Abstract
Drug delivery via the skin is attractive, but it is challenging and thus it is an area of continual research. Challenges arise in this field because only a narrow range of drugs naturally diffuse into the cutaneous tissue. This natural passive skin diffusion process is largely dictated by the drugs physicochemical characteristics. Only moderately lipophilic, low molecular weight agents accumulate in sufficient concentrations in the systemic circulation after topical delivery to elicit a clinical effect. The inability of drugs to pass into the skin has been addressed in previous work through chemical and physical methods of penetration enhancement, but using the currently available technologies it remains problematic to force compounds through the skin without damaging the tissue. The aim of this project was to investigate if the application of topical hypobaric pressure, a new physical technique to enhance topical drug delivery, could be used to facilitate drug delivery into the skin without skin damage.To study the effect of local hypobaric pressure changes upon drug penetration into the skin three model systems were selected based on their different physicochemical properties; minoxidil (a small drug that passes into the skin via the hair follicles), dextran (a model macromolecule), and nanosized carriers (to simulate a drug delivery system). Application of the device (built-in-house) gave a stable pressure reading for 60 min. Histology, showed hypobaric pressure up to 400 ± 50 mBar did not damage the skin. The application of hypobaric pressure (400 ± 50 mbar) was shown to be significantly (P < 0.05) enhance drug deposition in the skin for the majority of test systems. For example, an enhancement ratio of 16.5, 5.3 and 5.2 was observed for minoxidil in stratum corneum, epidermis and dermis respectively. For solid lipid nanoparticles an enhancement ratio of 1.2, 8.8 and 7.8 was recorded for stratum corneum, epidermis and dermis respectively. For the dextran (FD-4) the enhancement ratios were 2.9, 2.0 and 1.2 for stratum corneum, epidermis and dermis respectively. The hypobaric enhanced skin permeation was dependent on the test systems size, surface charge, and hydrophobicity. Confocal microscope images showed the solid lipid nanoparticle enhancement was through the intercellular and follicular pathways, whereas the dextran enhancement was through the intercellular pathway when hypobaric pressure was applied. In conclusion the results obtained from this project suggested that the application of hypobaric pressure was an effective, safe and promising method to enhance the delivery of drugs into the skin and it warrants further assessment in vivo to enable its clinical use.
| Date of Award | 1 Oct 2019 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Stuart Jones (Supervisor) & Andrew Chan (Supervisor) |