Incidence of low bioavailability of leuprolide acetate after percutaneous administration to rats by dissolving microneedles

Ito, Yoshiaki; Murano, Hiroshi; Hamasaki, Noriyuki; Fukushima, Keizo; Takada, Kanji

doi:10.1016/j.ijpharm.2011.01.039

Cited by 52 publications

(34 citation statements)

References 40 publications

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“…Drawing methods of fabrication have also been used with polymer/sugar melts and polymer/sugar solutions. Various materials including CMC [113–114], chondroitin sulfate [115–123], dextran [117, 122, 124], dextrin [117, 125–126], PVP [127–130], PVA [129–131], PLGA [44, 132], fibroin [133] and sugars [134] have been dissolved in water, filled into the mold cavities and allowed to dry, sometimes with the additional use of vacuum and/or centrifugal force.…”

Section: Fabrication Of Microneedlesmentioning

confidence: 99%

Microneedles for drug and vaccine delivery

Kim

Park

Prausnitz

2012

Advanced Drug Delivery Reviews

1,355

1,036

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Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications.

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Section: Fabrication Of Microneedlesmentioning

confidence: 99%

Microneedles for drug and vaccine delivery

Kim

Park

Prausnitz

2012

Advanced Drug Delivery Reviews

1,355

1,036

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“…Recent focus has shifted from making metal-based microneedles to developing microneedles made of bio- [11] Parathyroid hormone (1-34) 4 Coated microneedles [12], [13] Insulin 6 Hollow microneedles [3,[14][15][16][17] Dissolvable microneedles Solid microneedles Lysozyme 14.3 Dissolvable (polymer) microneedles [18] Human growth hormone 22 Hollow microneedles [19][20][21] Dissolvable (polymer) microneedles Bovine serum albumin 66 Dissolvable (polymer) microneedles [22] Human immunoglobulin 1500 Dissolvable (sugar) microneedles [23] Solid (metal-based) microneedles [18]. Simple modifications of drug loading and patch design allowed these microneedles to deliver a bolus dose or controlled release of the drug.…”

Section: Dissolving Microneedlesmentioning

confidence: 99%

“…The relative pharmacological availability of insulin was found to be nearly 98%. Leuprolide acetate was also made into a dissolvable microneedle system using chondroitin sulfate as the polymer matrix [11]. However, low bioavailability was reported due to d egradation of leuprolide in the skin tissue.…”

Section: Dissolving Microneedlesmentioning

confidence: 99%

“…Second, low bioavailability can also be a challenge. Proteolytic enzymes in the skin, though present in lower amounts compared with other routes, might cause drug degradation as seen in one of the studies with leuprolide [11]. Another very important aspect to be considered is protein stability during the fabrication process and product storage.…”

Section: Sustained Release By Skin Pretreatment With Microneedlesmentioning

confidence: 99%

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Transdermal Delivery of biopharmaceuticals: Dream or reality?

Katikaneni

2015

Ther. Deliv.

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The skin being the largest organ of the body presents a potential route for administration of drugs. Passive transdermal products such as gels, creams and patches deliver drugs effectively across the skin. However, this approach is limited to lipophilic molecules with low molecular weights. Passive transdermal delivery of proteins and peptides which are hydrophilic with high molecular weights is negligible. This led to the development of various ways of surmounting the skin barrier so as to make this route feasible for peptide and protein delivery. The current article reviews various active transdermal technologies with special emphasis on microneedle mediated delivery. Microneedles, especially dissolvable microneedles present an excellent platform for protein and peptide delivery. Significant advances have been made in the past decade in this area. Published literature shows a broad spectrum of molecules being delivered successfully via microneedles. However, success in clinic will give a boost to all the efforts and advances made in this field so far.

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“…The drug was formulated at the acral portion of the DMs, which was inserted into the region of the epidermis and/or epidermal/dermal junctions by pressing with fingers. Two-layered DMs were applied to not only biopharmaceuticals but also hydrophilic low molecular weight (MW) drugs, desmopressin, 20) leuprolide, 21) and sumatriptan 22) where high BAs, 84.2-95.1%, were obtained. However, the formulated amount of drug in DMs was limited to be 1.0 mg at most.…”

mentioning

confidence: 99%

Method to Increase the Systemically Delivered Amount of Drug from Dissolving Microneedles

Ito

Hamasaki

Higashino

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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To increase the absorbed amount of a drug from dissolving microneedles (DMs), three DM array chips were prepared in which (1) the drug was localized at the acral portion of DMs, (2) the drug was loaded in each whole DM, and (3) the drug was loaded in DMs and the chip. Fluorescein free form (FL) and its sodium salt (FLNa) were used as model drugs. The DM array chip had 15-mm diameter with 225 DMs, each 500-µm long with a 300-µm diameter base. The respective FLNa contents in the three chips were (1) Key words systemic delivery; dissolving microneedle; percutaneous absorption; rat Transdermal drug delivery systems (TDDS) are attractive drug delivery systems (DDS) for the systemic delivery of drugs with high safety. 1) However, TDDS products of drugs are only nine compounds such as nicotine, fentanyl, and hormones. The main reason is the poor permeability of drugs through the human skin. Moreover, most drugs do not permeate through the skin at therapeutically relevant rates. Consequently, a therapeutic drug concentration is not maintained in systemic circulation. To increase the permeability of the drug through the skin, several methods such as chemical enhancers, electric fields, ultrasound, and thermal methods have been attempted.2-6) Nevertheless, those technologies have not been applied to drugs as TDDS, because they often show skinrelated side-effects, skin damage, etc. To overcome the limitations of those technologies, microneedles (MNs) are being studied 7) : small needles by which microconduits are formed on the skin surface and through which drugs are absorbed into the skin. Human skin comprises three layers. The outermost one is the stratum corneum that is dead tissue with thickness of 10-15 µm. The stratum corneum has a strong primary barrier function against exogenous compounds, including drugs. MNs physically destroy the stratum corneum. Consequently, the drug permeates through the skin. MNs do not cause pain. Now, MNs of four kinds are used [8][9][10] : (1) extremely small needles through which the drug solution can be injected into the skin; (2) metallic and/or silastic MNs onto which surface drug is coated; (3) metallic and/or silastic MNs by which microconduits are made on the skin, after which a drug solution or cream is applied following removal of the microneedle; and (4) dissolving microneedles (DMs).11) DMs are made of watersoluble biopolymers such as chondroitin sulfate, hyaluronic acid and dextran, in which drug molecules are formulated as a solid dispersion or suspension.12) An important advantage of DMs over other MNs is that DMs have high biocompatibility, because the base polymer is made of water-soluble biopolymers and is more compatible with the human body than metal and silastic MNs. We have been studying on DMs for use as a delivery system for hydrophilic drugs such as peptide protein drugs. Results of those studies have improved the bioavailability (BA) of macromolecular drugs having poor permeability through the skin, for example 91.3-97.7% for insulin in mice 13) and of 81.5-102.3...

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Incidence of low bioavailability of leuprolide acetate after percutaneous administration to rats by dissolving microneedles

Cited by 52 publications

References 40 publications

Microneedles for drug and vaccine delivery

Microneedles for drug and vaccine delivery

Transdermal Delivery of biopharmaceuticals: Dream or reality?

Method to Increase the Systemically Delivered Amount of Drug from Dissolving Microneedles

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