Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization
Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperal...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/4/339 |
| _version_ | 1797570999809474560 |
|---|---|
| author | Carmelo Puglia Debora Santonocito Angela Bonaccorso Teresa Musumeci Barbara Ruozi Rosario Pignatello Claudia Carbone Carmela Parenti Santina Chiechio |
| author_facet | Carmelo Puglia Debora Santonocito Angela Bonaccorso Teresa Musumeci Barbara Ruozi Rosario Pignatello Claudia Carbone Carmela Parenti Santina Chiechio |
| author_sort | Carmelo Puglia |
| collection | DOAJ |
| description | Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. Methods: CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). Results: CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. Conclusions: Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor. |
| first_indexed | 2024-03-10T20:34:17Z |
| format | Article |
| id | doaj.art-d3de4d45373f40abba27c122dc8271fb |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:34:17Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d3de4d45373f40abba27c122dc8271fb2023-11-19T21:12:44ZengMDPI AGPharmaceutics1999-49232020-04-0112433910.3390/pharmaceutics12040339Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 DefunctionalizationCarmelo Puglia0Debora Santonocito1Angela Bonaccorso2Teresa Musumeci3Barbara Ruozi4Rosario Pignatello5Claudia Carbone6Carmela Parenti7Santina Chiechio8Dipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, 41100 Modena, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyDipartimento di Scienze del Farmaco, Università di Catania, 95100 Catania, ItalyBackground: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. Methods: CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). Results: CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. Conclusions: Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor.https://www.mdpi.com/1999-4923/12/4/339capsaicinTRPV1 agonistlipid nanocarrier (LN)atomic force microscopy (AFM)in vitro releasespontaneous pain |
| spellingShingle | Carmelo Puglia Debora Santonocito Angela Bonaccorso Teresa Musumeci Barbara Ruozi Rosario Pignatello Claudia Carbone Carmela Parenti Santina Chiechio Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization Pharmaceutics capsaicin TRPV1 agonist lipid nanocarrier (LN) atomic force microscopy (AFM) in vitro release spontaneous pain |
| title | Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization |
| title_full | Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization |
| title_fullStr | Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization |
| title_full_unstemmed | Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization |
| title_short | Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization |
| title_sort | lipid nanoparticle inclusion prevents capsaicin induced trpv1 defunctionalization |
| topic | capsaicin TRPV1 agonist lipid nanocarrier (LN) atomic force microscopy (AFM) in vitro release spontaneous pain |
| url | https://www.mdpi.com/1999-4923/12/4/339 |
| work_keys_str_mv | AT carmelopuglia lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT deborasantonocito lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT angelabonaccorso lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT teresamusumeci lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT barbararuozi lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT rosariopignatello lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT claudiacarbone lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT carmelaparenti lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization AT santinachiechio lipidnanoparticleinclusionpreventscapsaicininducedtrpv1defunctionalization |