Topical delivery of vismodegib using ablative fractional laser and micro-emulsion formulation in vitro.
ablative fractional laser
basal cell carcinoma
drug formulation
emulsion
franz diffusion cell
hedgehog inhibitor
laser-assisted drug delivery
topical drug delivery
vismodegib
Journal
Lasers in surgery and medicine
ISSN: 1096-9101
Titre abrégé: Lasers Surg Med
Pays: United States
ID NLM: 8007168
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
accepted:
31
07
2018
pubmed:
29
8
2018
medline:
22
1
2020
entrez:
29
8
2018
Statut:
ppublish
Résumé
Hedgehog inhibitors such as vismodegib are targeted drugs widely used for the treatment of basal cell carcinomas; however, their use is significantly limited by frequent systemic side effects due to oral administration route. We aim to use ablative fractional laser (AFL) to enable the topical delivery of vismodegib to relevant dermal depths. Pig skin was treated in vitro with a fractional 10,600 nm CO Combination of AFL and vismodegib emulsion substantially enhanced the delivery of drug into the skin. Emulsion formulation alone yielded higher vismodegib skin concentrations compared to vehicle control in superficial and mid-dermis (0-900 µm, P = 0.002-0.015). The over-all highest concentration found (554.5 µmol/L) was reached at 24 hours in superficial (0-300 µm) AFL exposed skin, 7.6-fold higher than vehicle control (P = 0.002) and 9.7-101.6 fold higher than previously reported steady-state plasma concentrations in patients treated with oral vismodegib (5.5-56.9 µmol/L). Compared to intact skin, AFL exposure significantly increased skin concentrations of vismodegib even in deep skin layers (24 h, 900-1,800 µm, emulsion: 8.7-74.3 µmol/L vs. 0.0-0.0 µmol/L, P = 0.004-0.048; vehicle control: 23.7-50.6 µmol/L vs. 0.0-1.6 µmol/L, P = 0.002). The total delivery of vismodegib-emulsion into mid-deep dermal skin layers from 600 to 1,800 µm was for AFL exposed skin 8.2 fold higher than intact skin. Also, delivery of emulsion vismodegib by AFL was time-dependent as seen by the continuous increase in concentrations found over time, with highest uptake detected after 24 hours (4-24 hours, 0-900 µm, P = 0.002-0.004). AFL enhances topical delivery of micro-emulsion formulated vismodegib, reaching concentrations similar to or above plasma concentrations previously reported in patients receiving oral vismodegib. Lasers Surg. Med. 51:79-87, 2019. © 2018 Wiley Periodicals, Inc.
Sections du résumé
BACKGROUND AND OBJECTIVE
Hedgehog inhibitors such as vismodegib are targeted drugs widely used for the treatment of basal cell carcinomas; however, their use is significantly limited by frequent systemic side effects due to oral administration route. We aim to use ablative fractional laser (AFL) to enable the topical delivery of vismodegib to relevant dermal depths.
MATERIALS AND METHODS
Pig skin was treated in vitro with a fractional 10,600 nm CO
RESULTS
Combination of AFL and vismodegib emulsion substantially enhanced the delivery of drug into the skin. Emulsion formulation alone yielded higher vismodegib skin concentrations compared to vehicle control in superficial and mid-dermis (0-900 µm, P = 0.002-0.015). The over-all highest concentration found (554.5 µmol/L) was reached at 24 hours in superficial (0-300 µm) AFL exposed skin, 7.6-fold higher than vehicle control (P = 0.002) and 9.7-101.6 fold higher than previously reported steady-state plasma concentrations in patients treated with oral vismodegib (5.5-56.9 µmol/L). Compared to intact skin, AFL exposure significantly increased skin concentrations of vismodegib even in deep skin layers (24 h, 900-1,800 µm, emulsion: 8.7-74.3 µmol/L vs. 0.0-0.0 µmol/L, P = 0.004-0.048; vehicle control: 23.7-50.6 µmol/L vs. 0.0-1.6 µmol/L, P = 0.002). The total delivery of vismodegib-emulsion into mid-deep dermal skin layers from 600 to 1,800 µm was for AFL exposed skin 8.2 fold higher than intact skin. Also, delivery of emulsion vismodegib by AFL was time-dependent as seen by the continuous increase in concentrations found over time, with highest uptake detected after 24 hours (4-24 hours, 0-900 µm, P = 0.002-0.004).
CONCLUSION
AFL enhances topical delivery of micro-emulsion formulated vismodegib, reaching concentrations similar to or above plasma concentrations previously reported in patients receiving oral vismodegib. Lasers Surg. Med. 51:79-87, 2019. © 2018 Wiley Periodicals, Inc.
Substances chimiques
Anilides
0
Emulsions
0
HhAntag691
0
Pyridines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
79-87Subventions
Organisme : Bispebjerg and Frederiksberg Hospitals Research Fund
Pays : International
Organisme : Det Frie Forskningsråd
ID : DFF - 6110-00637
Pays : International
Informations de copyright
© 2018 Wiley Periodicals, Inc.