Polymer Microneedles for Controlled-Release Drug Delivery
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
As an alternative to hypodermic injection or implantation of controlled-release systems, this study designed and evaluated biodegradable polymer microneedles that encapsulate drug for controlled release in skin and are suitable for self-administration by patients.
Arrays of microneedles were fabricated out of poly-lactide-co-glycolide using a mold-based technique to encapsulate model drugs—calcein and bovine serum albumin (BSA)—either as a single encapsulation within the needle matrix or as a double encapsulation, by first encapsulating the drug within carboxymethylcellulose or poly-l-lactide microparticles and then encapsulating drug-loaded microparticles within needles.
By measuring failure force over a range of conditions, poly-lactide-co-glycolide microneedles were shown to exhibit sufficient mechanical strength to insert into human skin. Microneedles were also shown to encapsulate drug at mass fractions up to 10% and to release encapsulated compounds within human cadaver skin. In vitro release of calcein and BSA from three different encapsulation formulations was measured over time and was shown to be controlled by the encapsulation method to achieve release kinetics ranging from hours to months. Release was modeled using the Higuchi equation with good agreement (r 2 ≥ 0.90). After microneedle fabrication at elevated temperature, up to 90% of encapsulated BSA remained in its native state, as determined by measuring effects on primary, secondary, and tertiary protein structure.
Biodegradable polymer microneedles can encapsulate drug to provide controlled-release delivery in skin for hours to months.
- Langer, R. (1998) Drug delivery and targeting. Nature 392: pp. 5-10
- Rosen, H., Abribat, T. (2005) The rise and rise of drug delivery. Nat. Rev. Drug Discov. 4: pp. 381-385 CrossRef
- Periti, P., Mazzei, T., Mini, E. (2002) Clinical pharmacokinetics of depot leuprorelin. Clin. Pharmacokinet. 41: pp. 485-504 CrossRef
- Brem, H., Piantadosi, S., Burger, P. C., Walker, M., Selker, R., Vick, N. A., Black, K., Sisti, M., Brem, S., Mohr, G. (1995) Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-Brain Tumor Treatment Group. Lancet 345: pp. 1008-1012 CrossRef
- Kaushik, S., Hord, A. H., Denson, D. D., McAllister, D. V., Smitra, S., Allen, M. G., Prausnitz, M. R. (2001) Lack of pain associated with microfabricated microneedles. Anesth. Analg. 92: pp. 502-504 CrossRef
- Mikszta, J. A., Alarcon, J. B., Brittingham, J. M., Sutter, D. E., Pettis, R. J., Harvey, N. G. (2002) Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nat. Med. 8: pp. 415-419 CrossRef
- Henry, S., McAllister, D., Allen, M. G., Prausnitz, M. R. (1998) Microfabricated microneedles: a novel method to increase transdermal drug delivery. J. Pharm. Sci. 87: pp. 922-925 CrossRef
- Cormier, M., Johnson, B., Ameri, M., Nyam, K., Libiran, L., Zhang, D. D., Daddona, P. (2004) Transdermal delivery of desmopressin using a coated microneedle array patch system. J. Control. Release 97: pp. 503-511
- Miyano, T., Tobinaga, Y., Kanno, T., Matsuzaki, Y., Takeda, H., Wakui, M., Hanada, K. (2005) Sugar micro needles as transdermic drug delivery system. Biomed. Microdevices 7: pp. 185-188 CrossRef
- Prausnitz, M. R. (2004) Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev. 56: pp. 581-587 CrossRef
- Prausnitz, M., Mikszta, J., Raeder-Devens, J. Microneedles. In: Smith, E., Maibach, H. eds. (2005) Percutaneous Penetration Enhancers. CRC, Boca Raton, FL, pp. 239-255
- Gardeniers, J. G. E., Luttge, R., Berenschot, J. W., Boer, M. J., Yeshurun, Y., Hefetz, M., Oever, R., Berg, A. (2003) Silicon micromachined hollow microneedles for transdermal liquid transport. J. MEMS 6: pp. 855-862
- McAllister, D. V., Wang, P. M., Davis, S. P., Park, J.-H., Canatella, P. J., Allen, M. G., Prausnitz, M. R. (2003) Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc. Natl. Acad. Sci. USA 100: pp. 13755-13760 CrossRef
- Sivamani, R. K., Stoeber, B., Wu, G. C., Zhai, H., Liepmann, D., Maibach, H. (2005) Clinical microneedle injection of methyl nicotinate: stratum corneum penetration. Skin Res. Technol. 11: pp. 152-156 CrossRef
- J. H. Park, S. P. Davis, Y. K. Yoon, M. R. Prausnitz, and M. G. Allen. Micromachined biodegradable microstructures. In The 16th Annual International Conference on Micro Electro Mechanical Systems, IEEE, Piscataway, NJ, 2003, pp. 371–374.
- Davis, S. P., Landis, B. J., Adams, Z. H., Allen, M. G., Prausnitz, M. R. (2004) Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. J. Biomech. 37: pp. 1155-1163 CrossRef
- Saltzman, W. M. (2001) Drug Delivery: Engineering Principles for Drug Therapy. Oxford University Press, New York
- Kanjickal, D. G., Lopina, S. T. (2004) Modeling of drug release from polymeric delivery systems—a review. Crit. Rev. Ther. Drug Carr. Syst. 21: pp. 345-386 CrossRef
- Madou, M. J. (2002) Fundamentals of Microfabrication: The Science of Miniaturization. CRC, Boca Raton, FL
- Park, J.-H., Allen, M. G., Prausnitz, M. R. (2005) Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J. Control. Release 104: pp. 51-66 CrossRef
- Lee, H. K., Park, J. H., Kwon, K. C. (1997) Double-walled microparticles for single shot vaccine. J. Control. Release 44: pp. 283-293 CrossRef
- Benoit, J.-P., Marchais, H., Rolland, H., Velde, V. V. Biodegradable microspheres: advances in production technology. In: Benita, S. eds. (1996) Microencapsulation. Marcel Dekker, New York, pp. 35-72
- Gupta, R. K., Chang, A. C., Griffin, P., Rivera, R., Guo, Y. Y., Siber, G. R. (1997) Determination of protein loading in biodegradable polymer microspheres containing tetanus toxoid. Vaccine 15: pp. 672-678 CrossRef
- Y. W. Chien (ed.), Novel Drug Delivery Systems: Fundamentals, Developmental Concepts, Biomedical Assessments, Marcel Dekker, New York, 1991.
- Baker, R. W., Lonsdale, H. K. Controlled release: mechanisms and rates. In: Tanquary, A. C., Lacey, R. E. eds. (1974) Controlled Release of Biologically Active Agents. Advances in Experimental Medicine and Biology, Vol. 47. Plenum, New York, pp. 15-72
- Faisant, N., Siepmann, J., Benoit, J. P. (2002) PLGA-based microparticles: elucidation of mechanisms and a new, simple mathematical model quantifying drug release. Eur. J. Pharm. Sci. 15: pp. 355-366 CrossRef
- Bulone, D., Martorana, V., Biagio, P. L. (2001) Effects of intermediates on aggregation of native bovine serum albumin. Biophys. Chem. 91: pp. 61-69 CrossRef
- Liu, W. R., Langer, R., Klibanov, A. M. (1991) Moisture-induced aggregation of lyophilized proteins in the solid state. Biotechnol. Bioeng. 37: pp. 177-184 CrossRef
- Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: pp. 265-275
- Berne, B. J., Pecora, R. (2000) Dynamic Light Scattering: With Applications to Chemistry, Biology, and Physics. Dover Publications, Mineola, NY
- G. D. Fasman (ed.). Circular Dichroism and the Conformational Analysis of Biomolecules. Plenum, New York, 1996.
- Lu, L., Garcia, C. A., Mikos, A. G. (1999) In vitro degradation of thin poly(DL-lactic-co-glycolic acid) films. J. Biomed. Mater. Res. 46: pp. 236-244 CrossRef
- K. Park (ed.), Controlled Drug Delivery: Challenges and Strategies. American Chemical Society, Washington, DC, 1997.
- Monteiro-Riviere, N. A. Comparative anatomy, physiology, and biochemistry of mammalian skin. In: Hobson, D. W. eds. (1991) Dermal and Ocular Toxicology. CRC, Boca Raton, FL, pp. 3-71
- Rousche, P. J., Normann, R. A. (1992) A method for pneumatically inserting an array of penetrating electrodes into cortical tissue. Ann. Biomed. Eng. 20: pp. 413-422 CrossRef
- Yang, M., Zahn, J. D. (2004) Microneedle insertion force reduction using vibratory actuation. Biomed. Microdevices 6: pp. 177-182 CrossRef
- Arakawa, T., Prestrelski, S. J., Kenney, W. C., Carpenter, J. F. (2001) Factors affecting short-term and long-term stabilities of proteins. Adv. Drug Deliv. Rev. 46: pp. 307-326 CrossRef
- Prausnitz, M. R., Mitragotri, S., Langer, R. (2004) Current status and future potential of transdermal drug delivery. Nat. Rev. Drug Discov. 3: pp. 115-124 CrossRef
- Physicians' Desk Reference. Thomson PDR, Montvale, NJ, 2005.
- Mitragotri, S. (2005) Immunization without needles. Nat. Rev. Immunol. 5: pp. 905-916 CrossRef
- Polymer Microneedles for Controlled-Release Drug Delivery
Volume 23, Issue 5 , pp 1008-1019
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- controlled-release drug delivery
- protein stability
- transdermal drug delivery
- Industry Sectors
- Author Affiliations
- 1. Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA
- 2. School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA
- 3. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA