Related Experiment Video
Updated: Jun 30, 2026
Formulation of Diblock Polymeric Nanoparticles through Nanoprecipitation Technique
Published on: September 20, 2011
Thermosensitive Tri-Block Polymer Nanoparticle-Hydrogel Composites as Payloads of Natamycin for Antifungal Therapy
Xiaoyuan Sha1, Leung Chan1, Xiaoyi Fan2
1Department of Ophthalmology, The First Affiliated Hospital, and Department of Chemistry, Jinan University, Guangzhou, People's Republic of China.
Purpose:
Fusarium Solani is the principal pathogen associated with fungal keratitis. As a sensitive drug to F. Solani, natamycin (NAT) was limited by the poor penetration and low bioavailability in clinical application. The aim of this study was to develop a new type of tri-block polymer nanoparticle-gel complex (Gel@PLGA-PEI-PEG@NAT) for delivering NAT and evaluate its physicochemical properties, antifungal activity, safety, penetrability, adhesion, and efficacy in treating fungal keratitis.
Methods:
PLGA-PEI-PEG@NAT was prepared and characterized with a nano-particle size analyzer, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The minimum inhibitory concentration (MIC), cytotoxicity, penetrability of NAT (Natacyn® 5% ophthalmic suspension; Alcon) and PLGA-PEI-PEG@NAT with different concentrations were assessed. The eye surface retention time, ocular irritation, and curative effect of the NAT ophthalmic suspension and Gel@PLGA-PEI-PEG@NAT on a rabbit fungal keratitis model were evaluated.
Results:
PLGA-PEI-PEG@NAT had a particle size of 150 nm, a positive surface charge, and a sustained-release effect. The MIC for F. Solani was 2 μg/mL. A cytotoxicity test and ocular irritation test showed that PLGA-PEI-PEG@NAT and Gel@PLGA-PEI-PEG@NAT had good biocompatibility and no obvious irritation for rabbit corneas. Penetration experiments confirmed that PLGA-PEI-PEG@NAT can successfully enter corneal epithelial cells and through the cornea to enter the anterior chamber. Compared with NAT ophthalmic suspension, Gel@PLGA-PEI-PEG@NAT had stronger cornea permeation at the same concentration. The therapeutic effect and precorneal retention ability of the NAT ophthalmic suspension and Gel@PLGA-PEI-PEG@NAT on the fungal keratitis rabbit model were compared. Gel@PLGA-PEI-PEG@NAT achieved a better therapeutic effect at a lower drug concentration, and its eye surface retention time was significantly longer than that of the NAT ophthalmic suspension.
Conclusion:
Gel@PLGA-PEI-PEG@NAT was shown to be a safe and effective nanodrug delivery system for NAT. It has great potential to improve the cure rate of fungal keratitis, reduce the administration frequency during the treatment process, and improve patient compliance.
Insights
A novel nanoparticle-gel complex effectively delivers natamycin (NAT) for fungal keratitis treatment. This system enhances drug penetration and retention, offering a safer and more effective therapeutic option.
Area of Science:
- Ophthalmology
- Nanotechnology
- Mycology
Background:
- Fungal keratitis is primarily caused by Fusarium Solani.
- Natamycin (NAT) is effective against F. Solani but has poor ocular penetration and bioavailability.
- Existing treatments face challenges in clinical application due to drug delivery limitations.
Purpose of the Study:
- To develop a tri-block polymer nanoparticle-gel complex (Gel@PLGA-PEI-PEG@NAT) for improved natamycin (NAT) delivery.
- To evaluate the physicochemical properties, antifungal activity, safety, and efficacy of the novel NAT delivery system.
- To assess the system's penetrability, adhesion, and therapeutic potential in treating fungal keratitis.
Main Methods:
- Preparation and characterization of PLGA-PEI-PEG@NAT nanoparticles using techniques like TEM, SEM, and FTIR.
- Assessment of minimum inhibitory concentration (MIC), cytotoxicity, and ocular penetration of NAT and the nanoparticle formulation.
- Evaluation of therapeutic efficacy, ocular irritation, and eye surface retention time in a rabbit fungal keratitis model.
Main Results:
- The developed Gel@PLGA-PEI-PEG@NAT exhibited a particle size of 150 nm, positive surface charge, and sustained drug release.
- The formulation demonstrated good biocompatibility and minimal ocular irritation in rabbit corneas.
- Gel@PLGA-PEI-PEG@NAT showed enhanced corneal permeation and superior therapeutic effects with longer precorneal retention compared to conventional NAT suspension.
Conclusions:
- Gel@PLGA-PEI-PEG@NAT represents a safe and effective nanodrug delivery system for natamycin.
- This system holds significant potential for improving fungal keratitis cure rates and patient compliance.
- The enhanced delivery system may allow for reduced administration frequency and lower drug concentrations during treatment.
