Development and Characterization of Gantrez^® S-97 and Hyaluronic Acid Microneedles for Transdermal Fluorescein Sodium Delivery

Abstract:

Microneedles (MNs) are attractive micron scale technology, which has been used as a physical force to create transport pathways and enhance the permeability of drugs into the skin. Fluorescein sodium (FS), a hydrophilic drug was loaded in MNs for transportation through skin. The purposes of this study were to develop and evaluate the optimal formulation of FS-loaded polymeric microneedles (MNs) as a device for transdermal drug delivery system. The FS-MNs were fabricated by micro-molding technique and prepared by using Gantrez^® S-97 (G) and hyaluronic acid (HA). The physical appearances were observed under digital microscope. The mechanical properties were determined by a texture analyzer. The insertion study was tested on neonatal porcine skin. The MNs height changing after insertion into the skin at predetermined times was measured to show dissolution ability of MNs. Finally, the drug permeation profile of FS-MNs was investigated by Franz diffusion cell. For the results, all formulations were complete fabrication of conical microneedle array (11 rows x 11 columns in 10 mm² patch area) with average 600 + 20 μm in height, 300 + 5 μm in width, and 600 + 10 μm in interspace. The percent decrease of MNs height in mechanical strength of 30%G+5%HA was significantly less than others at 1.8 to 8.8 N/121 array. The formulation mixing with 30% Gantrez^® S-97 had 100% of penetration into porcine skin. The dissolution ability showed that MNs were completely dissolved within 60 minutes. At 24 h of skin permeation, the FS permeated through the skin from 1%FS solution, 30%G+1%FS MNs, and 30%G+5%HA+1%FS MNs was 1.00%, 4.27% and 7.53%, respectively. The flux values of 1%FS solution, 30%G+1%FS MNs, and 30%G+5%HA+1%FS MNs were 0.006 μg/cm²/min, 0.032 μg/cm²/min, and 0.037 μg/cm²/min, respectively, indicating the highest skin permeability of FS from 30%G+5%HA+1%FS MNs. In conclusion, the 30%G+5%HA+1%FS formulation presented appropriate MNs properties as a device for transdermal drug delivery system.

• Periodical: Key Engineering Materials (Volume 859)
• Pages: 125-131
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.859.125
• Online since: August 2020
• Authors: Phuvamin Suriyaamporn, Worranan Rangsimawong, Praneet Opanasopit, Tanasait Ngawhirunpat*
• Keywords: Fluorescein Sodium, Gantrez^® S-97, Hyaluronic Acid, Microneedle, Transdermal Drug Delivery

References

[1] S. Al-Zahrani, M. Zaric, C. McCrudden, C. Scott, A. Kissenpfennig, R.F. Donnelly, Microneedle-mediated vaccine delivery: harnessing cutaneous immunobiology to improve efficacy, Expert Opinion on Drug Delivery. 9 (2012) 541-550.

DOI: 10.1517/17425247.2012.676038

[2] A. Mero, M. Campisi, Hyaluronic acid bioconjugates for the delivery of bioactive molecules, Polymers. 6 (2014) 346-369.

DOI: 10.3390/polym6020346

[3] Y. Hiraishi, T. Nakagawa, Y.S. Quan, F. Kamiyama, S. Hirobe, N. Okada, S. Nakagawa, Performance and characteristics evaluation of a sodium hyaluronate-based microneedle patch for a transcutaneous drug delivery system, International Journal of Pharmaceutics. 441, 1-2 (2013) 570-579.

DOI: 10.1016/j.ijpharm.2012.10.042

[4] E. Larraneta, J. Moore, E.M. Vicente-Perez, P. Gonzalez-Vazquez, R. Lutton, A.D. Woolfson, et al., A proposed model membrane and test method for microneedle insertion studies, International Journal of Pharmaceutics. 472, 1-2 (2014) 65-73.

DOI: 10.1016/j.ijpharm.2014.05.042

[5] K.M. El-Say, Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper-Lin small composite design, Drug Design, Development and Therapy. 10, (2016) 825-839.

DOI: 10.2147/dddt.s101900

[6] J.W. Lee, J.H. Park, M.R. Prausnitz, Dissolving microneedles for transdermal drug delivery, Biomaterials. 29, 13 (2008) 2113-2124.

DOI: 10.1016/j.biomaterials.2007.12.048

[7] E. Larrañeta, M. Henry, N.J. Irwin, J. Trotter, A.A. Perminova, R.F. Donnelly, Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications, Carbohydrate Polymers. 181 (2018) 1194–1205.

DOI: 10.1016/j.carbpol.2017.12.015

[8] G.A. Simon, H.I. Maibach, The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations-an overview, Skin Pharmacology and Applied Skin Physiology. 13, 5 (2000) 229-234.

DOI: 10.1159/000029928