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The skin serves as a semi-permeable barrier that protects the body from pathogens and water loss. The stratum corneum, the upper 10-15 µm layer of skin, is the primary barrier layer. Due to its structure, only drugs that are lipophilic and with a low molecular weight (<500 Da) can penetrate intact skin. This study examines the use of microdermabrasion as a method of removing the stratum corneum to increase the skin's permeability to hydrophilic molecules, proteins, and vaccines. Microdermabrasion is a FDA-approved cosmetic skin resurfacing procedure that removes the stratum by bombarding it with abrasive particles under vacuum. The aims of this thesis are focused on optimizing the microdermabrasion conditions that will selectively remove stratum corneum, evaluating the transport of different sized molecules through abraded skin in vitro, examining drug efficacy in vivo by delivering insulin to diabetic rats, and examining the rate of skin healing after treatment. Microdermabrasion can be used as a non-invasive transdermal drug technique to safely remove stratum corneum to make the skin more permeable to waters soluble drugs and proteins.

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Transdermal drug delivery system is in the centre of attention in recent years. For efficient dermal drug delivery the drug has to overcome the barrier of the outermost layer of the skin, the stratum corneum. For facilitating dermal drug transport, the barrier properties of the stratum corneum can be varied by applying chemical penetration enhancers. The aim of this work was to characterize various penetration enhancers and investigate their mechanism of action. We combined well established techniques like differential scanning calorimetry (DSC) and infrared spectroscopy (IR) with confocal Raman microscopy (CRM) as an upcoming technique in skin research. CRM offers the possibility of label-free and non- destructive, chemically selective analysis of stratum corneum lipids and proteins. We used isolated human stratum corneum for incubation with the penetration enhancers. As a novel approach, the samples of treated stratum corneum were freeze dried to avoid any discrepancies which might come up with differences in the hydratation state of stratum corneum (SC). Furthermore, the structure of lipids and proteins in the stratum corneum was analyzed. In our study, stratum corneum was treated with dimethyle sulphoxide, propylene glycol, ethylene glycol, ethylene glycol-d4 and oleic acid. We observed that...

The use of nano/meso-particles (NP/MP) as constituent of topical formulations of drug and cosmetics has been a topic of considerable interest for the past 20 years. However, the transport mechanism of nanoparticle-associated drug/active following topical application on the skin is still unclear. No general answers have been obtained to such questions as the depth of intact NP penetration into the skin, the skin distribution of active substances, and the fate of the vehicles on/in the skin. The main objective of this thesis, therefore, was to observe the in vitro penetration of fluorescently-labeled nanoparticle vehicle and “active” on/within the skin by using laser scanning confocal microscopy (LSCM). Furthermore, the concentration profile of the “active” in the outermost skin layer, stratum corneum, has been assessed by using tape stripping technique combined with HPLC analysis. The factors, including particle size, hydrophobicity, shell thickness of nanocapsules and surface charge, have been investigated with regard to their abilities to influence the penetration of “active” into the skin. The methods for NP preparation and characterization have also been developed. The results demonstrated that the delivery of “active” into the stratum corneum from NP/MP were influenced by a number a factors, including particle size, hydrophobicity, surface charge and shell thickness of capsules. The “active” delivery (i) is greater from larger vectors; (ii) increases as the hydrophobicity of NP/MP increases; (iii) is favoured by cationic NP; (iv) is favoured from capsules with a smaller shell thickness. NP vehicle and “active” mainly co-localize in skin “furrows” and around hair follicles after topical application. No evidence shows NP penetrate beyond the superficial layer of the skin. In the stratum corneum, the “active” remains in part associated with NP, but the release f the “active” clearly occurs to some extent followed by its penetration into deep layers of the stratum corneum. Overall, through this work, the fate of nanoparticle vehicle and the “active” has been distinguished and the physicochemical properties of the nanoparticles that determine their behaviour once applied to the skin, and the kinetics with which an “active” is released, has also been understood.

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