The Development of Novel Dermal Translocation, High Potency Drug Delivery Systems

Jennifer Morrissey

    Research output: Types of ThesisDoctoral Thesis

    Abstract

    Transdermal drug delivery is the administration of a therapeutic drug into the skin. However, as the skin is a very effective barrier against dehydration and the passage of microbes and chemicals, drug delivery through the skin is very challenging. Transdermal drug delivery is constantly evolving with an estimated worth of $32 billion by 2015 (Paudel et al. (2010)). There are many limitations to the permeation of a drug through the skin. One large area of topically applied drug application is in the treatment of non-melanoma skin cancers (NMSC). This cancer is the number one diagnosed cancer in both men and women in Ireland followed by prostate and breast cancers respectively. The treatment of NMSC requires a targeted drug delivery approach with the concentration of drug within the epidermis and dermis critical in successfully treatment and clearance. The current leading therapy is Aldara™, a 5 % imiquimod oil and water emulsion cream. Due to high dose application there are many undesirable side effects which can lead to patient irritation/pain and non-completion of the treatment. This study compared the current treatment to novel polymeric transdermal patches and microneedles. In-vitro studies carried out in this research on Aldara™ using full thickness human skin demonstrated poor permeation of the drug over 24 h with only 4.9 ± 1.1 % of the applied dose permeating the skin. Novel lower dosage polymeric patches were fabricated using five polymers, two of which demonstrated potential following release analysis through artificial membranes. Utilising the polymers used in the fabrication of transdermal patches (PVA and PVP) polymeric microneedles were produced. The microneedles were fabricated with 5 % of the drug loading of Aldara™. In-vitro analysis through full thickness human skin was carried out on the novel patches and the microneedles. The novel PVP patches and microneedle arrays demonstrated similar retention within the epidermis and increased retention in the dermis compared to Aldara™. These drug delivery devices with their combination of lower dose, reduced waste and targeted delivery holds significant advantages for the patient care and have commercial potential for the treatment of NMSC.  Keywords: Transdermal, imiquimod, polymeric patches, drug delivery, microneedles, skin permeation
    Original languageEnglish
    Awarding Institution
    Supervisors/Advisors
    • Hughes, Helen, Supervisor
    • O'Reilly, Niall, Supervisor
    • Mc Loughlin, Peter, Supervisor
    Publication statusUnpublished - 2014

    Keywords

    • Transdermal, imiquimod, polymeric patches, drug delivery, microneedles, skin permeation

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