Self-dissolving microneedles for the percutaneous absorption of EPO in mice

Ito, Yoshiaki; Yoshimitsu, Jun-Ichiro; Shiroyama, K; Sugioka, Nobuyuki; Takada, Kanji

doi:10.1080/10611860600785080

Cited by 125 publications

(44 citation statements)

References 43 publications

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“…These BA values are lower than the value of 82.1-99.4% obtained in our previous experiment, where pen-type micropiles were used in mice. 17) In the case of pen-type micropiles, an applicator was used to insert the micropile completely into the skin. Therefore an extremely high extent of BA (EBA) was obtained in the mice experiment.…”

Section: Discussionmentioning

confidence: 99%

“…When microneedle arrays are inserted into the skin, conduits are created for the penetration of drug across stratum corneum (SC). Once a drug penetrates the SC, it can diffuse rapidly through the deeper tissue and permeate into the underlying capillaries for systemic absorption.Our previous studies suggest that macromolecules such as insulin, 15,16) erythropoietin (EPO), 17,18) interferon, 19) and recombinant human growth hormone 20) are well absorbed through rat skin by self-dissolving micropile preparations about 2-3 mm in length with an outer diameter of 0.3-0.4 mm. In addition, a self-dissolving micropile array (SDMA), comprising 10 lines and 10 columns, was formed on a 1.0-cm 2 chip, where water-soluble thread-forming polymers such as chondroitin sulfate and dextran were used as the base and insulin was formulated as a model peptide drug.…”

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confidence: 99%

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Self-Dissolving Micropile Array Chip as Percutaneous Delivery System of Protein Drug

Ito

Hasegawa

Fukushima

et al. 2010

Biological & Pharmaceutical Bulletin

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Transdermal drug delivery systems (TDDS) have been challenged to increase the permeation rate of drugs through the skin and experimental strategies have included the use of chemical enhancers and physical methods. Of these, chemical enhancers have contributed most to the development of TDDS. Approximately 20 products of TDDS were launched on the US market by the end of 2008. Thus the penetration of small molecules through the skin can be enhanced by chemical enhancers.1) However, triggering of skin irritation and other safety concerns limit their use. As examples of physical absorption enhancement methods, iontophoresis, electroporation, and ultrasound have been investigated.2-6) Iontophoresis uses an electric field to drive ionized molecules across the skin by electrophoresis and nonionized molecules by electroosmosis. Despite concerns about skin irritation, iontophoresis may be useful for delivery of some peptides including insulin. 7) In particular, TDDS of lidocaine by iontophoresis was launched onto the US market in 2004. Also, transient enhancement of skin permeability of both small drugs and macromolecules has been shown by electroporation and ultrasound. 8,9) Recent advances in microfabrication technology have made it possible to prepare microneedles that have a possible application as novel TDDS. Since the first publication by Henry et al. 10) in 1998, microfabrication techniques for the production of silicon, metal, glass and polymer microneedle arrays with micrometer dimensions have been reported. [11][12][13][14] The microneedles are either solid or hollow and possess a geometrical shape. Microneedle TDDS are roughly defined by a micron-sized needle preparation through and by which drug is percutaneously administered. Microneedle TDDS are classified as follows: (1) extremely small needles through which drug solution can be injected into the skin; (2) metallic and/or silastic microneedles on whose surface drug is coated; and (3) metallic and/or silastic microneedles with which conduits (micropores) are made on the skin and drug solution is applied after removing the microneedles. Fully to understand the function of microneedles, the physiology of the skin must be considered. There are no blood vessels in the epidermis. Deeper, there are blood capillaries in the dermis, which forms the bulk of skin volume and contains living cells and nerves. When microneedle arrays are inserted into the skin, conduits are created for the penetration of drug across stratum corneum (SC). Once a drug penetrates the SC, it can diffuse rapidly through the deeper tissue and permeate into the underlying capillaries for systemic absorption.Our previous studies suggest that macromolecules such as insulin, 15,16) erythropoietin (EPO), 17,18) interferon, 19) and recombinant human growth hormone 20) are well absorbed through rat skin by self-dissolving micropile preparations about 2-3 mm in length with an outer diameter of 0.3-0.4 mm. In addition, a self-dissolving micropile array (SDMA), comprising 10 lines and 10 columns, was...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Self-Dissolving Micropile Array Chip as Percutaneous Delivery System of Protein Drug

Ito

Hasegawa

Fukushima

et al. 2010

Biological & Pharmaceutical Bulletin

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“…15) In addition, high bioavailabilities (BA) were obtained for recombinant human growth hormone (rhGH), 87.5%, in rats 16) and for erythropoietin (EPO), 82.1-99.4%, in mice. 17) The relative BA of interferon (IFN) against a subcutaneous injection of IFN solution was 79.9-117.8% in rats.…”

Section: Application Of Dissolving Microneedles To Glucose Monitoringmentioning

confidence: 99%

Application of Dissolving Microneedles to Glucose Monitoring through Dermal Interstitial Fluid

Ito

Taniguchi

Hayashi

et al. 2014

Biological & Pharmaceutical Bulletin

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Dissolving microneedles (DMs) were applied to glucose monitoring in the dermal interstitial fluid (ISF) of rats and their potential as an alternative blood glucose monitoring device was evaluated. Sodium chondroitin sulfate was used to prepare DM array chips, which consisted of 300 DMs/cm 2 . The mean length of the DMs was 475 18 µm and the mean diameter of the basement was 278 8 µm. After DMs were inserted into the skin of the hair-removed rat abdomen, a wet unwoven cloth containing 10-30 µL of water was placed on the skin and ISF was extracted. By increasing the absorbed amount of water on the unwoven cloth from 10 to 30 µL, the extracted amount of glucose increased from 1. Approximately 250 million people in Japan have diabetes, which is associated with damage to the heart, kidneys, eyes and central nervous system. 1) Diabetic patients should frequently monitor their blood glucose levels, about six times a day, in order to maintain appropriate blood glucose levels. Patients use needles to obtain blood samples from their fingers and blood glucose levels are measured with an enzyme assay method. However, this method is invasive and causes pain. In addition, concerns regarding infectious diseases often reduce the frequency by which patients take blood samples. Therefore, the development of a non-invasive method for blood glucose monitoring is desired. Transcutaneous spectroscopic methods have been reported previously, 2,3) however, electromagnetic energy is almost entirely absorbed by skin tissue. Therefore, the reliability of these electronic technologies is insufficient. Although ultrasound, 4) reverse iontophoresis, 5) and electroporation 6) have also been examined as non-invasive methods to monitor glucose levels, they have not yet been clinically introduced because of skin damage, pain, and low accuracy.Microneedle technology is attracting attention as an alternative method for non-invasive glucose monitoring. 7,8) Microneedles (MNs) were originally designed to percutaneously deliver drugs into the systemic circulation and have been classified into four categories 9,10) : (i) hollow type MNs, extremely small needles through which drug solutions are injected into the skin, (ii) coating type MNs, made of metallic and/or silastic substances, on which surface drugs are coated, (iii) pierce type MNs, made of metallic and/or silastic microneedles, through which microconduits are made in the skin followed by the application of drug solutions and/or cream after removal of the MNs, and (iv) dissolving microneedles (DMs), made of soluble polymers such as sodium chondroitin sulfate, dextran, and sodium hyaluronic acid, on which drug molecules are formulated as a solid dispersion.11,12) Of these, pierce type MNs, made of glass and plastic, have been used to monitor blood glucose levels. An MN array was stamped on the skin and interstitial fluid (ISF) was obtained by applying negative pressure, 200-500 mmHg.13) Thus, ISF could be collected without pain using a microneedle array, and glucose monitoring was performed with...

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“…Likewise, formation of microneedles of calcein, insulin, erythropoietin and l-carnitine showed good bioavailability and stability (Table 3). [32,65,67,68] …”

Section: Bioactive Macromolecules (Biopharmaceuticals)mentioning

confidence: 99%

Microneedles: an emerging transdermal drug delivery system

Bariya

Gohel

Mehta

et al. 2011

Journal of Pharmacy and Pharmacology

319

207

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Objectives One of the thrust areas in drug delivery research is transdermal drug delivery systems (TDDS) due to their characteristic advantages over oral and parenteral drug delivery systems. Researchers have focused their attention on the use of microneedles to overcome the barrier of the stratum corneum. Microneedles deliver the drug into the epidermis without disruption of nerve endings. Recent advances in the development of microneedles are discussed in this review for the benefit of young scientists and to promote research in the area. Key findings Microneedles are fabricated using a microelectromechanical system employing silicon, metals, polymers or polysaccharides. Solid coated microneedles can be used to pierce the superficial skin layer followed by delivery of the drug. Advances in microneedle research led to development of dissolvable/degradable and hollow microneedles to deliver drugs at a higher dose and to engineer drug release. Iontophoresis, sonophoresis and electrophoresis can be used to modify drug delivery when used in concern with hollow microneedles. Microneedles can be used to deliver macromolecules such as insulin, growth hormones, immunobiologicals, proteins and peptides. Microneedles containing 'cosmeceuticals' are currently available to treat acne, pigmentation, scars and wrinkles, as well as for skin tone improvement. Summary Literature survey and patents filled revealed that microneedle-based drug delivery system can be explored as a potential tool for the delivery of a variety of macromolecules that are not effectively delivered by conventional transdermal techniques.

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Self-dissolving microneedles for the percutaneous absorption of EPO in mice

Cited by 125 publications

References 43 publications

Self-Dissolving Micropile Array Chip as Percutaneous Delivery System of Protein Drug

Self-Dissolving Micropile Array Chip as Percutaneous Delivery System of Protein Drug

Application of Dissolving Microneedles to Glucose Monitoring through Dermal Interstitial Fluid

Microneedles: an emerging transdermal drug delivery system

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