Potential use for chronic pain: Poly(Ethylene Glycol)-Poly(Lactic-Co-Glycolic Acid) nanoparticles enhance the effects of Cannabis-Based terpenes on calcium influx in TRPV1-Expressing cells

The objective of these in vitro studies was to investigate the impact of the encapsulation of three cannabis-based terpenes, namely β-myrcene (MC), β-caryophyllene (CPh), and nerolidol (NL), on their potential efficacy in pain management. Terpene-encapsulated poly(ethylene glycol)-poly(lactic-co-gly...

ver descrição completa

Detalhes bibliográficos
Autores: El-Hammadi, Mazen M., Small-Howard, Andrea L., Jansen, Chad, Fernández-Arévalo, Mercedes, Turner, Helen, Martín-Banderas, Lucía
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/307182
Acesso em linha:http://hdl.handle.net/10261/307182
https://api.elsevier.com/content/abstract/scopus_id/85123827430
Access Level:acceso abierto
Palavra-chave:Beta-caryophyllene
Beta-myrcene
Cannabis-based terpenes
Chronic pain
Nanomedicine
Nerolidol
PLGA polymeric nanoparticles
Descrição
Resumo:The objective of these in vitro studies was to investigate the impact of the encapsulation of three cannabis-based terpenes, namely β-myrcene (MC), β-caryophyllene (CPh), and nerolidol (NL), on their potential efficacy in pain management. Terpene-encapsulated poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) were prepared by an emulsion-solvent evaporation method. The terpene-loaded NPs were examined in HEK293 cells that express the nociceptive transient receptor potential vanilloid-1 (TRPV1), an ion channel involved in pain perception. TRPV1 activation was assessed by monitoring calcium influx kinetics over 1 h in cells pre-treated with the fluorescent indicator Fluo-4. In addition, the fluorescence intensity changes induced by the NPs in living cells were also explored by a fluorescence microscope. Furthermore, the cytotoxicity of the terpene-loaded NPs was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl tetrazolium bromide (MTT) proliferation assay. The terpene-loaded NPs had a diameter in the range of 250-350 nm and a zeta potential of approximately -20 mV. The encapsulation efficiency was 18.5%, 51.3%, and 60.3% for MC, NL, and CPh NPs, respectively. The nano-formulations significantly increased the fluorescence intensity in comparison with free terpenes. Furthermore, combinations of terpene-loaded NPs produced significantly higher calcium responses when compared to combinations of free terpenes. Similar findings were shown by the fluorescence images. In conclusion, the terpene-PLGA NPs can be promising therapeutics for more effective pain management.