PLGA nanoparticles for intravitreal peptide delivery: statistical optimization, characterization and toxicity evaluation.
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.
a Buchanan Ocular Therapeutics Unit (BOTU), Department of Ophthalmology, New Zealand National Eye Center, Faculty of Medical and Health Sciences , University of Auckland , Auckland , New Zealand.
Rohit
R
Bisht
a Buchanan Ocular Therapeutics Unit (BOTU), Department of Ophthalmology, New Zealand National Eye Center, Faculty of Medical and Health Sciences , University of Auckland , Auckland , New Zealand.
Ilva D
http://orcid.org/0000-0001-5997-5994
ID
Rupenthal
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D016503:Drug Delivery Systems / Q000009:adverse effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D058449:Intravitreal Injections; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018675:Toxicity Tests; D015027:Zebrafish / Q000196:embryology
D004337:Drug Carriers; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Box–Behnken Design; PLGA nanoparticles; drug delivery; ocular peptide delivery; zebrafish embryo toxicity