Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays

Martin J. Garland, Katarzyna Migalska, Tuan Mazlelaa Tuan Mahmood, Thakur Raghu Raj Singh, Rita Majithija, Ester Caffarel-Salvador, Cian M. McCrudden, Helen O. McCarthy, A. David Woolfson, Ryan F. Donnelly

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 24 h 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 24 h 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.

Original languageEnglish
Pages (from-to)80-89
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume434
Issue number1-2
DOIs
Publication statusPublished - 15 Sep 2012

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Skin
Pharmaceutical Preparations
Methylene Blue
Membranes
Swine
Equipment and Supplies
In Vitro Techniques

Keywords

  • In vitro release
  • Microneedles
  • Skin model
  • Transdermal drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Garland, M. J., Migalska, K., Tuan Mahmood, T. M., Raghu Raj Singh, T., Majithija, R., Caffarel-Salvador, E., ... Donnelly, R. F. (2012). Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays. International Journal of Pharmaceutics, 434(1-2), 80-89. https://doi.org/10.1016/j.ijpharm.2012.05.069

Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays. / Garland, Martin J.; Migalska, Katarzyna; Tuan Mahmood, Tuan Mazlelaa; Raghu Raj Singh, Thakur; Majithija, Rita; Caffarel-Salvador, Ester; McCrudden, Cian M.; McCarthy, Helen O.; David Woolfson, A.; Donnelly, Ryan F.

In: International Journal of Pharmaceutics, Vol. 434, No. 1-2, 15.09.2012, p. 80-89.

Research output: Contribution to journalArticle

Garland, MJ, Migalska, K, Tuan Mahmood, TM, Raghu Raj Singh, T, Majithija, R, Caffarel-Salvador, E, McCrudden, CM, McCarthy, HO, David Woolfson, A & Donnelly, RF 2012, 'Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays', International Journal of Pharmaceutics, vol. 434, no. 1-2, pp. 80-89. https://doi.org/10.1016/j.ijpharm.2012.05.069
Garland, Martin J. ; Migalska, Katarzyna ; Tuan Mahmood, Tuan Mazlelaa ; Raghu Raj Singh, Thakur ; Majithija, Rita ; Caffarel-Salvador, Ester ; McCrudden, Cian M. ; McCarthy, Helen O. ; David Woolfson, A. ; Donnelly, Ryan F. / Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays. In: International Journal of Pharmaceutics. 2012 ; Vol. 434, No. 1-2. pp. 80-89.
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abstract = "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{\circledR} 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{\circledR} was used as the model membrane, the cumulative percentage permeation of methylene blue 24 h 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 24 h 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.",
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