Percorrer por autor "Chauhan, Anuj"
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- Asymmetry in drug permeability through the corneaPublication . Toffoletto, Nadia; Chauhan, Anuj; Alvarez-Lorenzo, Carmen; Saramago, Benilde; Serro, Ana PaulaThe permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release systems.
- Controlled release of antibiotics from vitamin E–loaded silicone-hydrogel contact lensesPublication . Paradiso, Patrizia; Serro, Ana Paula; Saramago, Benilde; Colaço, Rogério; Chauhan, AnujSymptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs. We specifically focus on increasing the release duration of levofloxacin and chlorhexidine from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS® contact lenses by incorporating vitamin E diffusion barriers. Results show that 20% of vitamin E loading in the contact lens increases the release duration of levofloxacin to 100 h and 50 h from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS®, respectively, which is a 3- and 6-fold increase, respectively, for the 2 lenses. For chlorhexidine, the increase is 2.5- and 10-fold, for the TrueEye™ and OASYS®, respectively, to 130 h and 170 h. The mass of drug loaded in the lenses can be controlled to achieve a daily release comparable to the commonly prescribed eye drop therapy. The vitamin E–loaded lenses retain all critical properties for in vivo use.
- A physiology-based mathematical model to understand drug delivery from contact lenses to the back of the eyePublication . Toffoletto, Nadia; Saramago, Benilde; Serro, Ana Paula; Chauhan, AnujObjective: Therapeutic contact lenses, able to store drug and deliver it to the eye surface in a sustained fashion, gained interest as an effective and patient-friendly alternative to eye drops. Recent animal studies also demonstrated the presence of therapeutic drug levels in the back of the eye after wearing drug-loaded contact lenses, thus opening the possibility of treating the posterior segment without need of invasive intraocular injections. The drug pathways from contact lenses to the back of the eye require further investigation. Methods: A mechanistic mathematical model was developed to evaluate the drug concentration over time in the tears, sclera and choroid, retina, aqueous humor and vitreous humor after the application of a therapeutic contact lens. The main drug transport mechanisms of the eye and the barrier properties of the different tissues were included in the model. Validation was performed by comparison with experimental data in literature. Results: The model predictions of drug concentration over time reflected the experimental data both in the anterior and posterior segment of the eye. The model can differentiate between contributions to transport from different pathways. Conclusions: The model constitutes a first step towards the possibility of predicting the ocular drug distribution and the treatment efficacy in the early stage of contact lens development, and it may help reduce both the need for in vivo tests (with ethical and economic advantages) and the gap between the lens design and clinical application. It also allows for an improved understanding of drug transport in the eye.