Swellable microneedles based transdermal drug delivery: Mathematical model development and numerical experiments

Recently, swellable microneedles (SMNs) have gained significant interest due to their potential applications in transdermal drug delivery (TDD). SMNs swell by absorbing interstitial fluid in the skin, and they facilitate drug transport into the skin without polymer dissolution. To establish the SMNs for practical usages, one requires an accurate understanding of the drug transport mechanisms from these MNs that would allow both controlled TDD as well as optimisation of the MN geometries. In addressing this issue, a mathematical model is formulated which incorporates the key parameters defining the skin properties and physicochemical properties of the MNs, such as the polymer swelling capacity, mechanical deformation, amount of drug loading, and penetration depth in the skin. Numerical simulations are performed using well-defined MN parameters which represent the MN constituent and drug, namely, polyvinyl alcohol and insulin, in this study. The proposed mathematical model predicts that insulin diffuses into the blood to reach a maximum concentration of 11.72 ng/ml in 1.5 h, and ~95% insulin is eliminated from the blood within 11 h. The rate of insulin diffusion to blood increases with an increase in MN swelling. However, not much difference is observed in the insulin profiles when MNs swell more than two times their mass as the skin tends to displace the MN out of the skin, as it increases the length of the diffusion pathway for the drug in the skin layers. The depth of MN penetration affects the overall insulin delivery, with insulin getting eliminated from the body in 8 h when MN is fully inserted into the skin. The rate of change of blood concentration of insulin is found to increase and decrease non-linearly with time for the cases studied in this paper. The developed model provides a platform for optimization of SMNs for the controlled delivery of different drug molecules.