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In-situ forming PLGA implants for intraocular dexamethasone delivery
C Bode1, H Kranz2, F Siepmann1
1Univ. Lille, Inserm, CHU Lille, U1008, 59000 Lille, France.
International Journal of Pharmaceutics
|July 8, 2018
Summary
Researchers developed in-situ forming implants using poly(lactic-co-glycolic acid) (PLGA) for controlled dexamethasone ocular delivery. Implant properties and drug release kinetics were optimized by controlling formulation factors and understanding degradation mechanisms.
Area of Science:
- Biomaterials Science
- Ophthalmology
- Drug Delivery Systems
Background:
- Ocular drug delivery faces challenges due to rapid clearance and limited bioavailability.
- In-situ forming implants offer sustained drug release for improved ocular therapy.
- Poly(lactic-co-glycolic acid) (PLGA) is a versatile biodegradable polymer for controlled release applications.
Purpose of the Study:
- To develop and characterize in-situ forming implants for controlled ocular delivery of dexamethasone.
- To investigate the influence of formulation parameters on dexamethasone release kinetics.
- To understand the physico-chemical changes governing implant degradation and drug release.
Main Methods:
- Preparation of PLGA-based in-situ forming implants with dexamethasone.
- Physico-chemical characterization including mass change, morphology, molecular weight, pH, and solvent content.
- In-vitro drug release studies in phosphate buffer (pH 7.4).
- Analysis of factors affecting drug release: release medium volume, drug content, polymer molecular weight, and PLGA concentration.
Main Results:
- Implant properties and drug release kinetics were significantly influenced by polymer molecular weight and PLGA concentration.
- The systems demonstrated robustness against variations in vitreous humor volume.
- Limited drug solubility in the implant and medium played a key role in controlling release at 7.5% drug loading.
- Polymer precipitation during solvent exchange and subsequent swelling behavior dictated internal structure and mass transport.
Conclusions:
- PLGA-based in-situ forming implants provide a viable strategy for controlled ocular dexamethasone delivery.
- Formulation parameters critically control implant structure, degradation, and drug release profiles.
- Understanding solubility effects and polymer precipitation is crucial for optimizing ocular drug delivery systems.
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