Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs.

Dissolving microneedle patches offer promise as a simple, minimally invasive method of drug and vaccine delivery to the skin that avoids the need for hypodermic needles. However, it can be difficult to control the amount and localization of drug within microneedles. In this study, we developed novel microneedle designs to improve control of drug encapsulation and delivery using dissolving microneedles by (i) localizing drug in the microneedle tip, (ii) increasing the amount of drug loaded in microneedles while minimizing wastage, and (iii) inserting microneedles more fully into the skin. Localization of our model drug, sulforhodamine B in the microneedle tip by either casting a highly concentrated polymer solution as the needle matrix or incorporating an air bubble at the base of the microneedle achieved approximately 80% delivery within 10 min compared to 20% delivery achieved by the microneedles encapsulating nonlocalized drug. As another approach, a pedestal was introduced to elevate each microneedle for more complete insertion into the skin and to increase its drug loading capacity by threefold from 0.018 to 0.053 microL per needle. Altogether, these novel microneedle designs provide a new set of tools to fabricate dissolving polymer microneedles with improved control over drug encapsulation, loading, and delivery.

[1]  Takaya Miyano,et al.  Sugar Micro Needles as Transdermic Drug Delivery System , 2005, Biomedical microdevices.

[2]  G. Glenn,et al.  Transcutaneous immunization and immunostimulant strategies: capitalizing on the immunocompetence of the skin , 2003, Expert review of vaccines.

[3]  Mark R Prausnitz,et al.  Microneedles permit transdermal delivery of a skin-impermeant medication to humans , 2008, Proceedings of the National Academy of Sciences.

[4]  J. Bouwstra,et al.  Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[5]  Samir Mitragotri,et al.  Design principles of chemical penetration enhancers for transdermal drug delivery. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Allen,et al.  3-D PATTERNED MICROSTRUCTURES USING INCLINED UV EXPOSURE AND METAL TRANSFER MICROMOLDING , 2006 .

[7]  M. Cormier,et al.  Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. , 2006, Vaccine.

[8]  Mark R. Prausnitz,et al.  Effect of Microneedle Design on Pain in Human Volunteers , 2008, The Clinical journal of pain.

[9]  Adrian C. Williams,et al.  Penetration enhancers. , 2004, Advanced drug delivery reviews.

[10]  Jung-Hwan Park,et al.  Dissolving microneedles for transdermal drug delivery. , 2008, Biomaterials.

[11]  M. Prausnitz,et al.  Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge , 2009, Proceedings of the National Academy of Sciences.

[12]  A. Fadda,et al.  Vesicular carriers for dermal drug delivery , 2009, Expert opinion on drug delivery.

[13]  M. Prausnitz,et al.  Microneedles for Drug Delivery , 2008 .

[14]  Chandra Sekhar Kolli,et al.  Characterization of Solid Maltose Microneedles and their Use for Transdermal Delivery , 2007, Pharmaceutical Research.

[15]  W. Koff,et al.  A Dose-Ranging Study of a Prototype Synthetic HIV-1MN V3 Branched Peptide Vaccine , 1996 .

[16]  J. Yoshimitsu,et al.  Self-dissolving microneedles for the percutaneous absorption of EPO in mice , 2006, Journal of drug targeting.

[17]  Mark R Prausnitz,et al.  Coated microneedles for transdermal delivery. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[18]  Mahmoud Ameri,et al.  Transdermal delivery of desmopressin using a coated microneedle array patch system. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[19]  Robert Langer,et al.  Transdermal drug delivery , 2008, Nature Biotechnology.

[20]  D. Barrow,et al.  Microfabricated silicon microneedles for nonviral cutaneous gene delivery , 2004, The British journal of dermatology.

[21]  R. Couch,et al.  Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons. , 2006, Archives of internal medicine.

[22]  Samir Mitragotri,et al.  Micro-scale devices for transdermal drug delivery. , 2008, International journal of pharmaceutics.

[23]  Jung-Hwan Park,et al.  Tapered Conical Polymer Microneedles Fabricated Using an Integrated Lens Technique for Transdermal Drug Delivery , 2007, IEEE Transactions on Biomedical Engineering.

[24]  Adam J. Davidson,et al.  Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability , 2008 .

[25]  W. Koff,et al.  A dose-ranging study of a prototype synthetic HIV-1MN V3 branched peptide vaccine. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. , 1996, The Journal of infectious diseases.

[26]  C. Alving,et al.  Transcutaneous immunization: A human vaccine delivery strategy using a patch , 2000, Nature Medicine.

[27]  Dorian Liepmann,et al.  Microneedles and transdermal applications , 2007, Expert opinion on drug delivery.

[28]  Wijaya Martanto,et al.  Mechanism of fluid infusion during microneedle insertion and retraction. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[29]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[30]  Vincent J. Sullivan,et al.  Microneedle-Based Intradermal Delivery of the Anthrax Recombinant Protective Antigen Vaccine , 2006, Infection and Immunity.

[31]  Regina Luttge,et al.  Silicon micromachined hollow microneedles for transdermal liquid transport , 2003 .

[32]  Mark R Prausnitz,et al.  Minimally Invasive Protein Delivery with Rapidly Dissolving Polymer Microneedles , 2008, Advanced materials.

[33]  Mark R Prausnitz,et al.  Microneedles for transdermal drug delivery. , 2004, Advanced drug delivery reviews.