Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management

Cannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects. This study aimed to encapsulate...

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Authors: El Hammadi, Mazen M., Small Howard, Andrea L., Fernández Arévalo, María Mercedes, Turner, Helen, Martín Banderas, Lucía
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Universidad de Sevilla (US)
Repository:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/175069
Online Access:https://hdl.handle.net/11441/175069
https://doi.org/10.1016/j.ijpharm.2025.125766
Access Level:Open access
Keyword:Cannabigerolic acid
Cannabis-based terpenes
PLGA polymeric nanoparticles
Beta-myrcene
Nerolidol
Beta-caryophyllene
Nanomedicine
Chronic pain
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spelling Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain ManagementEl Hammadi, Mazen M.Small Howard, Andrea L.Fernández Arévalo, María MercedesTurner, HelenMartín Banderas, LucíaCannabigerolic acidCannabis-based terpenesPLGA polymeric nanoparticlesBeta-myrceneNerolidolBeta-caryophylleneNanomedicineChronic painCannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects. This study aimed to encapsulate cannabigerolic acid (CBGA) in poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) and investigate the effects of combining CBGA NPs with cannabis-derived terpene-loaded NPs (myrcene [MC], nerolidol [NL], and caryophyllene [CPh]) for potential applications in pain management. CBGA NPs (152 nm) and terpene-loaded NPs (233–297 nm) were prepared via nanoprecipitation and emulsion-solvent evaporation, respectively, exhibiting a polydispersity index < 0.3 and negative zeta potentials (−23 to −26 mV). Encapsulation efficiency was 98.6 % for CBGA and 13–33 % for terpenes. CBGA release followed a biphasic profile, with ∼ 20 % released within 4 h and sustained release over 72 h. In vitro evaluation used HEK293 cells expressing the nociceptive transient receptor potential vanilloid-1 (TRPV1) channel, a key mediator of pain perception. TRPV1 activation was assessed via calcium influx kinetics (Fluo-4 indicator). The EC50 values were 23.8 µg/mL (CBGA NPs), 8.0 µg/mL (MC NPs), 6.7 µg/mL (NL NPs), and 13.3 µg/mL (CPh NPs). Combinatorial treatments of CBGA NPs with terpene NPs at their respective EC50 concentrations revealed significantly enhanced calcium influx compared to individual NPs, with the strongest interaction observed for CBGA/NL and moderate effects for CBGA/MC. Fluorescence imaging further corroborated these findings. These results suggest that combining CBGA NPs with terpene-loaded NPs could potentiate pain-relief efficacy, offering a promising strategy for advanced therapeutic formulations.ElsevierFarmacia y Tecnología FarmacéuticaUniversidad de SevillaNational Institutes of Health (NIH)2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/175069https://doi.org/10.1016/j.ijpharm.2025.125766reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInternational Journal of Pharmaceutics, 679, 125766.CITIUS-I.3NIH R15 DA051749-01NIH INBRE P20 GM103466https://doi.org/10.1016/j.ijpharm.2025.125766info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1750692026-06-17T12:51:07Z
dc.title.none.fl_str_mv Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
title Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
spellingShingle Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
El Hammadi, Mazen M.
Cannabigerolic acid
Cannabis-based terpenes
PLGA polymeric nanoparticles
Beta-myrcene
Nerolidol
Beta-caryophyllene
Nanomedicine
Chronic pain
title_short Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
title_full Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
title_fullStr Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
title_full_unstemmed Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
title_sort Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
dc.creator.none.fl_str_mv El Hammadi, Mazen M.
Small Howard, Andrea L.
Fernández Arévalo, María Mercedes
Turner, Helen
Martín Banderas, Lucía
author El Hammadi, Mazen M.
author_facet El Hammadi, Mazen M.
Small Howard, Andrea L.
Fernández Arévalo, María Mercedes
Turner, Helen
Martín Banderas, Lucía
author_role author
author2 Small Howard, Andrea L.
Fernández Arévalo, María Mercedes
Turner, Helen
Martín Banderas, Lucía
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Farmacia y Tecnología Farmacéutica
Universidad de Sevilla
National Institutes of Health (NIH)
dc.subject.none.fl_str_mv Cannabigerolic acid
Cannabis-based terpenes
PLGA polymeric nanoparticles
Beta-myrcene
Nerolidol
Beta-caryophyllene
Nanomedicine
Chronic pain
topic Cannabigerolic acid
Cannabis-based terpenes
PLGA polymeric nanoparticles
Beta-myrcene
Nerolidol
Beta-caryophyllene
Nanomedicine
Chronic pain
description Cannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects. This study aimed to encapsulate cannabigerolic acid (CBGA) in poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) and investigate the effects of combining CBGA NPs with cannabis-derived terpene-loaded NPs (myrcene [MC], nerolidol [NL], and caryophyllene [CPh]) for potential applications in pain management. CBGA NPs (152 nm) and terpene-loaded NPs (233–297 nm) were prepared via nanoprecipitation and emulsion-solvent evaporation, respectively, exhibiting a polydispersity index < 0.3 and negative zeta potentials (−23 to −26 mV). Encapsulation efficiency was 98.6 % for CBGA and 13–33 % for terpenes. CBGA release followed a biphasic profile, with ∼ 20 % released within 4 h and sustained release over 72 h. In vitro evaluation used HEK293 cells expressing the nociceptive transient receptor potential vanilloid-1 (TRPV1) channel, a key mediator of pain perception. TRPV1 activation was assessed via calcium influx kinetics (Fluo-4 indicator). The EC50 values were 23.8 µg/mL (CBGA NPs), 8.0 µg/mL (MC NPs), 6.7 µg/mL (NL NPs), and 13.3 µg/mL (CPh NPs). Combinatorial treatments of CBGA NPs with terpene NPs at their respective EC50 concentrations revealed significantly enhanced calcium influx compared to individual NPs, with the strongest interaction observed for CBGA/NL and moderate effects for CBGA/MC. Fluorescence imaging further corroborated these findings. These results suggest that combining CBGA NPs with terpene-loaded NPs could potentiate pain-relief efficacy, offering a promising strategy for advanced therapeutic formulations.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/175069
https://doi.org/10.1016/j.ijpharm.2025.125766
url https://hdl.handle.net/11441/175069
https://doi.org/10.1016/j.ijpharm.2025.125766
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv International Journal of Pharmaceutics, 679, 125766.
CITIUS-I.3
NIH R15 DA051749-01
NIH INBRE P20 GM103466
https://doi.org/10.1016/j.ijpharm.2025.125766
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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