Microneedle Arrays for Drug Delivery - Peptide Delivery Challenge
The use of microneedles (MN) is very promising in the field of vaccination being currently under clinical trials, namely for influenza or polio (1). MNs assure an epi/dermal diffusion of antigens promoting robust immune response in comparison to conventional injection (2). We aim to apply MNs as a tool for the administration of peptides in the context of multiple sclerosis (MS). MS is an autoimmune and neurodegenerative disease with no cure. State of the art research seeks to re-establish immunological tolerance by challenging the immune system with specific peptides or nanoparticles, showing some degree of success (3). My means of MN arrays, we propose to deliver these peptides to the epidermal space to restore immune tolerance.
Taking advantage of microfabrication process, we designed and produced 33X33 silicon MN arrays containing sharp MN with about 650 µm height and 200 µm diameter. This silicon master was applied to produce poly(dimethylsiloxane) (PDMS) molds that subsequently were used to obtain polymeric biodegradable MN arrays. Poly(vinyl acetate) (PVA) and poly(vinyl pyrrolidone) (PVP) were selected as polymer mixture for MN composition. PLP139-151 (proteolipid protein) was used as peptide of interest in the context of MS.
The results show that the MN arrays can homogeneously perforate an in vitro skin model – agarose 3%. When testing drug release in phosphate buffer at 37ºC, using fluorescent model molecules (fluorescein and rhodamine 6G), it was found the needles immediately release their content (2hrs). Using a clinically relevant peptide, it was found that 250 µg of PLP are loaded in the MN patch (quantification by high pressure liquid chromatography (HPLC)). Further experiments are being conducted in order to characterize the MN performance in vivo, as this is a clinically relevant amount of peptide to induce immunological tolerance in MS.
(1). www.clinical trials.org
(2). Koutsonanos et al. Sci Rep (2012) 2: 357.
(3). Hess et al. Adv Funct Mat (2017) 27:1700290.
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