title: Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution.
abstract: In this study, we used optical coherence tomography (OCT) to extensively investigate, for the first time, the effect that microneedle (MN) geometry (MN height, and MN interspacing) and force of application have upon penetration characteristics of soluble poly(methylvinylether-co-maleic anhydride, PMVE/MA) MN arrays into neonatal porcine skin in vitro. The results from OCT investigations were then used to design optimal and suboptimal MN-based drug delivery systems and evaluate their drug delivery profiles cross full thickness and dermatomed neonatal porcine skin in vitro. It was found that increasing the force used for MN application resulted in a significant increase in the depth of penetration achieved within neonatal porcine skin. For example, MN of 600μm height penetrated to a depth of 330μm when inserted at a force of 4.4N/array, while the penetration increased significantly to a depth of 520μm, when the force of application was increased to 16.4N/array. At an application force of 11.0N/array it was found that, in each case, increasing MN height from 350 to 600μm to 900μm led to a significant increase in the depth of MN penetration achieved. Moreover, alteration of MN interspacing had no effect upon depth of penetration achieved, at a constant MN height and force of application. With respect to MN dissolution, an approximate 34% reduction in MN height occurred in the first 15min, with only 17% of the MN height remaining after a 3-hour period. Across both skin models, there was a significantly greater cumulative amount of theophylline delivered after 24h from an MN array of 900μm height (292.23±16.77μg), in comparison to an MN array of 350μm height (242.62±14.81μg) (p<0.001). Employing full thickness skin significantly reduced drug permeation in both cases. Importantly, this study has highlighted the effect that MN geometry and application force have upon the depth of penetration into skin. While it has been shown that MN height has an important role in the extent of drug delivered across neonatal porcine skin from a soluble MN array, further studies to evaluate the full significance of MN geometry on MN mediated drug delivery are now underway. The successful use of OCT in this study could prove to be a key development for polymeric MN research, accelerating their commercial exploitation.
authors: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. r.donnelly@qub.ac.uk
authors: Ryan F
authors: RF
authors: Donnelly
authors: Martin J
authors: MJ
authors: Garland
authors: Desmond I J
authors: DI
authors: Morrow
authors: Katarzyna
authors: K
authors: Migalska
authors: Thakur Raghu Raj
authors: TR
authors: Singh
authors: Rita
authors: R
authors: Majithiya
authors: A David
authors: AD
authors: Woolfson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004058:Diffusion; D004337:Drug Carriers; D004867:Equipment Design; D007271:Injections, Intradermal; D008298:Maleates / Q000737:chemistry / Q000378:metabolism*; D008845:Microinjections; D008904:Miniaturization; D009339:Needles; D010539:Permeability; D011095:Polyethylenes / Q000737:chemistry / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D013552:Swine; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D041623:Tomography, Optical Coherence
chemical_list: D004337:Drug Carriers; D008298:Maleates; D011095:Polyethylenes; C043105:poly(methyl vinyl ether-co-maleic anhydride); D013806:Theophylline