Details

Autor(en) / Beteiligte

• El-Hammadi, Mazen M.
• Small-Howard, Andrea L.
• Jansen, Chad
• Fernández-Arévalo, Mercedes
• Turner, Helen
• Martín-Banderas, Lucía

Titel

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

Ist Teil von

• International journal of pharmaceutics, 2022-03, Vol.616, p.121524-121524, Article 121524

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •Beta-myrcene, beta-caryophyllene, &trans-nerolidol are Cannabis-derived terpenes with therapeutic potential.•Nanocarriers can improve the solubility and bioavailability of these volatile and hydrophobic terpenes.•Poly(lactide-co-glycolide) nanoparticles successfully encapsulated these three terpenes and enhanced activation of TPRV1 receptors.•Combinations of terpene-loaded NP formulations produced significantly higher calcium responses versus combinations of free terpenes. 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.