Percorrer por autor "Saraiva, Jorge A."
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- Dexamethasone phosphate and penetratin co-eluting contact lenses : a strategy to enhance ocular drug permeabilityPublication . Toffoletto, Nadia; Salema-Oom, Madalena; Nicoli, Sara; Pescina, Silvia; González-Fernández, Felipe M.; Pinto, Carlos A.; Saraiva, Jorge A.; Matos, António P. Alves de; Vivero-Lopez, Maria; Huete-Toral, Fernando; Carracedo, Gonzalo; Saramago, Benilde; Serro, Ana PaulaContact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.
- Improved triamcinolone acetonide-eluting contact lenses based on cyclodextrins and high hydrostatic pressure assisted complexationPublication . Marto-Costa, Carolina; Toffoletto, Nadia; Salema-Oom, Madalena; Antunes, Alexandra M.M.; Pinto, Carlos A.; Saraiva, Jorge A.; Silva-Herdade, Ana S.; Alvarez-Lorenzo, Carmen; Serro, Ana PaulaContact lenses (CLs) constitute an advantageous platform for the topical release of corticosteroids due to their prolonged contact with the eye. However, the lipophilic nature of corticosteroids hampers CLs' ability to release therapeutic amounts. Two approaches to improve loading and release of triamcinolone acetonide (TA) from poly(2-hydroxyethyl methacrylate)-based hydrogels were investigated: adding 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to the monomers solution before polymerization (HEMA/i-CD) and an hydrogels' post-treatment with HP-β-CD (HEMA/p-CD). The effect of HP-β-CD and sterilization by high hydrostatic pressure (HHP) on the hydrogel properties (water content, oxygen and ion permeability, roughness, transmittance, and stiffness) was evaluated. The HEMA/i-CD hydrogels had stronger affinity for TA, sustaining its release for one day. HHP sterilization promoted the formation of cyclodextrin-TA complexes within the hydrogels, improving their drug-loading capacity »60 %. Cytotoxicity and irritability tests confirmed the safety of the therapeutic CLs. TA released from the hydrogels permeated through ocular tissues ex vivo and showed anti-inflammatory activity. Finally, a previously validated mathematical model was used to estimate the ability of the TA-loaded CLs to deliver therapeutic drug concentrations to the posterior part of the eye. Overall, HP-β-CD-containing CLs are promising candidates for the topical ocular application of TA as an alternative delivery system to intraocular injections.