Maria Teresa Junqueira Garcia

Methylene blue (MB)-based photodynamic therapy has proven to be effective and promising for the treatment of non-melanoma skin neoplasms. However, the topi

The aim of this study was to develop an HPLC method for simultaneous quantification of metformin (MET) and methylene blue (MB) in in vitro skin permeation/retention studies, in which retention was evaluated in the different layers of the skin [stratum corneum (SC) and the viable epidermis + dermis (VE + D)]. The method was validated considering the following parameters: specificity, linearity, quantitation limit (LOQ), recovery, precision and accuracy. Calibration curves were obtained using the following six matrices: methanol, water, methanolic extracts from the SC and VE + D spiked with the drugs and drugs extracted from the SC and VE + D. The precision, accuracy and LOQ of the method were evaluated in water and in VE + D and SC, applying the drug extraction process. The results show that the method is selective and linear for both drugs. The precision and accuracy values, independent of matrix and drug, were below the limit of 15%. The LOQ of MB was defined as 0.4 μg/ml in the VE + D and SC and 0.8 μg/ml in water. The LOQ of MET was defined as 0.8 μg/ml in the VE + D and SC and 0.4 μg/ml in the water. The recovery of the method was adequate, consistent and reproducible for the concentration range of 0.4–10 μg/ml for MB (73.3–92.1%) and 0.8–10.0 μg/mL for MET (72.4–94.4%). This method has a potential application in the development of formulation for skin delivery of MB and MET.

To achieve an efficient skin penetration of most compounds it is necessary to overcome the barrier function of the skin, provided mainly (but not only) by the stratum corneum. Among various strategies used or studied to date, chemical penetration enhancers are the most frequently employed with one of the longest histories of use. There is a multitude of agents described as penetration enhancers, and they present varying properties and structures. In this manuscript, we aim to provide a brief overview of traditional enhancers and some of their properties, focusing on the benefits of combination of chemical enhancers and on selected novel compounds that have shown promise to increase drug delivery into/across the skin.

Considering that most inflammatory diseases occur locally and near the body surface, transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) may be an interesting strategy for delivering these drugs directly to the diseased site. To optimize ketoprofen (KP) transdermal delivery we investigated the influence of dioleylphosphatidylcholine (DOPC) on skin permeation. The formulations studied were: i) a physical mixture of KP and DOPC and ii) DOPC and KP complex, in a molar ratio of 1:3, obtained by dissolution of the components in chloroform followed by drying under a N₂ atmosphere. Both systems were dispersed in mineral oil and the in vitro percutaneous was assayed by absorption using a flow through diffusion cell. Differential Scanning Calorimetry (DSC) and ¹H NMR studies were carried out to characterize KP and DOPC interactions. Geometry optimizations using Density Functional Theory and semiempirical methods, as well as a flexible docking procedure were carried out to obtain a binding model for KP with DOPC. KP solubility and partition studies in the formulations, as well as skin irritation and hypersensitivity assays were also carried out. DSC determinations in the complex showed enthalpy and temperature depressions, indicating KP and DOPC interaction. In addition, dipole–dipole interactions between the KP carboxylic acid and OH groups in phospholipids were shown by ¹H NMR studies. Based on the NMR studies, a KP–DOPC binding model is proposed, in which KP is involved by the two long aliphatic chains of the phospholipid. Solubility studies indicated that DOPC improved drug solubility. KP permeation was enhanced by both formulations tested, but the complex also increased its skin uptake. Such behavior could be attributed to the solubilizing, melting and enhancing effects of DOPC. Skin irritation and hypersensitivity were not significantly changed compared to control, suggesting that the formulation may be therapeutically explored for KP transdermal delivery.