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Self-Implantable Core-Shell Microneedle Patch for Long-Acting Treatment of Keratitis via Programmed Drug Release
Xue Jiang1, Yinli Jin1, Yongnian Zeng1
1Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.
Abstract:
Bacteria-induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self-implantable core-shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH-responsive antimicrobial nanoparticles (NPs), Ag@ZIF-8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti-angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF-8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core-shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti-angiogenic and anti-inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.
Insights
A novel microneedle patch delivers antimicrobial nanoparticles and an anti-angiogenic drug for bacterial keratitis. This self-implantable patch offers improved treatment compared to traditional antibiotic eyedrops.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Nanotechnology
Background:
- Bacterial keratitis is a leading cause of corneal blindness.
- Current antibiotic eyedrops have low bioavailability and require frequent administration due to corneal barriers and tear film washout.
- Effective treatment strategies are needed to overcome these limitations.
Purpose of the Study:
- To develop a self-implantable core-shell microneedle (MN) patch for programmed drug release in bacterial keratitis treatment.
- To combine antimicrobial and anti-angiogenic therapies within a single delivery system.
- To evaluate the efficacy of the MN patch compared to conventional eyedrops.
Main Methods:
- Fabrication of a core-shell MN patch encapsulating pH-responsive Ag@ZIF-8 nanoparticles (NPs) in the core and rapamycin (Rapa) in the shell.
- Designed for rapid release of Ag@ZIF-8 NPs and sustained release of Rapa.
- In vivo evaluation in a rat model of bacterial keratitis.
Main Results:
- The core-shell MN patch demonstrated programmed release of both Ag@ZIF-8 NPs and Rapa.
- A single administration achieved significant antimicrobial activity.
- Superior anti-angiogenic and anti-inflammatory effects were observed compared to daily eyedrops.
Conclusions:
- The self-implantable core-shell MN patch offers a promising therapeutic strategy for bacterial keratitis.
- Programmed drug release enhances treatment efficacy and patient compliance.
- This approach holds potential for clinical application in infectious keratitis therapy.
