RESUMO
This study aimed to explore the use of chemical and physical enhancement strategies for the intradermal delivery of cromolyn sodium (CS) for treatment of atopic dermatitis. CS gels were formulated to individually contain 2.5 and 9% salcaprozate sodium (SNAC) as a potential chemical enhancer. The effect of microneedles, alone and in combination with SNAC, was investigated via in vitro permeation studies. Skin impedance and FTIR evaluation of SNAC-treated stratum corneum (SC) was done and compared to the control. The amount of drug delivered in the dermis after 24 h by the 2.5% and 9% SNAC gels was 23.29 ± 1.89 µg/cm2 and 35.87 ± 2.23 µg/cm2, respectively, which were significantly higher than the control (p < 0.05) but were not remarkably different from each other (p > 0.05). Microneedles enhanced permeation in both the control and 2.5% SNAC groups (p < 0.05); however, no synergistic enhancement was observed when microneedle and SNAC treatments were combined (p > 0.05). Over 24 h of treating the SC with 2.5% SNAC, FTIR evaluation showed stretches on the CH2 asymmetric and symmetric stretching vibrations observed at 2920.23 cm-1 and 2850.79 cm-1 respectively in untreated SC, which shifted to higher wavenumbers and indicated some lipid fluidizing effect. However, no significant drop in skin impedance was seen with SNAC as compared to the control (p > 0.05). SNAC was concluded to have skin permeation enhancement effect on CS, while microneedles effectively enhanced CS permeation even in the absence of SNAC.
Assuntos
Cromolina Sódica , Absorção Cutânea , Administração Cutânea , Géis/metabolismo , Agulhas , Pele/metabolismoRESUMO
Cromolyn sodium (CS) is a mast cell stabilizer administered to treat allergic diseases. A topical system would sustain its delivery and may be designed for treatment of atopic dermatitis. Established HPLC protocols for detection of CS are time consuming and intensive, indicating the need for a more streamlined method. This study aimed at developing and validating a sensitive and selective LC-MS method for quantifying CS in skin permeation studies that was less time and resource demanding. The optimized method involved an isocratic mobile phase (10 mM NH4HCO3, pH 8.0, 90% and ACN, 10%) at a flow rate of 0.25 mL/min. Detection involved direct MS/MS channels with m/z 467.0255 (precursor) and m/z 379.0517 (fragment) using argon as the collision gas. CS calibrants were prepared in PBS, pH 7.4, and methanol for validation (0.1-2.5 µg/mL). To ensure no skin interference, dermatomed porcine skin was mounted on Franz diffusion cells that were analyzed after 24 h. The skin layers were also separated, extracted in methanol, and analyzed using the developed method. Retention time was 1.9 min and 4.1 min in methanol and buffer, respectively. No interfering peaks were observed from the receptor and skin extracts, and linearity was established between 0.1 and 2.5 µg/mL. Interday and intraday accuracy and precision were within the acceptable limit of ±20% at the LLOQ and ±15% at other concentrations. Overall, the simplified, validated method showed sensitivity in detecting CS in skin without interference and was applied to demonstrate quantification of drug in skin following 4% cromolyn sodium gel exposure.
