Transdermal administration of hydrophilic biopolymers
Master thesis
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http://hdl.handle.net/11250/245726Utgivelsesdato
2010Metadata
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Sammendrag
The skin provides a great hydrophobic barrier towards penetration of foreign materials into the body, which makes delivery of drugs across the skin difficult. Thus, the aim of this study was to elucidate whether the hydrophilic biopolymers alginate (G-block), chitosan, hyaluronicacid and fish gelatin could penetrate the skin and determine which skin pre-treatments, incubation periods and polymer characteristics (e.g. molecular weight, charge and hydrophobicity) needed in order to achieve successful skin penetration of these biopolymers.
The biopolymers were degraded by acid or enzymatic hydrolysis in order to produce small peptides and oligomers with different molecular weights. These were conjugated with Alexa488 fluorescent dyes. Abdominal skins from health adults after plastic surgery were used in the transdermal experiments where the epidermal side of the skin was treated with tape, acetone and microneedles in order to influence and decrease the skin barrier. The transdermal experiments were performed by the Franz diffusion cell system and fluorescent sample dissolved in dimethyl sulfoxide (DMSO) or only DMSO (control sample) was added to the epidermal side of the skin. Confocal Laser Scanning Microscope was used to visualize the penetration of biopolymers in the skin tissue. In addition, an experiment where paracetamol was applied to the skin was performed to evaluate the skin penetration kinetics.
In order to achieve successful skin penetration of the biopolymers, there was a need for 20-24 hours of incubation and extensive pre-treatment of the skin prior to the transdermal experiments. Microneedles were found to be most enhancing on skin penetration, while tapestripping was not. All of the chosen biopolymers were able to penetrate the skin, where the smallest fish gelatin peptides (Mw ≈ 1kDa) penetrated the skin with highest efficiency. Noconclusion was made regarding chitosan skin penetration due to obscure results. None of the biopolymers penetrated through the skin and entered the receptor phase, below the skin, even though they penetrated into the skin. This indicates that they may have interacted with charged components in the extracellular matrix of the skin. Paracetamol demonstrated insufficient skin penetration and no assessment were made on the ability of paracetamol to penetrate the skin. DMSO was found to be toxic to keratinocytes (skin cells) in high concentrations at constant exposure, while lower concentrations of DMSO might have proliferating effects on the keratinocytes.