PLGA nanoparticles for intravitreal peptide delivery: statistical optimization, characterization and toxicity evaluation

Abstract

Frequent intravitreal injections are currently used to overcome the ocular barriers and provide sufficient drug to the posterior eye segment. However, intravitreal injections have been associated with a number of complications and high treatment costs. To overcome these limitations, peptide-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) were developed using the nanoprecipitation technique and were optimized via Box–Behnken Design (BBD) and Response Surface Methodology (RSM). Developed NPs were evaluated for potential toxicity and cell apoptosis using the zebrafish embryo toxicity (ZET) model with titanium dioxide NPs and ethanol (1% v/v) serving as positive controls. Developed NPs had a size of 75.6–153.8 nm, a polydispersity index between 0.11 and 0.25 and a zeta potential of −9.4 to −46.0 mV. Loaded peptide was found to be stable under various experimental conditions tested. BBD and RSM were validated through the characterization of optimized formulations. Survival and hatching rates of NP-treated zebrafish 0–144 h post-fertilization were found to be normal with no significant malformations. Cellular apoptosis studies also endorsed the non-cytotoxic nature of the NPs. The overall results indicate that optimized PLGA nanoparticles could be a promising platform for efficient peptide delivery to the posterior segment of the eye.

Keywords:

• Box–Behnken Design
• drug delivery
• ocular peptide delivery
• PLGA nanoparticles
• zebrafish embryo toxicity

Acknowledgements

The authors would like to thank the Zebrafish Facility as well as the Auckland Cancer Society Research Center for providing research facilities and expertise related to these studies. The authors thank Verity F. Oliver, Department of Ophthalmology, for her help with ZET studies and Sreevalsan Sreebhavan, Auckland Cancer Society Research Center, for his technical support during HPLC analysis.

Disclosure statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.