Topical Delivery of Nivolumab, a Therapeutic Antibody, by Fractional Laser and Pneumatic Injection.
PD-1 inhibitor
ablative fractional laser
biodistribution
dermatology
drug delivery
electronically controlled pneumatic injection
laser ablation-inductively coupled plasma-mass spectrometry
needle-free injection
nivolumab
skin cancer
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 2021
01 2021
Historique:
received:
07
07
2020
revised:
27
08
2020
accepted:
09
09
2020
pubmed:
1
10
2020
medline:
29
10
2021
entrez:
30
9
2020
Statut:
ppublish
Résumé
PD-L1 is a tumor ligand that binds to the PD-1 receptor on immune cells, thereby inhibiting the antitumor immune response. The antibody nivolumab is a PD-1 inhibitor, Food and Drug Administration approved for systemic treatment of several aggressive cancer types. Topically applied nivolumab may hold potential as a future strategy to treat keratinocyte cancer, but its molecular properties preclude unassisted topical uptake. The aim of this study was to investigate uptake and biodistribution of topically delivered nivolumab, assisted by two physical enhancement techniques with different delivery kinetics; ablative fractional laser (AFL) and electronically controlled pneumatic injection (EPI). In vitro porcine skin was exposed to CO Delivery of nivolumab by AFL-assisted passive diffusion and immediate EPI both resulted in significantly enhanced uptake of nivolumab in all skin depths compared with intact skin (P < 0.05). With AFL, nivolumab concentrations reached 86.3 µg/cm AFL-assisted passive diffusion and immediate EPI-assisted delivery show the potential to deliver therapeutic antibodies locally. Future in vivo and pharmacokinetic studies would reveal the full potential for topical antibody delivery by energy-based devices. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
Sections du résumé
BACKGROUND AND OBJECTIVES
PD-L1 is a tumor ligand that binds to the PD-1 receptor on immune cells, thereby inhibiting the antitumor immune response. The antibody nivolumab is a PD-1 inhibitor, Food and Drug Administration approved for systemic treatment of several aggressive cancer types. Topically applied nivolumab may hold potential as a future strategy to treat keratinocyte cancer, but its molecular properties preclude unassisted topical uptake. The aim of this study was to investigate uptake and biodistribution of topically delivered nivolumab, assisted by two physical enhancement techniques with different delivery kinetics; ablative fractional laser (AFL) and electronically controlled pneumatic injection (EPI).
STUDY DESIGN/MATERIALS AND METHODS
In vitro porcine skin was exposed to CO
RESULTS
Delivery of nivolumab by AFL-assisted passive diffusion and immediate EPI both resulted in significantly enhanced uptake of nivolumab in all skin depths compared with intact skin (P < 0.05). With AFL, nivolumab concentrations reached 86.3 µg/cm
CONCLUSIONS
AFL-assisted passive diffusion and immediate EPI-assisted delivery show the potential to deliver therapeutic antibodies locally. Future in vivo and pharmacokinetic studies would reveal the full potential for topical antibody delivery by energy-based devices. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
Substances chimiques
Nivolumab
31YO63LBSN
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-161Informations de copyright
© 2020 Wiley Periodicals LLC.
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