Preparation and evaluation of PLGA nanoparticle-loaded biodegradable light-responsive injectable implants as a promising platform for intravitreal drug delivery

The present study reports on the development of a hybrid system by integrating poly(lactic-co-glycolic)acid nanoparticles (PLGA NPs) into light-responsive in-situ forming injectable implants (ISFIs) for minimally invasive and safe intravitreal peptide delivery. In the first part of the study, peptide-loaded PLGA based nanoparticles (NPs) were developed using the two-step nanoprecipitation technique. Peptide compatibility with PLGA and polyvinyl alcohol was confirmed via IR spectroscopy. Developed NPs had a size of 149.3-235.4 nm, a polydispersity index between 0.24 and 0.46, a zeta potential of −32.4 to −27.0 mV and an entrapment efficiency of 34.3-55.3%. In the second part of the study, successful synthesis of methacrylated alginate (MA) and its subsequent photocrosslinking upon photoirridiation was confirmed by 1H NMR. Photocrosslinked MA exhibited the required clarity and its gelling time, morphology, syringeability, hardness, rate of swelling and degradation were found suitable for prolonging its residence in the posterior segment. The sulforhodamine B assay on human retinal pigment epithelium cells and the zebrafish embryo toxicity test confirmed the biocompatibility of NPs and ISFIs. Finally, NPs were incorporated into the ISFIs for improved particle retention and to further sustain drug release, suggesting the proposed hybrid system as an innovative and efficient ocular drug delivery platform.

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