Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays.
A plethora of studies have described the in vitro assessment of dissolving microneedle (MN) arrays for enhanced transdermal drug delivery, utilising a wide variety of model membranes as a representation of the skin barrier. However, to date, no discussion has taken place with regard to the choice of model skin membrane and the impact this may have on the evaluation of MN performance. In this study, we have, for the first time, critically assessed the most common types of in vitro skin permeation models - a synthetic hydrophobic membrane (Silescol(®) of 75 μm) and neonatal porcine skin of definable thickness (300-350 μm and 700-750 μm) - for evaluating the performance of drug loaded dissolving poly (methyl vinyl ether co maleic acid) (PMVE/MA) MN arrays. It was found that the choice of in vitro skin model had a significant effect on the permeation of a wide range of small hydrophilic molecules released from dissolving MNs. For example, when Silescol(®) was used as the model membrane, the cumulative percentage permeation of methylene blue 24h after the application of dissolvable MNs was found to be only approximately 3.7% of the total methylene blue loaded into the MN device. In comparison, when dermatomed and full thickness neonatal porcine skin were used as a skin model, approximately 67.4% and 47.5% of methylene blue loaded into the MN device was delivered across the skin 24h after the application of MN arrays, respectively. The application of methylene blue loaded MN arrays in a rat model in vivo revealed that the extent of MN-mediated percutaneous delivery achieved was most similar to that predicted from the in vitro investigations employing dermatomed neonatal porcine skin (300-350 μm) as the model skin membrane. On the basis of these results, a wider discussion within the MN community will be necessary to standardise the experimental protocols used for the evaluation and comparison of MN devices.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
Martin J
MJ
Garland
Katarzyna
K
Migalska
Tuan-Mazlelaa
TM
Tuan-Mahmood
Thakur
T
Raghu Raj Singh
Rita
R
Majithija
Ester
E
Caffarel-Salvador
Cian M
CM
McCrudden
Helen O
HO
McCarthy
A
A
David Woolfson
Ryan F
RF
Donnelly
D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008567:Membranes, Artificial; D008751:Methylene Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D008845:Microinjections; D008954:Models, Biological; D009339:Needles; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D013552:Swine; D013997:Time Factors
D008567:Membranes, Artificial; D008751:Methylene Blue