Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies

L Bonilla-Vidal; M Espina; M L García; L Baldomà; J Badia; J A González; L M Delgado; A Gliszczyńska; E B Souto; E Sánchez-López

doi:10.1016/j.ijpharm.2024.124222

Novel nanostructured lipid carriers loading Apigenin for anterior segment ocular pathologies

Int J Pharm. 2024 May 11:658:124222. doi: 10.1016/j.ijpharm.2024.124222. Online ahead of print.

Authors

L Bonilla-Vidal¹, M Espina¹, M L García¹, L Baldomà², J Badia², J A González³, L M Delgado⁴, A Gliszczyńska⁵, E B Souto⁶, E Sánchez-López⁷

Affiliations

¹ Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, University of Barcelona, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain.
² Department of Biochemistry and Physiology, University of Barcelona, 08028 Barcelona, Spain; Institute of Biomedicine of the University of Barcelona (IBUB), Institute of Research of Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain.
³ Department of Endodontics, Faculty of Dentistry, International University of Catalonia (UIC), 08195 Barcelona, Spain.
⁴ Bioengineering Institute of Technology, International University of Catalonia (UIC), 08028 Barcelona, Spain.
⁵ Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
⁶ REQUIMTE/UCIBIO, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
⁷ Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, University of Barcelona, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN(2)UB), University of Barcelona, 08028 Barcelona, Spain; Unit of Synthesis and Biomedical Applications of Peptides, IQAC-CSIC, 08034 Barcelona, Spain. Electronic address: esanchezlopez@ub.edu.

PMID: 38735632
DOI: 10.1016/j.ijpharm.2024.124222

Abstract

Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation.

Keywords: Apigenin; Lipid nanoparticles; Nanostructured lipid carriers; Rosehip oil.