Drug Delivery Nanoparticles: Toxicity Comparison in Retinal Pigment Epithelium and Retinal Vascular Endothelial Cells

Abstract

Multiple synthetic polymer nanoparticles (NPs) have been widely used as drug delivery systems. However, their toxicity to the retinal pigment epithelium and retinal endothelium remains unclear. In this study, we analyze the cytotoxic effects of three different kinds of NPs, made of poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and PEGylated PLGA (PEG-PLGA), in a retinal pigment epithelium cell line (ARPE-19) and in primary human retinal vascular endothelial cells (RVEC). PEG-PLGA NPs presented the lowest cytotoxicity on ARPE-19 cells and RVEC as assessed by MTT viability assay. While PLGA and PCL exhibited variable amount of toxicity, no significant toxicity was observed when incubating cells with high PEG-PLGA concentrations (100ug/ml), for up to 6 days. On both transmission electron microscopy and confocal microscopy, Rhodamine 6G-loaded PEG-PLGA NPs were observed intracellularly in multiple subcellular organelles. PEG-PLGA NPs are a potentially viable option for the treatment of eye diseases.

Development and In Vitro Evaluation of 2-Methoxyestradiol Loaded Polymeric Micelles for Enhancing Anticancer Activities in Prostate Cancer

“…These high concentrations of formulation excipients might have contributed to the slight decrease in the cell viability at higher studied concentrations. The concentration-dependent increase in cytotoxicity of PEG-PLGA polymer has been demonstrated in previous studies, even at concentrations below 200 µg/mL [ 36 ]. Further, it has been demonstrated that even the shape of nanoparticles formed with PEG-PLGA polymer influences their cytotoxicity, and shows cytotoxicity even below a concentration of 100 µg/mL [ 37 ].…”

Effects of gold and PCL- or PLLA-coated silica nanoparticles on brain endothelial cells and the blood–brain barrier

“…Hence, variations in surface characteristics, composition and size of the NPs and the various cell types used are likely to account for differences between the studies. This is corroborated by comparisons of the effects of different types of NPs on the cell viability of different cell types [28,32].…”

“…PEG- b -PCL-NPs were highly biocompatible and did not cause significant cell viability reductions when added to hCMEC/D3 cells at concentrations of [0.01–1 mg/mL] [27]. PCL-NPs resulted in different cytotoxicity in human retinal vascular ECs, exhibiting stronger effects in the latter at concentrations of [25 µg/mL] to [200 µg/mL] with up to 50% reduction in cell viability [28], indicating that different cell types react differently to similar NPs. In line with our findings, 20 nm PEGylated Au-NPs did affect the proliferation of HUVECs up to concentrations of [100 µg/mL], a lower Au-NP concentration than the one used in our study ([160.3 µg/mL]) [24].…”

Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration

“…Nevertheless, to avoid any hazards associated with systemic exposure, local application of CN03 to the eye is also a viable option. Besides the delivery as liposomal formulation it may be possible to combine CN03 with alternative drug delivery systems, such as poly(lactic- co -glycolic acid) for intraocular slow release ( 52 ) or cyclodextrins for topical delivery ( 53 ). Furthermore, the marked prolongation of its in vivo half-life with liposomal encapsulation, and the lack of therapeutic effect without, are in line with previous observations ( 19 , 39 ) and our findings thus stress the importance of efficient drug delivery for the treatment of retinal diseases.…”