Abstract
The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen™ 1200, and Admin Pen™ 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle-treated skin. As the needle length increased from 500 to 1100 and 1400 μm, drug delivery increased from 14.50 ± 2.35 to 32.38 ± 3.33 and 74.40 ± 15.86 μg/cm2, respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib.
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Abbreviations
- BCC:
-
Basal cell carcinoma
- TEWL:
-
Transepidermal water loss
- SEM:
-
Scanning electron microscopy
- PBS:
-
Phosphate-buffered saline
- PEG 400:
-
Polyethylene glycol 400
- PG:
-
Propylene glycol
- SD:
-
Standard deviation
- HPLC:
-
High-performance liquid chromatography
- SIT:
-
Skin irritation test
- PPI:
-
Pore permeability index
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Acknowledgments
We are thankful to Ashana Puri, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, for helping us to read the manuscript and provide helpful suggestions.
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The authors do not have any conflicts of interest to report for this manuscript.
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Nguyen, H.X., Banga, A.K. Enhanced skin delivery of vismodegib by microneedle treatment. Drug Deliv. and Transl. Res. 5, 407–423 (2015). https://doi.org/10.1007/s13346-015-0241-3
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DOI: https://doi.org/10.1007/s13346-015-0241-3