Effect of Microneedle Geometry and Supporting Substrate on Microneedle Array Penetration into Skin

Kochhar, Jaspreet Singh; Quek, Ten Cheer; Soon, Wei Jun; Choi, Jinseok; Zou, Shui; Kang, Lifeng

doi:10.1002/jps.23724

Cited by 142 publications

(95 citation statements)

References 30 publications

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“…The high density of microneedle arrays may also diminish the penetration capability (29,30). It was found that >5× base MNs provided the best penetration capability in human skin (29,30). This, along with our finding that a 5× base MNs offers lesion-free delivery, argues strongly that 5× base MNs would be ideal for vaccine delivery, but such less dense MNs would further limit the loading capacity of biodegradable MNs.…”

Section: Discussionmentioning

confidence: 73%

See 1 more Smart Citation

Effective and lesion-free cutaneous influenza vaccination

Wang

2015

Proc. Natl. Acad. Sci. U.S.A.

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The current study details efficient lesion-free cutaneous vaccination via vaccine delivery into an array of micropores in the skin, instead of bolus injection at a single site. Such delivery effectively segregated vaccine-induced inflammation, resulting in rapid resolution of the inflammation, provided that distances between any two micropores were sufficient. When the inoculation site was treated by FDA-approved nonablative fractional laser (NAFL) before insertion of a PR8 model influenza vaccine-packaged, biodegradable microneedle array (MNs), mice displayed vigorous antigenuptake, eliciting strong Th1-biased immunity. These animals were completely protected from homologous viral challenges, and fully or partially protected from heterologous H1N1 and H3N2 viral challenges, whereas mice receiving MNs alone suffered from severe illnesses or died of similar viral challenges. NAFL-mediated adjuvanicity was ascribed primarily to dsDNA and other "danger" signals released from laser-damaged skin cells. Thus, mice deficient in dsDNA-sensing pathway, but not Toll like receptor (TLR) or inflammasome pathways, showed poor responses to NAFL. Importantly, with this novel approach both mice and swine exhibited strong protective immunity without incurring any appreciable skin irritation, in sharp contrast to the overt skin irritation caused by intradermal injections. The effective lesion-free cutaneous vaccination merits further clinical studies.biodegradable microneedle | nonablative fractional laser | dsDNA S ubstantial evidence has shown that skin is a more potent site for vaccination than muscle because the former contains a large number of antigen presenting cells (APCs) and abundant network of lymphatic vessels. Moreover, skin offers potential for painless, needle-free, and self-applicable immunization, which would particularly benefit annual influenza vaccination of large populations (1, 2). However, skin immunization has not been broadly adopted to date, due to lack of safe adjuvants and technical difficulties in injecting vaccines into the ultrathin (<2 mm) skin tissue (3,4). We have demonstrated that controllable skin injury can serve as safe "adjuvant" for cutaneous vaccination and similar observations have been also made by other investigators (5-7). Treatment of the inoculation site with nonablative fractional laser (NAFL) generates an array of microthermal zones (MTZs) beneath the stratum corneum (8). The dying cells in the MTZs release "danger" signals that provoke sterile inflammation that is however constrained within individual MTZs. This array of microsterile inflammatory zones is resolved quickly, effectively averting skin lesion, provided that affected and unaffected areas of the skin are adequately balanced (8). Importantly, despite fast resolution, the microinflammation zones prove sufficient in augmentation of adaptive immune responses against the vaccine (5). In addition, this standalone adjuvant does not affect the volume of administration or formulation of the vaccine, which are serious hurdles for...

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Section: Discussionmentioning

confidence: 73%

“…Our present study showed that a 2× base bacillus CalmetteGuérin-MNs provoked severe skin irritation. The high density of microneedle arrays may also diminish the penetration capability (29,30). It was found that >5× base MNs provided the best penetration capability in human skin (29,30).…”

Section: Discussionmentioning

confidence: 99%

Effective and lesion-free cutaneous influenza vaccination

Wang

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The use of a coloured dye, such as methylene blue [51,52] or trypan blue [53,54,55], has been widely used by many MN groups to act as en face visual confirmation of MN penetration. These dyes selectively stain cells of the viable epidermis and not the SC, therefore successfully identifying MNcreated microchannels [45].…”

Section: Staining Of Microneedle-treated Skinmentioning

confidence: 99%

“…It has been used solely to demonstrate MN piercing or more commonly used as a quick qualitative test before analysing the skin via a different method to provide more information [5]. Gomaa et al [53] visualised MN pre-treated skin stained with trypan blue and monitored pre-treated skin via TEWL technology, as illustrated in Figure 6 a. Kochhar et al [54] used the same dye to stain the perforations and also confirmed pore formation using histological cryosectioning. This post-penetration staining can be used to provide some estimates of the pore diameter by measuring the diameter of the dye spot.…”

Section: Staining Of Microneedle-treated Skinmentioning

confidence: 99%

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

Lutton

Moore

Larrañeta

et al. 2015

Drug Deliv. and Transl. Res.

109

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“…blocking of MN holes, not easy for self-administration). Polymeric MNs composed of water-soluble polymers are difficult to insert fully in the skin due to their geometries and inferior mechanical strength (Kochhar et al, 2013;Larrañeta et al, 2014;Lee et al, 2011). As a result they present incomplete insertion leading to ineffective drug delivery and material waste.…”

Section: Introductionmentioning

confidence: 99%

Inkjet printing of transdermal microneedles for the delivery of anticancer agents

Uddin

Scoutaris

Klepetsanis

et al. 2015

International Journal of Pharmaceutics

159

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A novel inkjet printing technology is introduced as a process to coat metal microneedle arrays with three anticancer agents 5-fluororacil, curcumin and cisplatin for transdermal delivery. The hydrophilic graft copolymer Soluplus® was used as a drug carrier and the coating formulations consisted of drug -polymer solutions at various ratios. A piezoelectric dispenser jetted microdroplets on the microneedle surface to develop uniform, accurate and reproducible coating layers without any material losses. Inkjet printing was found to depend on the nozzle size, the applied voltage (mV) and the duration of the pulse (s). The drug release rates were determined in vitro using Franz type diffusion cells with dermatomed porcine skin. The drug release rates depended on the drug-polymer ratio, the drug lipophilicity and the skin thickness. All drugs presented increased release profiles (750 m skin thickness), which were retarded for 900 m skin thickness. Soluplus assisted the drug release especially for the water insoluble curcumin and cisplatin due to its solubilizing capacity. Inkjet printing was proved an effective technology for coating of metal microneedles which can then be used for further transdermal drug delivery applications.

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Effect of Microneedle Geometry and Supporting Substrate on Microneedle Array Penetration into Skin

Cited by 142 publications

References 30 publications

Effective and lesion-free cutaneous influenza vaccination

Effective and lesion-free cutaneous influenza vaccination

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

Inkjet printing of transdermal microneedles for the delivery of anticancer agents

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