Development of dual drug loaded-hydrogel scaffold combining microfluidics and coaxial 3D-printing for intravitreal implantation.

Autor: Zingale E; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6, 95125 Catania, Italy., Weaver E; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK., Bertelli PM; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, Northern Ireland, UK., Lengyel I; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, Northern Ireland, UK., Pignatello R; Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Viale A. Doria, 6, 95125 Catania, Italy. Electronic address: rosario.pignatello@unict.it., Lamprou DA; School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: D.Lamprou@qub.ac.uk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Nov 15; Vol. 665, pp. 124700. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1016/j.ijpharm.2024.124700
Abstrakt: Treating diabetic retinopathy (DR) effectively is challenging, aiming for high efficacy with minimal discomfort. While intravitreal injection is the current standard, it has several disadvantages. Implantable systems offer an alternative, less invasive, with long-lasting effects drug delivery system (DDS). The current study aims to develop a soft, minimally invasive, biodegradable, and bioadhesive material-based hydrogel scaffold to prevent common issues with implants. A grid-shaped scaffold was created using coaxial 3D printing (3DP) to extrude two bioinks in a single filament. The scaffold comprises an inner core of curcumin-loaded liposomes (CUR-LPs) that prepared by microfluidics (MFs) embedded in a hydrogel of hydroxyethyl cellulose (HEC), and an outer layer of hyaluronic acid-chitosan matrix with free resveratrol (RSV), delivering two Sirt1 agonists synergistically activating Sirt1 downregulated in DR. Optimized liposomes, prepared via MFs, exhibit suitable properties for retinal delivery in terms of size (<200 nm), polydispersity index (PDI) (<0.3), neutral zeta potential (ZP), encapsulation efficiency (∼97 %), and stability up to 4 weeks. Mechanical studies confirm scaffold elasticity for easy implantation. The release profiles show sustained release of both molecules, with different patterns related to different localization of the molecules. RSV released initially after 30 min with a total release more than 90 % at 336 h. CUR release starts after 24 h with only 4.78 % of CUR released before and gradually released thanks to its internal localization in the scaffold. Liposomes and hydrogels can generate dual drug-loaded 3D structures with sustained release. Microscopic analysis confirms optimal distribution of liposomes within the hydrogel scaffold. The latter resulted compatible in vitro with human retinal microvascular endothelial cells up to 72 h of exposition. The hydrogel scaffold, composed of hyaluronic acid and chitosan, shows promise for prolonged treatment and minimally invasive surgery.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: