Biodegradable Nanoparticles Based on Pseudo-Proteins Show Promise as Carriers for Ophthalmic Drug Delivery

Abstract

Purpose: Drug delivery to treat ocular diseases still is a challenge in ophthalmology. One way to achieve drug delivery that is investigated currently is topical administration of drug-loaded polymeric nanoparticles (NPs) that are able to penetrate ocular barriers. The purpose of this study was optimal preparation of NPs made from pseudo-proteins and evaluation of their ability to penetrate ocular tissues. Methods: Biodegradable NPs of various types were prepared by nanoprecipitation of pseudo-protein composed of l-leucine (L), 1,6-hexanediol (6), and sebacic acid (8) (8L6). Arginine-based cationic polyester amides 8R6 and comb-like polyester amide containing lateral PEG-2000 chains along with 8L6 anchoring fragments in the backbones were used to construct positively charged and PEGylated NPs. They were loaded with fluorescein diacetate (FDA) or rhodamine 6G (Rh6G) as fluorescent probes. Suspensions of the NPs were given to cultivated microglial cells and retinal pigment epithelial (RPE) cells as well as topically on eyes of C57BL/6 mice. Penetration of NPs into the eyes was checked by fluorescence analysis. Results: NPs were prepared, and their properties were characterized. Cultured microglial cells and RPE cells took up the NPs. After topical administration, penetration of NPs into the cornea of the eyes was clearly seen. Small amounts of fluorescent dyes were also found in the lens, the retina, and the sclera depending on the type of NPs. Conclusions: The results showed that the new NPs penetrate ocular tissues after topical administration and are internalized by the cells. This raises confidence that the NPs may be useful carriers of therapeutic agents for ocular delivery.

Fluorescent Nanosystems for Drug Tracking and Theranostics: Recent Applications in the Ocular Field

“…Corneal fluorescence was obtained as expected, while surprising results were the reaching of tissues such as the sclera and retina. Thus, they proved to be a promising delivery system for topical use in chronic eye diseases [ 139 ].…”

“…Moreover, rapid clearance remains a challenge for nanosystems as they need to release their payload before being eliminated from the eye. Many studies focus on assessing the distribution in various tissues once the formulation has been instilled into the eye [ 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 134 , 137 , 138 , 139 ]. Unfortunately, few studies focus on assessing how mechanisms including blinking, tear drainage and ocular metabolism may interact with nanosystems [ 66 , 115 ].…”

Dexamethasone-Loaded Pseudo-Protein Nanoparticles for Ocular Drug Delivery: Evaluation of Drug Encapsulation Efficiency and Drug Release

“…Furthermore, in this work, we showed that the pseudo-protein 8L6 was the best in terms of particle size, stability, and cell compatibility. In another work [21], we prepared fuorescently tagged 8L6 pseudoprotein NPs and performed in vivo study of their penetration through ocular barriers using the experimental animals (wild-type C57BL/6 mice). Te in vivo study showed that the NPs are able to penetrate cornea and sclera and get even into the retina.…”