Development of Novel Transdermal Drug Delivery Technologies for Therapeutic Peptides

Colin Dillon

    Research output: Types of ThesisDoctoral Thesis

    Abstract

    The enormously rich chemical and biological diversity of peptides makes them extremely exciting targets as therapeutic entities. Delivery of these biologically active drugs is limited, however, to mainly parenteral intravenous injection or infusion which limits their potential, particularly for the treatment of less severe conditions. Transdermal drug delivery is an attractive proposition given that it represents a non-invasive means of administering pharmaceuticals. The highly effective barrier properties provided by the stratum corneum (SC), however, limits the application of transdermal delivery to relatively small, lipophilic molecules. A dissolving microneedle system was developed using a combination of biocompatible polymers and stabilising sugars. In order to avoid loss of drug activity, the formulation process was carried out in aqueous solutions and at ambient temperatures. A variety of characterisation techniques were carried out and, with the aid of statistical analysis, an optimum polymer/sugar formulation was selected. Further characterisation work was carried out to examine needle strength, needle sharpness, drug diffusion within the array matrix, skin penetration and the stability of a model peptide, polymyxin B, encapsulated in the formulation. Franz diffusion cells were then used to carry out in vitro diffusion studies utilising porcine skin. These studies demonstrated that the microneedle system successfully delivered the peptide drug-load without loss of activity. In addition, 2 synthesised analogues of existing therapeutic peptides were also incorporated into the microneedle arrays and subsequently delivered through porcine skin to examine the effectiveness of the microneedle system to deliver peptides of various sizes and chemical properties. Finally, a sustained drug release system based on the dissolving microneedle formulation was investigated which incorporated drug loaded polylactic-co-glycolic acid (PLGA) particles into the PVP/trehalose microneedles. These arrays were subsequently characterised and skin diffusion testing carried out to determine the ability of the microneedles to deliver the particles through porcine skin. Drug release studies were also carried out to examine the release profile of polymyxin B encapsulated in the PLGA particles.
    Original languageEnglish
    Awarding Institution
    Supervisors/Advisors
    • Hughes, Helen, Supervisor
    • O'Reilly, Niall, Supervisor
    Publication statusUnpublished - 2017

    Keywords

    • Novel Transdermal Drug Delivery Technologies, Therapeutic Peptides

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