Hydrogels for diabetic eyes: Naltrexone loading, release profiles and cornea penetration

• Published in: Materials Science & Engineering C 2019-12, Vol.105, p.110092-110092, Article 110092
• Main Authors: Alvarez-Rivera, Fernando, Serro, Ana Paula, Silva, Diana, Concheiro, Angel, Alvarez-Lorenzo, Carmen
• Format: Article
• Language: English
• Subjects: Acrylic acid; Animals; Aqueous solutions; Binding sites; Cattle; Chick Embryo; Chorioallantoic membrane; Complications; Contact lenses; Controlled release; Cornea; Cornea - metabolism; Cornea - pathology; Corneal diseases; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Diabetes mellitus; Diabetic eye complications; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Drug delivery systems; Dry eye; Eye (anatomy); Flow chambers; Growth factors; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogels - pharmacology; Imprinted hydrogels; Irritation; Materials science; Mesenchyme; Microfluidics; Mimicry; Monomers; Naltrexone; Naltrexone - chemistry; Naltrexone - pharmacokinetics; Naltrexone - pharmacology; Opioid growth factor; Opioid receptors; Permeability; Polyhydroxyethyl methacrylate; Stem cells; Sterilization; Sustained release; Ultrasonic testing
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.110092

Naltrexone (NTX) is a potent opioid growth factor receptor (OGFR) antagonist proved to be useful for treatment of ocular surface complications. The aim of this work was to explore the feasibility of designing NTX-imprinted 2-hydroxyethyl methacrylate-based hydrogels for sustained drug release on the ocular surface. Acrylic acid (AAc) and benzyl methacrylate (BzMA) were chosen as functional monomers able to form binding cavities mimicking OGFR binding sites for NTX. Imprinted hydrogels containing functional monomers loaded higher amounts of NTX compared to non-imprinted ones by simple soaking in drug aqueous solution. In addition, possibility of carrying out the loading and sterilization processes in one step was investigated. NTX release was evaluated both under agitated sink conditions and in a microfluidic flow chamber mimicking the hydrodynamic conditions of the eye, namely the small volume of lachrymal fluid and its renovation rate. Sustained release profiles together with adequate swelling degree (46 to 57% w/w), light transparency (over 85%) and oxygen permeability may make these hydrogels suitable candidates to NTX-eluting contact lenses. NTX-loaded and non-loaded discs successfully passed the chorioallantoic membrane test for potential ocular irritation and were cytocompatible with human mesenchymal stem cells. Finally, NTX-imprinted hydrogels tested in the bovine corneal permeability assay provided therapeutically relevant amounts of NTX inside the cornea, reaching drug levels similar to those attained with a concentrated aqueous solution in spite the discs showed sustained release. [Display omitted] •Acrylic acid (AAc) played a main role in forming naltrexone binding points.•The imprinting enhanced drug loading, which could be carried out during autoclaving.•Sustained release was recorded in both agitated sink medium and microfluidic chamber.•Imprinted hydrogels provided therapeutic drug amounts inside the cornea.