Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist
An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT6 receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic N-arylsulfonylindole that has demonstrated potent 5-HT6 receptor antagonist activity, but i...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | International Journal of Pharmaceutics: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156724000689 |
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| author | María Javiera Alvarez-Figueroa Francisco Nuñez-Navarro Gonzalo Recabarren-Gajardo José Vicente González-Aramundiz |
| author_facet | María Javiera Alvarez-Figueroa Francisco Nuñez-Navarro Gonzalo Recabarren-Gajardo José Vicente González-Aramundiz |
| author_sort | María Javiera Alvarez-Figueroa |
| collection | DOAJ |
| description | An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT6 receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic N-arylsulfonylindole that has demonstrated potent 5-HT6 receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI<0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, in vitro studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10−8 cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10. |
| format | Article |
| id | doaj-art-5d0416b9d5464a19b50949f2a837c0d1 |
| institution | Kabale University |
| issn | 2590-1567 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj-art-5d0416b9d5464a19b50949f2a837c0d12024-12-17T05:00:41ZengElsevierInternational Journal of Pharmaceutics: X2590-15672024-12-018100296Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonistMaría Javiera Alvarez-Figueroa0Francisco Nuñez-Navarro1Gonzalo Recabarren-Gajardo2José Vicente González-Aramundiz3Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile; Corresponding authors at: Facultad de Química y de Farmacia, Escuela de Farmacia, Pontificia Universidad Católica de Chile, Vicuña Mackena 4860, CP:7820436, Macul. Santiago, Chile.Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile; Centro Interdisciplinario de Neurociencias, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile; Centro de Investigación en Nanotecnología y Materiales Avanzados ''CIEN-UC '', Pontificia Universidad Católica de Chile, Santiago, Chile; Corresponding authors at: Facultad de Química y de Farmacia, Escuela de Farmacia, Pontificia Universidad Católica de Chile, Vicuña Mackena 4860, CP:7820436, Macul. Santiago, Chile.An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT6 receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic N-arylsulfonylindole that has demonstrated potent 5-HT6 receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI<0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, in vitro studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10−8 cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.http://www.sciencedirect.com/science/article/pii/S2590156724000689Lipid nanocapsulesPAMPA-BBBBrain permeabilityArylsulfonylindoles5-HT6 receptor |
| spellingShingle | María Javiera Alvarez-Figueroa Francisco Nuñez-Navarro Gonzalo Recabarren-Gajardo José Vicente González-Aramundiz Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist International Journal of Pharmaceutics: X Lipid nanocapsules PAMPA-BBB Brain permeability Arylsulfonylindoles 5-HT6 receptor |
| title | Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist |
| title_full | Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist |
| title_fullStr | Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist |
| title_full_unstemmed | Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist |
| title_short | Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist |
| title_sort | design of an innovative nanovehicle to enhance brain permeability of a novel 5 ht6 receptor antagonist |
| topic | Lipid nanocapsules PAMPA-BBB Brain permeability Arylsulfonylindoles 5-HT6 receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2590156724000689 |
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