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Intravitreal long-term sustained ranibizumab delivery using injectable microgel-embedded hydrogel.
Simin Lee1, Jun Young Park2,3, Hye Kyoung Hong2
1Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.
Asian Journal of Pharmaceutical Sciences
|October 30, 2024
Summary
This study developed an injectable hydrogel for sustained delivery of ranibizumab (RBZ) to treat retinal vascular disease. The new formulation reduces injection frequency and improves drug retention in the eye.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Drug Delivery Systems
Background:
- Retinal vascular diseases are a primary cause of vision loss.
- Current intravitreal treatments require frequent injections, leading to patient burden and complications.
- There is a need for sustained drug delivery systems for posterior segment eye diseases.
Purpose of the Study:
- To develop an injectable, biodegradable hyaluronan microgel-embedded gelatin-poly(ethylene glycol)-tyramine hydrogel (HmGh) for sustained intravitreal ranibizumab (RBZ) delivery.
- To reduce patient burden and minimize side effects associated with frequent intravitreal injections.
- To evaluate the drug release kinetics, efficacy, and safety of the HmGh system.
Main Methods:
- Fabrication and characterization of the hyaluronan microgel (Hm)-embedded gelatin-poly(ethylene glycol)-tyramine hydrogel (HmGh).
- In vitro assessment of RBZ loading, release profiles, cytocompatibility, and cellular drug efficacy.
- In vivo evaluation in an animal model to determine RBZ concentrations in vitreous and retina over time.
- Pharmacokinetic analysis comparing HmGh to RBZ-loaded Hm and RBZ solution.
- Intraocular safety and degradation assessment using fundus imaging and histological analysis.
Main Results:
- HmGh demonstrated controlled RBZ loading and release, minimizing initial burst release.
- In vivo studies showed sustained RBZ concentrations in the vitreous and retina for over 120 days.
- Pharmacokinetic analysis revealed significantly longer half-lives for RBZ-loaded HmGh compared to RBZ-loaded Hm and RBZ solution.
- Reduced RBZ elimination into the aqueous humor from HmGh compared to other formulations.
- Intraocular safety and degradation were confirmed through fundus imaging and histology.
Conclusions:
- The injectable microgel-embedded hydrogel (HmGh) is a promising formulation for sustained intravitreal drug delivery.
- This system effectively reduces injection frequency and maintains therapeutic drug concentrations for posterior segment eye diseases.
- HmGh offers a safer and more convenient alternative for managing retinal vascular diseases and other ocular conditions.
