Touch-actuated microneedle array patch for closed-loop transdermal drug delivery

Yang, Jingbo; Chen, Zhipeng; Rui, Yong; Li, Jiyu; Lin, Yinyan; Gao, Jie; Ren, Lei; Liu, Bin; Jiang, Lelun

doi:10.1080/10717544.2018.1507060

Cited by 42 publications

(24 citation statements)

References 56 publications

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“…However, stratum corneum is the biggest obstacle to skin penetration for TDDSs. To weaken the barrier effect of stratum corneum, various methods have been developed to promote skin penetration, including those changing drug properties (liposome [7], ethosomes [8], solid lipid nanoparticles [9], microemulsion and cell-penetrating peptides [10,11]), adding chemical enhancers [12] (azone [13], surfactants [14] and terpenes [15]), and applying physical means (ultrasonic import [16], laser import [17], microneedle [18] and cupping therapy [19]). Ethosomes and microneedles are both relatively effective ways to promote penetration.…”

Section: Introductionmentioning

confidence: 99%

Microneedle-Assisted Percutaneous Delivery of Paeoniflorin-Loaded Ethosomes

Cui

Zhang

et al. 2018

Molecules

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Paeoniflorin, the main component of total glucosides of paeony (TGP), shows good therapeutic effects in arthritis, but has low bioavailability when administered orally. Avoiding such a deficiency for topical administration would expand its clinical application. This study aimed to avoid these limitations by using nanotechnology (ethosomes) and a physical approach (microneedles). Paeoniflorin-loaded ethosomal formulation (TGP-E) was optimized and evaluated in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), polydispersity index (PDI) and morphology. TGP-E was prepared by the hot injection method and optimized by single-factor tests and an orthogonal experimental design. The optimized paeoniflorin-loaded ethosomes had EE of 27.82 ± 1.56%, PS of 137.9 ± 7.57 nm with PDI of 0.120 ± 0.005, ZP of −0.74 ± 0.43 mV. Ethosomes showed a nearly spherical shape under the transmission electron microscope (TEM). The optimal microneedle-assisted (MN-assisted) conditions were obtained at a microneedle length of 500 μm, a pressure of 3 N and an action time of 3 min. The cumulative penetration amounts (Qn) of TGP solution transdermal (ST) and MN-assisted TGP solution transdermal (MST) were 24.42 ± 8.35 μg/cm2 and 548.11 ± 10.49 μg/cm2, respectively. Qn of TGP-E transdermal (PT) and MN-assisted TGP-E transdermal (MPT) were 54.97 ± 4.72 μg/cm2 and 307.17 ± 26.36 μg/cm2, respectively. These findings indicate that use of ethosomes and microneedles can both enhance the penetration ofpaeoniflorin, but for the water-soluble drug, there is no obvious synergism between nanotechnology and microneedles for enhancing penetration in a transdermal drug delivery system.

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Section: Introductionmentioning

confidence: 99%

Microneedle-Assisted Percutaneous Delivery of Paeoniflorin-Loaded Ethosomes

Cui

Zhang

et al. 2018

Molecules

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“…Li et al reported the enhanced permeation of drugs into the skin by pretreatment with a solid polymer microneedle 51 . Although the preforming of holes is simple and practical, the holes in the stratum corneum are not stable 52 , 53 because of the physical closure due to the elasticity of skin tissue. Figure 2e shows the DC resistance of the arm skin of two subjects monitored during the placement and removal of a PMN.…”

Section: Resultsmentioning

confidence: 99%

Transdermal electroosmotic flow generated by a porous microneedle array patch

et al. 2021

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A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.

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“…1b and Video S1. Furthermore, owing to the recovery ability of the skin, the created microholes gradually shrink and self-heal to closure after MA removal 41 . One of the key advantages of this design is that the users can repeat the abovementioned P&R processes to reopen the microholes for a new round of drug administration, resulting in longlasting positive diffusion and active iontophoresis.…”

Section: Drug Delivery Mechanismmentioning

confidence: 99%

“…Above all, the smartphone-powered IMAP can achieve four-drug administration strategies, including drug diffusion across intact skin, drug diffusion across poked skin, drug diffusion and iontophoresis across intact skin, and drug diffusion and iontophoresis across poked skin. The administration strategy of drug diffusion across poked skin using a touch-actuated MA patch was reported in our previous work 41 . Compared with the other four administration methods, the insulin-loaded touch-actuated MA patch exhibited the best hypoglycemic effect.…”

Section: Drug Delivery Mechanismmentioning

confidence: 99%

Smartphone-powered iontophoresis-microneedle array patch for controlled transdermal delivery

Yang

Rui

et al. 2020

Microsyst Nanoeng

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The incidence rate of diabetes has been increasing every year in nearly all nations and regions. The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain and potential infections. While microneedle arrays (MAs) have emerged as painless delivery techniques, the integration of MA systems with electronic devices to precisely control drug delivery has rarely been realized. In this study, we developed an iontophoresis-microneedle array patch (IMAP) powered by a portable smartphone for the active and controllable transdermal delivery of insulin. The IMAP in situ integrates iontophoresis and charged nanovesicles into one patch, achieving a one-step drug administration strategy of “penetration, diffusion and iontophoresis”. The MA of the IMAP is first pressed on the skin to create microholes and then is retracted, followed by the iontophoresis delivery of insulin-loaded nanovesicles through these microholes in an electrically controlled manner. This method has synergistically and remarkably enhanced controlled insulin delivery. The amount of insulin can be effectively regulated by the IMAP by applying different current intensities. This in vivo study has demonstrated that the IMAP effectively delivers insulin and produces robust hypoglycemic effects in a type-1 diabetic rat model, with more advanced controllability and efficiency than delivery by a pristine microneedle or iontophoresis. The IMAP system shows high potential for diabetes therapy and the capacity to provide active as well as long-term glycemic regulation without medical staff care.

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Touch-actuated microneedle array patch for closed-loop transdermal drug delivery

Cited by 42 publications

References 56 publications

Microneedle-Assisted Percutaneous Delivery of Paeoniflorin-Loaded Ethosomes

Microneedle-Assisted Percutaneous Delivery of Paeoniflorin-Loaded Ethosomes

Transdermal electroosmotic flow generated by a porous microneedle array patch

Smartphone-powered iontophoresis-microneedle array patch for controlled transdermal delivery

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