Topical Delivery of Nivolumab, a Therapeutic Antibody, by Fractional Laser and Pneumatic Injection

Autor: Daniel P. Persson, Rikke L Christensen, Merete Haedersdal, Uffe H. Olesen, Søren Husted, Silje Haukali Omland
Rok vydání: 2020
Předmět:
Zdroj: Lasers in Surgery and Medicine. 53:154-161
ISSN: 1096-9101
0196-8092
DOI: 10.1002/lsm.23322
Popis: 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 CO2 AFL (20 mJ/mb, 5% density), followed by passive diffusion of nivolumab in a Franz cell (1 mg/ml, 18 hours, n = 6) or treated with EPI (4 bar) for immediate delivery of nivolumab (1 mg/ml, 10 minutes, n = 6). The resulting nivolumab skin concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) at three skin depths (100, 500, and 1500 µm), comparing the uptake from assisted delivery with intact skin. Biodistribution of nivolumab in the skin for all interventions was visualized by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and fluorescence microscopy. 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
Databáze: OpenAIRE
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