Development of Peptide Targeted PLGA-PEGylated Nanoparticles Loading Licochalcone-A for Ocular Inflammation.

Ruth Galindo,Miren Ettcheto,María Luisa García,Marta Espina,Amanda Cano,Antoni Camins,María José Gómara,Isabel Haro,Elena Sánchez-López

doi:10.3390/pharmaceutics14020285

Abstract

Licochalcone-A is a natural compound with anti-inflammatory properties. However, it possesses low water solubility, making its application for the treatment of ocular inflammation difficult. To overcome this drawback, biodegradable nanoparticles incorporating Licochalcone-A have been developed. Additionally, to avoid fast clearance and increase cellular internalization into the ocular tissues, PLGA nanoparticles have been functionalized using PEG and cell penetrating peptides (Tet-1 and B6). To optimize the formulations, a factorial design was carried out and short-term stability of the nanoparticles was studied. Moreover, morphology was also observed by transmission electron microcopy and in vitro drug release was carried out. Ocular tolerance of the formulations was ensured in vitro and in vivo and anti-inflammatory therapeutic efficacy was also assessed. Surface functionalized nanoparticles loading Licochalcone-A were developed with an average size below 200 nm, a positive surface charge, and a monodisperse population. The formulations were non-irritant and showed a prolonged Licochalcone-A release. Despite the fact that both Licochalcone-A Tet-1 and B6 functionalized nanoparticles demonstrated to be suitable for the treatment of ocular inflammation, B6 targeted nanoparticles provided greater therapeutic efficacy in in vivo assays.

Highlights

One of the most prevalent conditions in ophthalmology is ocular inflammation
The inflammation process triggers the production of growth factors and cytokines and stimulates the enzyme phospholipase A2 (PLA2), which leads to the synthesis of eicosanoids from a phospholipid found in cell membranes, arachidonic acid (AA)
PLGA surface was functionalized with poly(ethylene glycol) (PEG) and custom-synthesized cell-penetrating peptides (CPPs) obtaining two formulations: Lico-A PLGA-PEG-Tet1 NPs and Lico-A PLGA-PEG-B6 NPs

Summary

Introduction

One of the most prevalent conditions in ophthalmology is ocular inflammation. This inflammation constitutes the local response of ocular tissues and annexes against an external or internal insult. This process may be able to produce irreversible damage to the ocular function [1]. The inflammation process triggers the production of growth factors and cytokines and stimulates the enzyme phospholipase A2 (PLA2), which leads to the synthesis of eicosanoids from a phospholipid found in cell membranes, arachidonic acid (AA). AA can stimulate the production of pro-inflammatory cytokines and initiate apoptosis. AA-derived eicosanoids regulate immunopathological and inflammatory processes through different physiological responses, vascular homeostasis, and platelet aggregation [2]

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