Delivery of Methotrexate and Characterization of Skin Treated
by Fabricated PLGA Microneedles and Fractional Ablative Laser
Hiep X. Nguyen
Ajay K. Banga
Received: 29 November 2017 /Accepted: 12 February 2018
Springer Science+Business Media, LLC, part of Springer Nature 2018
Purpose This study investigated in vitro transdermal delivery
of methotrexate through dermatomed porcine ear and cadav-
er human skin treated with poly (D,L-lactide-co-glycolide) ac-
id microneedles or fractional ablative laser.
Methods PLGA microneedles were fabricated and charac-
terized using scanning electron microscopy and mechanical
assessment techniques. The integrity of treated skin was eval-
uated by rheometer, transepidermal water loss, and skin elec-
trical resistance measurements. Successful skin microporation
was demonstrated by dye binding, histology, pore uniformity,
confocal laser microscopy, and DermaScan studies. In vitro
permeation experiment was performed on Franz diffusion
cells to determine drug delivery into and across the skin.
Results Both physical treatments resulted in a considerable
decrease in skin resistance and an increase in transepidermal
water loss value. The laser-created microchannels were signif-
icantly larger than those formed by microneedles (p <0.05).
An effective force of 41.04 ± 18.33 N was required to achieve
100% penetration efficiency of the microneedles. For both
porcine ear and human skin, laser ablation provided a signif-
icantly higher methotrexate permeability into the receptor
chamber and skin layers compared to microneedle poration
and untreated skin (p <0.05).
Conclusions Both fractional ablative laser and polymeric
microneedles markedly enhanced in vitro transdermal delivery
of methotrexate into and across skin.
fractional ablative laser
polymeric biodegradable microneedles
FTIR Fourier transform infrared spectrophotometer
PBS Phosphate buffered saline
PLGA Poly Lactic-co-Glycolic Acid
PPI Pore permeability index
RP-HPLC Reversed-phase high performance liquid
SD Standard deviation
SEM Scanning electron microscopy
TEWL Transepidermal water loss
Transdermal drug administration offers considerable advan-
tages over other conventional routes, such as oral or parenter-
al. These include patient compliance, circumvention of hepat-
ic first-pass metabolism, drug degradation in the gastrointes-
tinal tract, and frequent parenteral painful dosing (1).
However, stratum corneum layer of skin prevents most of
therapeutic agents from passively diffusing into the skin, with
the exception of some potent, small, and moderately lipophilic
compounds (2). Several investigators have explored the dis-
ruption to this barrier using different physical enhancement
techniques such as microneedles, thermal, radiofrequency ab-
lation, and laser ablation (3).
Micron-size needles or microneedles can be designed to be
sharp enough to pierce the stratum corneum layer, long
enough to reach the target site, yet short enough to avoid
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11095-018-2369-6) contains supplementary
material, which is available to authorized users.
* Ajay K. Banga
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer
University, Atlanta, GA 30341, USA
Pharm Res (2018) 35:68