Using Oscillation to Improve the Insertion Depth and Consistency of Hollow Microneedles for Transdermal Insulin Delivery with Mechanistic Insights

被引:0
|
作者
Smith, Fiona [1 ]
Kotowska, Anna M. [1 ]
Fiedler, Benjamin [1 ,5 ]
Cerny, Edward [2 ]
Cheung, Karmen [2 ]
Rutland, Catrin S. [3 ]
Chowdhury, Faz [2 ]
Segal, Joel [4 ]
Rawson, Frankie J. [1 ]
Marlow, Maria [1 ]
机构
[1] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England
[2] Nemaura Pharm Ltd, Adv Technol Ctr, Oakwood Dr, Loughborough LE11 3QF, England
[3] Univ Nottingham, Sch Vet Med & Sci, Nottingham NG7 2RD, England
[4] Univ Nottingham, Fac Engn, Dept Mech Mat & Mfg Engn, Nottingham NG8 1BB, England
[5] UCL, Sch Pharm, London WC1N 1AX, England
基金
英国工程与自然科学研究理事会;
关键词
microneedles; insulin; insertion; diabetes mellitus; reproducibility; oscillation; METAL MICRONEEDLES; SKIN PENETRATION; KINETICS; PAIN; INFUSION; AGGREGATION; FABRICATION; ADSORPTION; INJECTION; ADHERENCE;
D O I
10.1021/acs.molpharmaceut.4c00942
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Microneedles (MNs) offer the potential for discrete and painless transdermal drug delivery, yet poor insertion and dosing consistency have hindered their clinical translation. Specifically, hollow MNs are appropriate for the administration of liquid modalities, including insulin, which could prove to be beneficial for patients with type 1 diabetes mellitus. This work aimed to design and manufacture a hollow MN with an improved insertion and delivery profile suitable for insulin administration. Ex vivo insertion studies demonstrated that oscillation of MNs upon insertion into skin produced a favorable insertion profile, with reduced variation, compared to static MN insertion. Histological staining showed that this could be due to the repeated motion of the oscillating MN disrupting elastic fibers in the dermis. Additionally, permeation studies demonstrated that increased quantities of insulin were able to permeate the skin when oscillation was employed compared to static MN insertion. This study has shown that oscillation is a valuable tool in improving the transdermal delivery of insulin via a single hollow MN in vitro. Moving forward, in vivo studies should be completed to gain a fuller understanding of the benefits of the oscillation of MNs on transdermal drug delivery.
引用
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页数:14
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