Microneedles-Mediated Transdermal Delivery

The objective of the present study was to evaluate the potential of hollow microneedles for enhancing the transdermal delivery of Bovine Serum Albumin (MW~66,000 Da)-Fluorescein Isothiocyanate (BSA-FITC) conjugate, a hydrophilic large molecular compound. Moreover, the effect of different formulations was evaluated. The series of binary mixtures composed of propylene glycol (PG) and pH 7.4 phosphate buffer solution (PBS) was prepared and used as a medium for BSA-FITC. The results showed that there was no permeation of BSA-FITC solution across the neonatal porcine skin without using hollow microneedles, whereas the cumulative amount of BSA-FITC released at 8 h through the neonatal porcine skin was about 60-70% when using hollow microneedles. Furthermore, the results demonstrated that the higher volume of PG in binary mixtures injected, the lower cumulative amount of BSA-FITC released and release rate of BSA-FITC from skin. These release profiles of BSA-FITC in binary mixtures were expressed by Fick-s law of diffusion. These results suggest the utilization of hollow microneedle to enhance transdermal delivery of protein and provide useful information for designing an effective hollow microneedle system.

Authors:

• M. Petchsangsai
• N. Wonglertnirant
• T. Rojanarata
• P. Opanasopit
• T. Ngawhirunpat

Keywords:

• Hydrophilic macromolecules
• Microneedles
• Propylene glycol
• Transdermal drug delivery

References:

[1] J. Hadgraft, "Skin, the final frontier," Int J Pharm, vol. 224, 2001, pp.
1-18.
[2] A. Naik, K.N. Yogeshvar, and G.H. Richard, "Transdermal drug
delivery: Overcoming the skin-s barrier function," PSTT, vol. 3, 2000,
318-326.
[3] S.N. Murthy, and H.N. Shivakumar, "Topical and transdermal drug
delivery," in Handbook of non-invasive drug delivery systems, 2010,
pp. 1-36.
[4] M. Milewski, and A. L. Stinchcomb, "Vehicle composition influence on
the microneedle-enhanced transdermal flux of naltrexone
hydrochloride," Pharm Res, vol. 28, 2010, pp. 124-134.
[5] H. A. E. Benson, "Transdermal drug delivery: Penetration enhancement
techniques," Current Drug Delivery, vol. 2, 2005, pp. 23-33.
[6] S. Henry, M.V. Devin, A.G. Mark, and P.R. Mark, "Microfabricated
microneedles: A novel approach to transdermal drug delivery," J.
Pharm. Sci., vol. 87, 1998, pp. 922-925.
[7] P.R. Mark, "Microneedles for transdermal drug delivery," Adv. Drug
Del. Rev., vol 56, 2004, pp. 581-587.
[8] B. Bendas, S. Ulrike, and N. Reinhard, "Influence of propylene glycol
as cosolvent on mechanisms of drug transport from hydrogels," Int. J.
Pharm., vol. 116, 1995, pp. 19-30.
[9] P. Karade, and S. Mitragotri, "Enhancement of transdermal drug
delivery via synergistic action of chemicals," Biochim. Biophys. Acta.,
vol 1788, 2009, pp. 2362-2373.
[10] W. Nanthida, H. Todo, O. Preneet, N. Tanasait, and K. Sugibayashi,
"Macromolecular delivery into skin using a hollow microneedle," Biol.
Pharm. Bull., vol. 33, 2010, pp. 1988-1993.
[11] P. Maleenart, W. Nanthida, R. Theerasak, O. Preneet, and N. Tanasait,
"Application of hollow microneedle for transdermal delivery of bovine
serum albumin-florescein isothiocyanate conjugate," Adv. Mat. Res.,
vol. 338, 2011, pp. 365-368.
[12] D.F. Ryan et al., "Optical coherence tomography is a valuable tool in
the study of the effects of microneedle geometry on skin penetration
characteristics and in-skin dissolution," J. Control. Release., vol. 147,
2010, pp. 333-341.
[13] W.Q. Lin et al., "Transdermal delivery of antisense oligonucleotides
with microprojection patch (Macroflux®) technology," Pharm. Res., vol.
18, 2001, pp. 1789-1793.
[14] D.V. McAllister et al., "Microfabricated needles for transdermal
delivery of macromolecules and nanoparticles: Fabrication methods and
transport studies," PNAS, vol. 100, 2003, pp. 13755-13760.
[15] G.S. Harvinder, and P.R. Mark, "Coated microneedles for transdermal
delivery," J. Control. Release., vol. 117, 2007, pp. 227-237.