Pseudoprotein-based nanoparticles show promise as carriers for ophthalmic drug delivery

Abstract

Drug delivery used to treat ocular disease still poses a challenge to modern ophthalmology. Well-established intravitreal inje-ctions im- ply discomfort to the patients and risk of ocular complications. Therefore, opportunities to deliver drugs by topical administration are investigated thoroughly. Despite its seemingly easy accessibility, the eye is well protected by efficient mecha-nisms that rapidly remove drugs after instillation on the eye surface. Hence, eye drops are less effective for the treatment of vari-ous diseases, which necessitates a risk-containing procedure of intravitreal injection. One of the rational ways to overcome the problem is the application of drug-loaded polymeric nanoparticles (NPs) that are able to penetrate through ocular barriers when administered topically. Pseudo-proteins (PPs) - amino acid-based biodegradable polymers are one of the most suitable materials for the design of drug delivering NPs. One of the most important features of such kind of nanovehicles is “disappearance” from the body after their function is fulfilled. We have prepared biodegradable NPs of various types by nanoprecipitation of the PEA-class of PP composed of L-leucine, 1,6-hexanediol and sebacic acid (8L6). The originally designed arginine-based cationic PEA and comb-like PEA containing lateral PEG-2000 chains along with 8L6 anchoring fragments in the backbones were used to construct positively charged and PEGylated NPs. The NPs were loaded with fluorescein diacetate (FDA) as a fluorescent probe to detect if the NP penetrated through the ocular barriers. A preliminary in vivo study on intraocular infiltration of the NPs has been done using wild-type C57BL/6 mice. After penetrating into the cellular lysosomes, FDA probes became visible due to the hydrolysis of the diacetate groups, thus allowing for the detection of the NPs as tiny fluorescent spots inside the tissues. One day after admini-stration, fluorescent dots were found at various sites - always in the peripheral cornea and the sclera, and in different layers of the outer retina depending on the type of NPs used. Four days after administration, fluorescent dots were still visible in the peripheral cornea and the sclera with some of the NPs. These results show that the new type of NPs infiltrate the ocular tissues after topical administration and are taken up by the cells. This raises hope that the NPs may be useful carriers for ocular delivery of thera-peutic agents.