Topical delivery of PD-1 inhibitors with laser-assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns.
LA-ICP-MS
PD-1 inhibitors
ablative fractional laser
dermatology
drug delivery
imaging
nivolumab
pharmacokinetics
skin cancer
topical delivery
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 2022
01 2022
Historique:
revised:
16
11
2021
received:
20
08
2021
accepted:
19
11
2021
pubmed:
4
12
2021
medline:
28
1
2022
entrez:
3
12
2021
Statut:
ppublish
Résumé
Current cancer immunotherapeutic treatment with PD-1 inhibitors is administered systemically. However, a local treatment strategy may be advantageous as it could provide targeted drug delivery as well as attenuate side effects seen with systemic treatments. For keratinocyte cancers, where surgical excision is not always applicable, an alternate local treatment approach would be beneficial. This study aims to examine cutaneous pharmacokinetics and biodistribution of the PD-1 inhibitor nivolumab, locally delivered either by ablative fractional laser (AFL)-assisted passive diffusion or active intradermal injection, in vivo. In vivo pig skin was either exposed to CO Our in vivo study revealed different pharmacokinetic and biodistribution patterns for the AFL- and injection techniques. A superficial horizontal band-like uptake of nivolumab was provided with AFL-assisted passive diffusion whereas a deep focal deposition was seen with active intradermal injection, compared with controls showing remnant deposition on the skin surface. AFL-assisted nivolumab uptake in upper dermis peaked after 4 hours (p < 0.01). The cutaneous concentration of nivolumab achieved by intradermal injection was markedly higher than with AFL, the highest deposition with intradermal injection was detected at time 0 hours in both upper and deep dermis (p < 0.01) and decreased throughout the study period, although the concentration remained higher compared with saline control injections at all time points (0 hours -2 d) (p < 0.01). Local cutaneous delivery of nivolumab with either AFL or intradermal injection revealed two different pharmacokinetic and biodistribution patterns. Passive AFL-assisted diffusion of nivolumab resulted in enhanced uptake after 4 hours, while intradermal actively injected nivolumab showed immediate enhanced cutaneous deposition with retention up to 2 days after injection. The two local delivery techniques show potential for development of individualized treatment strategies depending on the clinical tumor appearance.
Sections du résumé
BACKGROUND AND OBJECTIVES
Current cancer immunotherapeutic treatment with PD-1 inhibitors is administered systemically. However, a local treatment strategy may be advantageous as it could provide targeted drug delivery as well as attenuate side effects seen with systemic treatments. For keratinocyte cancers, where surgical excision is not always applicable, an alternate local treatment approach would be beneficial. This study aims to examine cutaneous pharmacokinetics and biodistribution of the PD-1 inhibitor nivolumab, locally delivered either by ablative fractional laser (AFL)-assisted passive diffusion or active intradermal injection, in vivo.
MATERIALS AND METHODS
In vivo pig skin was either exposed to CO
RESULTS
Our in vivo study revealed different pharmacokinetic and biodistribution patterns for the AFL- and injection techniques. A superficial horizontal band-like uptake of nivolumab was provided with AFL-assisted passive diffusion whereas a deep focal deposition was seen with active intradermal injection, compared with controls showing remnant deposition on the skin surface. AFL-assisted nivolumab uptake in upper dermis peaked after 4 hours (p < 0.01). The cutaneous concentration of nivolumab achieved by intradermal injection was markedly higher than with AFL, the highest deposition with intradermal injection was detected at time 0 hours in both upper and deep dermis (p < 0.01) and decreased throughout the study period, although the concentration remained higher compared with saline control injections at all time points (0 hours -2 d) (p < 0.01).
CONCLUSION
Local cutaneous delivery of nivolumab with either AFL or intradermal injection revealed two different pharmacokinetic and biodistribution patterns. Passive AFL-assisted diffusion of nivolumab resulted in enhanced uptake after 4 hours, while intradermal actively injected nivolumab showed immediate enhanced cutaneous deposition with retention up to 2 days after injection. The two local delivery techniques show potential for development of individualized treatment strategies depending on the clinical tumor appearance.
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
170-181Informations de copyright
© 2021 Wiley Periodicals LLC.
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