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Título: | Cell penetrating peptides-functionalized Licochalcone-A-loaded PLGA nanoparticles for ocular inflammatory diseases: Evaluation of in vitro anti-proliferative effects, stabilization by freeze-drying and characterization of an in-situ forming gel |
Autor: | Galindo-Camacho, Ruth M.; Haro Villar, Isabel CSIC ORCID ; Gómara Elena, María José CSIC ORCID; Espina, Marta; Fonseca, Joel; Martins-Gomes, Carlos; Camins, Antoni; Silva, Amélia M.; García, María L.; Souto, Eliana B. | Palabras clave: | PLGA nanoparticles Cell penetrating peptide Freeze-drying; In-situ forming gel Licochalcone-A Ocular anti-inflammatory |
Fecha de publicación: | 26-abr-2023 | Editor: | Elsevier | Citación: | International Journal of Pharmaceutics 639: 122982 (2023) | Resumen: | Licochalcone-A (Lico-A) PLGA NPs functionalized with cell penetrating peptides B6 and Tet-1 are proposed for the treatment of ocular anti-inflammatory diseases. In this work, we report the in vitro biocompatibility of cell penetrating peptides-functionalized Lico-A-loaded PLGA NPs in Caco-2 cell lines revealing a non-cytotoxic profile, and their anti-inflammatory activity against RAW 264.7 cell lines. Given the risk of hydrolysis of the liquid suspensions, freeze-drying was carried out testing different cryoprotectants (e.g., disaccharides, alcohols, and oligosaccharide-derived sugar alcohol) to prevent particle aggregation and mitigate physical stress. As the purpose is the topical eye instillation of the nanoparticles, to reduce precorneal wash-out, increase residence time and thus Lico-A bioavailability, an in-situ forming gel based on poloxamer 407 containing Lico-A loaded PLGA nanoparticles functionalized with B6 and Tet-1 for ocular administration has been developed. Developed formulations remain in a flowing semi-liquid state under non-physiological conditions and transformed into a semi-solid state under ocular temperature conditions (35 °C), which is beneficial for ocular administration. The pH, viscosity, texture parameters and gelation temperature results met the requirements for ophthalmic formulations. The gel has characteristics of viscoelasticity, suitable mechanical and mucoadhesive performance which facilitate its uniform distribution over the conjunctiva surface. In conclusion, we anticipate the potential clinical significance of our developed product provided that a synergistic effect is achieved by combining the high anti-inflammatory activity of Lico-A delivered by PLGA NPs with B6 and Tet-1 for site-specific targeting in the eye, using an in-situ forming gel. | Versión del editor: | https://doi.org/10.1016/j.ijpharm.2023.122982 | URI: | http://hdl.handle.net/10261/307950 | DOI: | 10.1016/j.ijpharm.2023.122982 | ISSN: | 03785173 |
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