Optimization of targeted drug delivery from systems of microneedles

1Lyashko, SI, Klyushin, DA, Onotskyi, VV, Bondar, OS
1Taras Shevchenko National University of Kyiv
Dopov. Nac. akad. nauk Ukr. 2017, 11:16-23
Section: Information Science and Cybernetics
Language: Ukrainian

We consider the simulation and optimization problem of transdermal drug transport from systems of solvable microneedles. We solve a one-dimensional problem of vertical transport of drugs through the porous media with point sources simulating solvable microneedles. Controlling the intensity and setting coordinates of the sources, we solved the problem of optimal control over the transdermal drug transport and achieved a desired distribution of drugs in epidermis with acceptable precision. To solve the boundary-initial problems, we use finite-difference methods and two-step symmetrizable algorithm.

Keywords: difference scheme, microneedle system, optimization, point source, simulation, transdermal diffusion
  1. Kaushik, S., Hord, A. H. & Denson, D. D. (2001). Lack of pain associated with microfabricated microneedles. Anesth. Analg., 92, pp. 502-504. https://doi.org/10.1213/00000539-200102000-00041
  2. Sivamani, R. K., Stoeber, B. & Wu, G. C. (2005). Clinical microneedle injection of methylnicotinate: stratum corneum penetration. Skin Res. Tech. 11, No. 11, pp. 152-156. https://doi.org/10.1111/j.1600-0846.2005.00107.x
  3. 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. https://doi.org/10.1038/nrd1304
  4. Lee, J. W., Choi, S.-O., Felner, E. I. & Prausnitz, M. R. (2001). Dissolving microneedle patch for transdermal delivery of human growth hormone. Small., 7, pp. 531-539. https://doi.org/10.1002/smll.201001091
  5. Sullivan, S. P., Murthy, N. & Prausnitz, M. R. (2008). Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv Mater., 20, pp. 933-938. https://doi.org/10.1002/adma.200701205
  6. Lahiji, S. F., Dangol, M. & Jung, H. (2015). A patchless dissolving microneedle delivery system enabling rapid and efficient transdermal drug delivery. Scientific Reports. 5. Article number: 7914. doi: https://doi.org/10.1038/srep07914. Available at http://www.nature.com/articles/srep07914
  7. Ita, K. (2015). Transdermal Delivery of Drugs with Microneedles — Potential and Challenges. Pharmaceutics. 7, No. 3, pp. 90-105. https://doi.org/10.3390/pharmaceutics7030090
  8. Kalia, Y. N. & Guy, R. H. (2001). Modeling transdermal drug release. Adv. Drug Deliv. Rev., 48, pp. 159-172. https://doi.org/10.1016/S0169-409X(01)00113-2
  9. Rim, J. E., Pinsky, P. M. & van Osdol, W. W. (2005). Finite element modeling of coupled diffusion with par titioning in transdermal drug delivery. Ann. Biomed. Eng., 2005. 33, pp. 1422-1438. https://doi.org/10.1007/s10439-005-5788-6
  10. Al-Qallaf, B., Das, D. B., Mori, D. & Cui, Z. (2007). Modelling transdermal delivery of high molecular weight drugs from microneedle systems. Phil. Trans. R. Soc. A, 365, pp. 2951-2967. https://doi.org/10.1098/rsta.2007.0003
  11. Al-Qallaf, B. & Das, D. B. (2008). Optimization of square microneedle arrays for increasing drug permeability in skin. Chem. Eng. Sci., 63, No. 9, pp. 2523-2535. https://doi.org/10.1016/j.ces.2008.02.007
  12. Powell, A. (2007). Optimizing Transdermal Drug Delivery Through Diffusion Modeling. Control Release Society Newsletter, 24, No. 4, pp. 17-19.
  13. Olatunji, O., Das, D. B. & Nassehi, V. (2012). Modelling transdermal drug delivery using microneedles: Effect of geometry on drug transport behaviour. J. Pharm. Sci. 101, No. 1, pp. 164-175. https://doi.org/10.1002/jps.22736
  14. Lyashko, S.I. (2002) Generalized Optimal Control of Linear Systems with Distributed Parameters. Kluwer.
  15. Lyashko, I. I., Gryschenko, O. Yu., Sklepovy, V. M. & Onotskyi ,V. V. (2003) Economical numerical algorithms for some class of non-linear boundary problems. Dopov. Nac. akad. nauk Ukr., No. 3, pp. 68-72.