Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain
Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic aci...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/5275 |
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| author | Nathalie M. Malewicz Zahra Rattray Sebastian Oeck Sebastian Jung Vicente Escamilla-Rivera Zeming Chen Xiangjun Tang Jiangbing Zhou Robert H. LaMotte |
| author_facet | Nathalie M. Malewicz Zahra Rattray Sebastian Oeck Sebastian Jung Vicente Escamilla-Rivera Zeming Chen Xiangjun Tang Jiangbing Zhou Robert H. LaMotte |
| author_sort | Nathalie M. Malewicz |
| collection | DOAJ |
| description | Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent. |
| first_indexed | 2024-03-10T04:02:32Z |
| format | Article |
| id | doaj.art-856768db29994f13985633653c1b755b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:02:32Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-856768db29994f13985633653c1b755b2023-11-23T08:29:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-01239527510.3390/ijms23095275Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat PainNathalie M. Malewicz0Zahra Rattray1Sebastian Oeck2Sebastian Jung3Vicente Escamilla-Rivera4Zeming Chen5Xiangjun Tang6Jiangbing Zhou7Robert H. LaMotte8Department of Anesthesiology, Yale University School of Medicine, 330 Cedar St, New Haven, CT 06510, USAStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Anesthesiology, Yale University School of Medicine, 330 Cedar St, New Haven, CT 06510, USADepartment of Anesthesiology, Yale University School of Medicine, 330 Cedar St, New Haven, CT 06510, USADepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USADepartment of Anesthesiology, Yale University School of Medicine, 330 Cedar St, New Haven, CT 06510, USABackground: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.https://www.mdpi.com/1422-0067/23/9/5275capsaicinnanoparticleshumanpruritogensdesensitizationitch |
| spellingShingle | Nathalie M. Malewicz Zahra Rattray Sebastian Oeck Sebastian Jung Vicente Escamilla-Rivera Zeming Chen Xiangjun Tang Jiangbing Zhou Robert H. LaMotte Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain International Journal of Molecular Sciences capsaicin nanoparticles human pruritogens desensitization itch |
| title | Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain |
| title_full | Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain |
| title_fullStr | Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain |
| title_full_unstemmed | Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain |
| title_short | Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain |
| title_sort | topical capsaicin in poly lactic co glycolic acid plga nanoparticles decreases acute itch and heat pain |
| topic | capsaicin nanoparticles human pruritogens desensitization itch |
| url | https://www.mdpi.com/1422-0067/23/9/5275 |
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