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Transdermal delivery represents a very attractive administration route that provides various advantages over other methods of administration, including enhanced patient compliance via non-invasive, painless and simple application and reduced side effects. Thereby, the research on suitable drugs for this route continues to increase. However, most of drug candidates face the challenges of low drug permeability across the skin's biologically active barrier – the stratum corneum (SC). In this context, a low cost, simple screening tool to evaluate penetration of drug candidates in a human SC barrier model was developed. The in vitro model is based on a modified phospholipid vesicle-based permeation assay (PVPA) with a lipid composition close to human SC layer. The new SC PVPA model can be stored up to 2 weeks at −20 °C, withstand a pH range from 2.0 to 8.0 and the presence of co-solvents (DMSO, oleic acid and cremophor®) without losing their integrity. The human mimicking SC PVPA model was able to detect calcein permeability differences when different drugs, applied in the therapy of skin-related diseases, were present. The obtained data correlated well with the well accepted pig ear model, which highlights the potential of this new human SC model. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) is an immunosuppressant frequently used in the therapy of autoimmune disorders, including skin-related diseases. Aiming towards topical delivery, CsA was successfully incorporated into lipid nanoparticles of Lipocire DM and Pluronic F-127 using the hot homogenization method. Two different nanocarriers were optimized: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) where oleic acid was the liquid lipid. The developed nanoparticles showed mean sizes around 200 nm, a negative surface charge, and drug entrapment efficiencies around 85% and 70% for SLNs and NLCs, respectively. The spherical CsA-loaded lipid nanoparticles were stable for 9 weeks when stored at room temperature, and exhibited in vitro pH-dependent release under skin mimetic conditions, following the Peppas–Korsmeyer model. CsA, when loaded in SLNs, was safe to be used up to 140 μg mL−1 in fibroblasts and keratinocytes, while CsA-loaded NLCs and free drug exhibited IC50 values of 55 and 95 μg mL−1 (fibroblasts) and 28 and 30 μg mL−1 (keratinocytes), respectively. The developed SLNs were able to retain the drug in pork skin with a reduced permeation rate in relation to NLCs. These findings suggest that SLNs are a potential alternative to produce stable and safe CsA nanocarriers for topical administration. [ABSTRACT FROM AUTHOR]

The use of functional excipients such as ionic liquids (ILs) and the encapsulation of drugs into nanocarriers are useful strategies to overcome poor drug solubility. The aim of this work was to evaluate the potential of IL-polymer nanoparticle hybrid systems as tools to deliver poorly soluble drugs. These systems were obtained using a methodology previously developed by our group and improved herein to produce IL-polymer nanoparticle hybrid systems. Two different choline-based ILs and poly (lactic-co-glycolic acid) (PLGA) 50:50 or PLGA 75:25 were used to load rutin into the delivery system. The resulting rutin-loaded IL-polymer nanoparticle hybrid systems presented a diameter of 250–300 nm, with a low polydispersity index and a zeta potential of about −40 mV. The drug association efficiency ranged from 51% to 76%, which represents a good achievement considering the poor solubility of rutin. No significant particle aggregation was obtained upon freeze-drying. The presence of the IL in the nanosystem does not affect its sustained release properties, achieving about 85% of rutin released after 72 h. The cytotoxicity studies showed that the delivery system was not toxic to HaCat cells. Our findings may open a new paradigm on the therapy improvement of diseases treated with poorly soluble drugs. [ABSTRACT FROM AUTHOR]

(1) Background: Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical phase of drug development. (2) Methods: The interactions of a drug candidate for clinical use (licofelone) with a membrane model system made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated by combining Langmuir isotherms, Brewster angle microscopy (BAM), polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and grazing-incidence X-ray diffraction (GIXD) measurements. (3) Results: Licofelone caused the expansion of the DPPC isotherm without changing the lipid phase transition profile. Moreover, licofelone induced the reduction of DPPC packing density, while increasing the local order of the DPPC acyl chains. (4) Conclusions: The licofelone-induced alterations in the structural organization of phosphatidylcholine monolayers may be related to its pharmacological actions. Thus, the combination of studying drug-membrane interactions with the pharmacological characterization that occurs in the preclinical stage may gather additional information about the mechanisms of action and toxicity of drug candidates. Ultimately, the addition of this innovative step shall improve the success rate of drug development. [ABSTRACT FROM AUTHOR]