The greatest achievement in the advanced drug delivery field should be the optimization of non-invasive formulations for the delivery of high molecular weight compounds. Peptides, proteins, and other macromolecules can have poor membrane permeation, principally due to their large molecular weight. The aim of this work was to explore the possibility of administering fluorescently labeled dextrans (molecular weight 4–150 kDa) across the buccal mucosa. Permeation experiments across pig esophageal mucosa were carried out using fatty acids and bile salts as penetration enhancers. The data obtained show that it is possible to increase or promote the mucosa permeation of high molecular weight dextrans by using caprylic acid or sodium taurocholate as the chemical enhancers. With these enhancers, dextrans with molecular weight of 70 and 150 kDa, that in passive conditions did not permeate, could cross the mucosa in detectable amounts. FD-70 and FD-150 showed comparable permeability values, despite the molecular weight difference. The results obtained in the present work suggest that the buccal administration of high molecular weight compounds is feasible.
An innovative and sensitive HPLC-UV method for the extraction and quantification of methotrexate (MTX) in skin layers was developed and validated. Owing to the physico-chemical characteristics of the drug and the nature of the tissue, it was necessary to use folic acid (FA) as an internal standard for MTX quantification in the dermis. MTX (and FA) analysis was performed on a Phenomenex Jupiter C 18 column, using a 50 mM sodium acetate buffer (pH 3.6) and methanol mixture (87:13, v/v) as mobile phase, pumped at 1 ml/min. The absorbance was monitored at 290 nm. The method was selective, linear in the range 0.11-8.49 μg/ml for extraction solvent and 0.05-8.94 μg/ml for pH 7.4 phosphate-buffered saline, precise and accurate, with lower limits of quantitation of 0.11 μg/ml (extraction solvent) and 0.05 μg/ml (pH 7.4 phosphate-buffered saline). The method developed is suitable for the quantification of MTX in skin layers at the end of in vitro permeation experiments; the overall mass balance was 96.5 ± 1.4%, in line with the requirements of the Organisation for Economic Co-operation and Development guideline for the testing of the chemicals (Skin absorption: in vitro method).
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