Application of Microneedle Arrays for Enhancement of Transdermal Permeation of Insulin: In Vitro Experiments, Scaling Analyses and Numerical Simulations

Abstract

Abstract. The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses were done using dimensionless parameters like concentration of drug (C t /C s ), thickness (h/L) and surface area of the skin (S a /L 2 ). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN-treated skin and experimental parameters like passive diffusion coefficient. A 1.6-fold increase in transdermal flux and 1.9-fold decrease in lag time values were observed with 1.5 mm MN when compared with passive studies. Good correlation (R 2 >0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f 2 ≥50). Insulin permeation significantly increased with increase in donor concentration and MN length (p<0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans.

Microneedle-assisted transdermal delivery of Zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations

“…The scaling analyses were carried out based on the principles of the Buckingham π theorem where it is defined that the dimensionless concentration of a drug, which permeates through skin, can be defined in terms of key nondimensional parameters (e.g., MN lengths) using the procedures described in previous papers 13,19 .…”

“…The MATLAB programme was use to process the histological sections images of skin treated with MNs and these processed images were further coupled with the experimental permeation parameter, e.g., passive diffusion coefficient and imported into COMSOL simulator software 13,20 .…”

“…Using scaling analyses, correlations were developed between the dimensionless parameters, namely, the amount of ZMT permeated (C t /C s ) and skin thickness (h/L) and surface area of skin (S a /Lparameters of MN, like length (L), on overall permeation enhancement by MNs of same design (ADM) (Fig 9A, B ,respectively) 13,19 . Eqs.…”

Effect of microneedles on transdermal permeation enhancement of amlodipine

“…The scaling analyses were carried out based on the principles of the Buckingham π theorem where it is defined that the dimensionless concentration of a drug, which permeates through skin, can be defined in terms of key nondimensional parameters (e.g., MN lengths) using the procedures described in previous papers [21,22].…”

“…Moreover, the obtained AMLO permeation data was subjected to mathematical treatment using scaling analyses to obtain correlations between dimensionless parameters like amount of AMLO permeated (C t /C s ) and various variables of the study like surface area (Sa/L 2 ) and thickness (h/L) of skin based on the principles of Buckingham π theorem as described in a previous papers in order to gain insights into the phenomenon of AMLO transport behaviour and distribution in the skin layers [21,22]. …”