) functionalized with phenylboronic acid (PBA), named GelMAP, for the sustained delivery of moxifloxacin (MFX), a broad-spectrum antibacterial agent. Dispersed in a custom-designed shear-thinning matrix formulated with hyaluronic acid (HA) to enhance viscosity and ocular retention, the GelMAP nanosuspension exhibited robust mucoadhesion, efficient drug loading (>70 %), and sustained in vitro drug release. Biocompatibility and bactericidal efficacy were confirmed in vitro, showing >95 % cell viability in NIH 3T3 and human corneal epithelial cells, along with notable antibacterial activity against key ocular pathogens over 7 days. In a healthy murine model, the biosafety of the nanosuspension was confirmed. The MFX-loaded nanosuspension demonstrated around 2.6-fold longer half-life in the cornea compared to commercial MFX drops (Vigamox®), indicating higher drug retention. Designed to prevent infection and treat established conditions, its efficacy was evaluated in a murine bacterial keratitis model. The MFX-loaded nanosuspension outperformed Vigamox® by reducing corneal opacity, achieving lower clinical scores (indicating better outcomes), and decreasing bacterial counts. Histological analysis showed minimal inflammation and a preserved corneal structure, validating the effectiveness of the GelMAP nanosuspension. Currently, no NP formulation has been widely demonstrated to offer dual efficacy in both early and established infections, underscoring GelMAP nanosuspension's potential for comprehensive ocular infection management by reducing treatment frequency, minimizing complications, and enhancing patient compliance.
Insights
New gelatin methacryloyl (GelMA) nanoparticles (NPs) offer sustained delivery of moxifloxacin (MFX) for bacterial eye infections. This novel nanosuspension improves drug retention and efficacy, potentially enhancing treatment for ocular infections.
Area of Science:
- Biomaterials Science
- Ophthalmology
- Nanotechnology
Background:
- Bacterial ocular infections cause significant vision loss and economic impact.
- Current treatments like eye drops have poor bioavailability (<5%), rapid clearance, and insufficient retention.
- Existing therapies lack dual prophylactic and therapeutic efficacy for ocular infections.
Purpose of the Study:
- To develop a novel nanoparticle (NP) formulation for sustained antibacterial drug delivery to the eye.
- To enhance ocular drug retention and bioavailability for improved treatment of bacterial keratitis.
- To create a formulation with dual efficacy for both preventing and treating ocular infections.
Main Methods:
- Developed mucoadhesive gelatin methacryloyl (GelMA) nanoparticles (NPs) functionalized with phenylboronic acid (PBA), named GelMAP.
- Formulated GelMAP with moxifloxacin (MFX) in a hyaluronic acid (HA) based shear-thinning matrix.
- Evaluated in vitro mucoadhesion, drug loading, release kinetics, biocompatibility, and antibacterial activity.
- Assessed in vivo biosafety, corneal drug retention (half-life), and therapeutic efficacy in a murine bacterial keratitis model.
Main Results:
- GelMAP nanosuspension showed robust mucoadhesion, high drug loading (>70%), and sustained in vitro drug release.
- Demonstrated excellent in vitro biocompatibility (>95% cell viability) and sustained bactericidal activity over 7 days.
- Achieved a 2.6-fold longer corneal half-life compared to commercial moxifloxacin drops (Vigamox®).
- In vivo, MFX-loaded GelMAP significantly reduced corneal opacity, clinical scores, and bacterial load in a keratitis model.
- Histological analysis revealed minimal inflammation and preserved corneal structure post-treatment.
Conclusions:
- The developed GelMAP nanosuspension provides effective, sustained delivery of moxifloxacin for bacterial ocular infections.
- This formulation significantly enhances ocular drug retention and demonstrates superior therapeutic efficacy compared to conventional eye drops.
- GelMAP nanosuspension holds promise for comprehensive ocular infection management, offering dual prophylactic and therapeutic benefits with improved patient compliance.
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