HYDROGEL-BASED OPHTHALMIC CONTACT LENSES CONTAINING AMPHOTERICIN B: STATISTICAL OPTIMIZATION AND PHYSICO-CHEMICAL CHARACTERIZATION
Hydrogel; keratitis fungal; contact lenses; amphotericin B.
Cornea Fungal infections are among the main causes of blindness in the world. The drawbacks displayed by formulations used to treat these diseases are contributing factors for the establishment of this worriesome scenario. Among such biopharmaceutical limitations, one could mention the low absorption and retention of the drug in the target tissue, which results in a poor local bioavailability and, by consequence, therapeutic failure. Therefore, the aim of this work was to develop hydrogels based on poly (vinyl alcohol) (PVA) containing amphotericin B (AmB) to be used as therapeutic contact lenses. For this purpose, a central composite design (CCD) was used, wherein the influence of the sodium hydroxide concentration ([NaOH]), temperature (Cº) and STMP concentration were assessed regarding the degree of swelling response (GI %) and encapsulation efficiency (EE %). In addition, mathematical models were developed to predict the behavior of the response variables, as well as to determine the necessary formulation parameters to obtain a system with desirable characteristics to the ocular route. The chosen formulation was characterized in terms of swelling kinetics, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and transmittance. Hydrogels with GI % between 125 to 181 and EE % between 39 to 72 were obtained. Additionally, it was possible to determine that only [NaOH] demonstrated a significant effect on the response variables. Accordingly, an appropriate model predictive for GI % and EE % was obtained. Additionally, the characterization results showed that the crosslinking reaction was effective. This was inferred by the absence of the characteristic peaks of the phosphate ring from STMP in the FTIR spectra. FTIR and DCS analyses demonstrated that AmB is probably located between the polymeric networks of the hydrogel. Therefore, it was possible to infer that the developed contact lenses are potential candidates to become a new therapeutic alternative for the delivery and drug release modulation directly in the cornea. These results suggest that this formulation could display an increase in therapeutic effectiveness and possible compliance compared to traditional ocular formulations.