Pharmacokinetic and Pharmacodynamic Evaluation of Insulin Dissolving Microneedles in Dogs

Fukushima, Keizo; Yamazaki, Takenao; Hasegawa, Ryo; Ito, Yoshiaki; Sugioka, Nobuyuki; Takada, Kanji

doi:10.1089/dia.2009.0176

Cited by 39 publications

(22 citation statements)

References 55 publications

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“…In fact, despite the different materials and technologies developed so far for the fabrication of microneedles for transdermal applications, [3][4][5][6][7][8][9][10][11][12][13][14][15][16] only few works deal with needles featuring both density and size values that are comparable to those of the microneedles reported in this work. 24 View Online usually concern arrays of microneedles that feature density at least two orders of magnitude lower and size at least one order of magnitude higher than the ones reported in this work.…”

Section: Insertion Tests In Skin-like Polymersmentioning

confidence: 96%

A minimally invasive microchip for transdermal injection/sampling applications

et al. 2012

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The design, fabrication, and characterization of a minimally invasive silicon microchip for transdermal injection/sampling applications are reported and discussed. The microchip exploits an array of silicon-dioxide hollow microneedles with density of one million needles cm(-2) and lateral size of a few micrometers, protruding from the front-side chip surface for one hundred micrometers, to inject/draw fluids into/from the skin. The microneedles are in connection with independent reservoirs grooved on the back-side of the chip. Insertion experiments of the microchip in skin-like polymers (agarose hydrogels with concentrations of 2% and 4% wt) demonstrate that the microneedles successfully withstand penetration without breaking, despite their high density and small size, according to theoretical predictions. Operation of the microchip with different liquids of biomedical interest (deionized water, NaCl solution, and d-glucose solution) at different differential pressures, in the range 10-100 kPa, highlights that the flow-rate through the microneedles is linearly dependent on the pressure-drop, despite the small section area (about 13 μm(2)) of the microneedle bore, and can be finely controlled from a few ml min(-1) up to tens of ml min(-1). Evaporation (at room temperature) and acceleration (up to 80 g) losses through the microneedles are also investigated to quantify the ability of the chip in storing liquids (drug to be delivered or collected fluid) in the reservoir, and result to be of the order of 70 nl min(-1) and 1300 nl min(-1), respectively, at atmospheric pressure and room temperature.

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Section: Insertion Tests In Skin-like Polymersmentioning

confidence: 96%

A minimally invasive microchip for transdermal injection/sampling applications

et al. 2012

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“…Hyaluronic acid-based microneedles had a relative physiologic activity (RPA) of 94%-98% (Liu et al, 2012), whereas chondroitin sulfate microneedles had a RPA of 91%-100% compared with subcutaneous insulin solution (Ito et al, 2012). In dogs, for similar types of chondroitin sulfate microneedles, the RPA value was 59%-71% of subcutaneous insulin solution (Fukushima et al, 2010). Dissolving microneedles also have been studied for delivery of other peptides such as desmopressin with fast absorption (absorption half-life 14 minutes) and high bioavailability (90%-93%) (Fukushima et al, 2011).…”

Section: A Development Challenges Of Peptide Delivery Formulationsmentioning

confidence: 99%

“…Dissolving microneedles also have been studied for delivery of other peptides such as desmopressin with fast absorption (absorption half-life 14 minutes) and high bioavailability (90%-93%) (Fukushima et al, 2011). Peptides were chemically stable for at least 1 month of storage at +4°C (Fukushima et al, 2010(Fukushima et al, , 2011 or at room temperature (Ito et al, 2012;Liu et al, 2012).…”

Section: A Development Challenges Of Peptide Delivery Formulationsmentioning

confidence: 99%

Novel Delivery Systems for Improving the Clinical Use of Peptides

et al. 2015

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“…FITC-dextran and FITC-insulin were formulated into chondroitin dissolving microneedles and the dissolution kinetics was observed by a fluorescent videomicroscopic analysis. Fluorescent labeled dissolving microneedles dissolved within 3 min after insertion into the rat skin (Fukushima et al, 2010(Fukushima et al, , 2011. As the base polymer of dissolving microneedles, chondroitin sulfate was used.…”

Section: Discussionmentioning

confidence: 99%