New insights into dermal drug delivery pathways - Interplay between vehicle, active compound, and skin
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Philipps-Universität Marburg
Abstract
In this thesis, new dermal drug delivery pathways that promote the dermal penetration of active compounds using the ex vivo porcine ear model, were investigated. Classical and novel approaches clearly demonstrate the complex interplay between vehicle, active compound, and skin. Therefore, different strategies were conducted to forecast the most suitable vehicle for efficient dermal penetration of an active compound.
The first step studied the effect of massage and skin hydration on the dermal penetration behaviour of active compounds. Massage influences the hydration state of skin due to the applied pressure during the treatment. Upon massaging the dermal formulations into the skin, the skin tissues are squeezed and cause the expulsion of water from deeper layers of the SC. The expulsed water acts as a water barrier on top of the skin that prevents the penetration of lipophilic active compounds and promotes the penetration of hydrophilic active compounds.
The second part investigated the effect of vehicle type and its components on the dermal penetration behaviour of active compounds. The solvent drag mechanism as a novel dermal drug delivery pathway of active compounds was introduced. The solvent drag mechanism means that liquids, i.e., water, paraffin, penetrates into the skin and drags the active compounds being dissolved in these vehicles along with into the skin. Additionally, results introduced the micellar-assisted penetration. The micellar properties of Lanette N allow the formation of o/w micelles and the encapsulation of lipophilic active compounds into the hydrophobic core of the o/w micelles. This micellar encapsulation allow the lipophilic active compounds to enter the skin via the apolar intercellular pathway and together with the o/w micelles via the polar pathway. Additionally, this part proved, the solvent drag mechanism for lipophilic and hydrophilic active compounds loaded in multi-component vehicles, i.e., NR-loaded or SF- loaded in Lanette N-based formulations. Moreover, this part proved the influence of different surfactant types and lipid contents on the penetration behaviour of lipophilic active compounds incorporated into semi-SLN that enhanced the skin penetration. The obtained data in this part highlight the combination of different mechanism to enhance the dermal drug delivery of active compounds, i.e., passive diffusion, solvent-drag mechanism, particle-assisted penetration, micellar-assisted penetration, that are likely to occur not step-wise but superimpose each other.
The third part studied the effect of surfactant type on the dermal penetration behaviour of active compounds. This study proved the micellar-assisted penetration upon application of NR-loaded TPGS-based surfactant solutions that can therefore act as “trojan horses” for dermal drug delivery of lipophilic active compounds.
The last step assisted the effect of hygroscopic vehicles on the dermal penetration behaviour of active compounds. This study proposed the solvent pullout mechanism as a novel dermal drug delivery mechanism of hydrophilic active compounds. The dermal application of hygroscopic solvents, i.e., polyethylene glycol (PEG 400), resulted in drawing water from deeper skin layers to the SC. This creates two opposite movements of water fronts, i.e., the PEG 400 solutions penetrating from the SC surface into deeper skin layers versus the water moving from deeper skin layers skin to the SC surface. Therefore, hydrophilic active compounds, being dissolved in the PEG formulations, are pulled-out from deeper layers into the viable skin by the penetrating-out water which is pulled out due to the hygroscopic properties of PEG.
The findings of this thesis provide evidence that the Marburg ex vivo skin model is a suitable model for testing the dermal penetration efficacy of active compounds from dermal formulations. A thorough investigation of a suitable vehicle is a prerequisite for effective dermal drug delivery, and it is a fundamental step to understand the complex interplay between vehicle, active compound, and skin.
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This item has been published with the following license: In Copyright