Percorrer por autor "Pinto, Carlos 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.
- Hydrogel dressings loaded with anticancer/antimicrobial Ag(I) camphorimine complexes for treatment of malignant woundsPublication . Costa, Joana P.; Silva, Diana C.; Marques, Fernanda; Muazeia, Jeremias; Leitão, Jorge H.; Pinto, Carlos A.; Saraiva, Jorge A.; Serro, Ana P.; Carvalho, M. Fernanda N. N.The treatment of skin wounds caused by metastatic lesions is often difficult because not many medicines exist that simultaneously act on cancer cells and bacteria. Such difficulty delays and sometimes compromises the treatment of oncologic patients. To contribute to face that problem a set of silver camphorimine compounds with antibacterial properties were assessed for activity against cancer cells A375 and MeWo melanoma cells using the MTT assay. From them, the silver camphorimine complex 1 displayed the highest combined anticancer and antibacterial activities and therefore was incorporated in a HEMA-based hydrogel to be used in a wound dressing. The hydrogel disks loaded with complex 1 effectively reduced suspensions of E. coli, P. aeruginosa and B. contaminans from the initial 5 × 105 CFU/mL to 0 CFU/mL after 24 and 48 h of incubation. In the case of S. aureus, a reduction of more than 99 % was observed after 24 h. However, after 48 h of incubation, the hydrogel was ineffective towards S. aureus. Although presenting a non-porous structure, the hydrogel revealed to be hydrophilic and able to retain a significant water content, allowing to keep the wound moist. Additionally, it exhibited mechanical and mucoadhesive properties suitable for treatments involving repeated and frequent dressing changes. The hydrogels were loaded with complex 1 by soaking and then sterilized by high hydrostatic pressure (HHP). Biocompatibility studies demonstrated that the loaded dressings were non-irritant and hemocompatible. The sterilization procedure did not affect the integrity of the complex, nor the drug release, which occurred in a sustained way through a non-Fickian diffusion mechanism. The dressing released 618.5 mg/cm2/24 h, with nearly 90 % of the release occurring within the first 8 h. Considering the exudate production rates of chronic wounds and the MIC and MBC values for complex 1 it is expected that the dressings will be effective as antibacterial and anticancer agents. In vivo studies will be needed to confirm the clinical potential of the dressings. However, the produced dressings offer a promising approach for both infection control and cancer therapy in chronic wounds.
- 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.
- Low friction hydrogel with diclofenac eluting ability for dry eye therapeutic contact lensesPublication . Silva, Diana C.; Oliveira, Margarida; Marto-Costa, Carolina; Teixeira, João; Oom, Madalena Salema; Pinto, Carlos A.; Saraiva, Jorge A.; Marques, Ana Clara; Fitzhenry, Laurence; Serro, Ana PaulaWhen placed in the eye, contact lenses (CLs) disturb the tear fluid and affect the natural tribological behaviour of the eye. The disruption in the contact mechanics between the ocular tissues can increase frictional shear stress and ocular dryness, causing discomfort. Ultimately, continuous CLs wear can trigger inflammation which is particularly critical for people suffering from dry eye. In this work, a double strategy was followed to obtain therapeutic daily disposable CLs for dry eye: a hydroxyethyl methacrylate (HEMA) based hydrogel was coated with two natural polysaccharides, chitosan (CHI) and hyaluronic acid (HA) and posteriorly loaded with an anti-inflammatory drug (diclofenac, DCF). Material sterilisation was carried out by high hydrostatic pressure (HHP) combined with moderate temperature. The friction coefficient (μ) was determined in the presence of different tear biomolecules (cholesterol, lysozyme and albumin) using a nanotribometer. Drug release experiments were performed in static and in hydrodynamic conditions. The material was extensively characterised, regarding surface morphology/topography, optical properties, water content and swelling behaviour, wettability, ionic and oxygen permeability and mechanical properties. It was found that the coating did not impair the physico-chemical properties relevant for the material’s application in CLs. Besides, it also ensured a sustained release of DCF for 24 h in tests performed in hydrodynamic conditions that simulate those found in the eye, increasing significantly the amount of drug released. It reduced friction, improving the lubrication ability of the hydrogel, and presented antibacterial properties against S. aureus, P. aeruginosa and B. Cereus. The coated samples did not reveal any signs of cytotoxicity or potential eye irritation. Overall, the coating of the hydrogel may be useful to produce daily CLs able to alleviate dry eye symptoms and the discomfort of CLs wearers.