Characterization of Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Ranibizumab.

Content Provider	Europe PMC
Author	Liu, Wenqiang Borrell, Marta Arias Venerus, David C. Mieler, William F. Kang-Mieler, Jennifer J.
Copyright Year	2019
Abstract	PurposeTo characterize a biodegradable microsphere-hydrogel drug delivery system (DDS) for controlled and extended release of ranibizumab.MethodsThe degradable microsphere-hydrogel DDSs were fabricated by suspending ranibizumab-loaded or blank poly(lactic-co-glycolic acid) microspheres within a poly(ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) hydrogel. The thermal responsive behavior of various DDS formulations was characterized in terms of volume phase transition temperature (VPTT) and swelling ratios changes from 22°C to 42°C. The mechanical properties were characterized using rheological methods. Degradability of hydrogels were also examined via wet weight loss. Finally, Iodine-125 was used to radiolabel ranibizumab for characterization of encapsulation efficiency and in vitro release.ResultsAll DDS formulations investigated were injectable through a 28-gauge needle at room temperature. The VPTT increased with increase of cross-linker concentration. The swelling ratios decreased as temperature increased and were not influenced by presence of microspheres. Rheology data confirmed that increase of cross-linker concentration and microsphere loading made DDS stiffer. Increase of degradable cross-linker concentration facilitated hydrogel in vitro degradation. Controlled release of ranibizumab were achieved for investigated DDS formulations for 6 months; and increased degradable cross-linker concentration produced faster and more complete release.ConclusionsThe biodegradable DDSs are suitable for sustained release of ranibizumab. Considering ease of injection, degradability and release of ranibizumab, DDS with 3 mM cross-linker concentration and less than 20 mg/mL microsphere loadings is more favorable for future application.Translational RelevanceThe investigated DDS is promising for controlled and extended release of anti-VEGF therapeutics to achieve better treatment regimen in ocular neovascularizations.
Journal	Translational Vision Science & Technology
Volume Number	8
PubMed Central reference number	PMC6350854
Issue Number	1
PubMed reference number	30701127
e-ISSN	21642591
DOI	10.1167/tvst.8.1.12
Language	English
Publisher	The Association for Research in Vision and Ophthalmology
Publisher Date	2019-01-22
Access Restriction	Open
Rights License	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Copyright 2019 The Authors
Subject Keyword	ocular drug delivery anti-VEGF AMD
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering Ophthalmology