# Steering the Clinical Translation of Delivery Systems for Drugs and Health Products
## 3 Poster Presentations
### Contact Lenses with Bioinspired Receptors for Naltrexone, an Antidiabetic Drug  
[PERSON] 1, [PERSON] 2,3, [PERSON] 3, [PERSON] 1 and [PERSON] 1,*  
1 Departamento de Farmacologia, Farmacia y Tecnologia Farmaceutica, I+D Farma (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain  
2 Centro de Investigacao Interdisciplinar Egas Moniz, Instituto Universitario Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal  
3 Centro de Quimica Estrutural, Instituto Superior Tecnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal  
* Correspondence: [EMAIL_ADDRESS]  
Diabetes causes relevant metabolic changes that trigger ocular surface complications such as decreased tear production, diminished corneal sensitivity, and delayed wound healing. The natural opioid growth factor (OGF) enkephalin has been found to be at higher levels in persons with diabetes compared to healthy people, causing increased susceptibility to ulceration and infection due to delayed epithelialization during wound healing. Thus, antagonists of its receptor (OGFr), such as naltrexone (NTX), may revert enkephalin-dependent ocular surface complications [64]. Repeated doses of NTX as eye drops have been shown to be safe, but poorly efficient. Thus, the aim of this work was to design hydrogels suitable as soft CLs that can load therapeutic amounts of NTX and provide sustained release on the ocular surface.  
Poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels were endowed with affinity for NTX by mimicking the functional groups and conformation of OGFr. Several hydrogels were prepared with functional monomers bearing carboxylic acid groups (acrylic acid, AAc) and aromatic groups (benzyl methacrylate, BzMA). It was hypothesized that the addition of NTX before polymerization may drive the adequate spatial arrangement of the monomers for a more efficient formation of ad hoc artificial  
Figure 19: In vitro cell migration (expressed as % closure of the gap versus time) in scratched nasal epithelium cell layer: (red) formulation, (green) control.  
receptors (imprinted hydrogels) [65]. Both imprinted and non-imprinted hydrogels were washed and then loaded by soaking in NTX aqueous solutions. Imprinted hydrogels containing AAc mers loaded up to \(10.83\pm 0.38\) mg NTX/g. Feasibility of carrying out loading and sterilization (autoclaving) processes in one step was confirmed. NTX-loaded hydrogels were highly cytocompatible with human mesenchymal stem cells (hMSC) and passed the HET-CAM test.  
NTX release was recorded using both a conventional test in bulk medium (sink conditions) and a microfluidic device mimicking lachrymal fluid turn over [65]. The bioinspired hydrogels showed sustained release for 24-48 h under sink conditions and much more prolonged release when the microfluidic chamber was used. Interestingly, the hydrogels with higher affinity for NTX in the loading test were also the ones that sustained better the release in any setup used. Finally, ex vivo corneal tests revealed that NTX mainly accumulated into the cornea at therapeutic levels, with minor permeation to the receptor compartment simulating the aqueous humor. Thus, NTX-eluting hydrogels may represent a promising tool to locally address eye complications of diabetes mellitus.  
This work was supported by MINECO [SAF2017-83118-R], Agencia Estatal de Investigacion (AEI) Spain, Xunta de Galicia [ED431C 2016/008] and FEDER.