Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol
<b>Background:</b> Cannabidiol (CBD) is a highly lipophilic compound with potential therapeutic applications in neurological disorders. However, its poor aqueous solubility and bioavailability, coupled with instability in physiological conditions, significantly limit its clinical use. &l...
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MDPI AG
2025-01-01
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| author | Lucia Grifoni Elisa Landucci Giuseppe Pieraccini Costanza Mazzantini Maria Camilla Bergonzi Domenico E. Pellegrini-Giampietro Anna Rita Bilia |
| author_facet | Lucia Grifoni Elisa Landucci Giuseppe Pieraccini Costanza Mazzantini Maria Camilla Bergonzi Domenico E. Pellegrini-Giampietro Anna Rita Bilia |
| author_sort | Lucia Grifoni |
| collection | DOAJ |
| description | <b>Background:</b> Cannabidiol (CBD) is a highly lipophilic compound with potential therapeutic applications in neurological disorders. However, its poor aqueous solubility and bioavailability, coupled with instability in physiological conditions, significantly limit its clinical use. <b>Objectives</b>: This study aimed to develop and characterize nanovesicles incorporating Tween 20 to enhance CBD encapsulation, stability, and the performance across the blood–brain barrier (BBB). <b>Methods:</b> Nanovesicles were prepared via thin-film hydration followed by sonication and optimized for size, polydispersity index, and zeta potential. Stability studies were conducted under physiological conditions and during storage at 4 °C. In vitro release studies employed the dialysis bag method, while permeability across the BBB was assessed using PAMPA-BBB and the hCMEC/D3-BBB cell line, characterized for brain endothelial phenotype and largely employed as a model of human blood–brain barrier (BBB) function. Cytotoxicity was evaluated via MTT and LDH assays. <b>Results:</b> The quantification of CBD was carried out by HPLC-DAD and HPLC-MS/MS. Nanovesicles with Tween 20 (VS-CBD) exhibited smaller size (65.27 ± 1.27 nm vs. 90.7 ± 0.2), lower polydispersity (0.230 ± 0.005 vs. 0.295 ± 0.003), and higher stability compared to conventional liposomes (L-CBD). VS-CBD achieved high encapsulation efficiency (96.80 ± 0.96%) and recovery (99.89 ± 0.52%). Release studies showed sustained CBD release with Higuchi model fitting (R<sup>2</sup> = 0.9901). Both PAMPA-BBB and hCMEC/D3-BBB cell lines demonstrated an improved controlled permeability of the formulation compared to free CBD. Cytotoxicity tests confirmed the good biocompatibility of VS-CBD formulations. The addition of Tween 20 to nanovesicles enhanced CBD encapsulation, stability, and controlled release. <b>Conclusions:</b> These nanovesicles represent a promising strategy to improve CBD delivery to the brain, offering sustained therapeutic effects and reduced dosing frequency, potentially benefiting the treatment of neurological disorders. |
| format | Article |
| id | doaj-art-e0d5a3452d004207bad362e74dbbdd52 |
| institution | OA Journals |
| issn | 1424-8247 |
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| publishDate | 2025-01-01 |
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| spelling | doaj-art-e0d5a3452d004207bad362e74dbbdd522025-08-20T02:03:28ZengMDPI AGPharmaceuticals1424-82472025-01-0118216010.3390/ph18020160Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with CannabidiolLucia Grifoni0Elisa Landucci1Giuseppe Pieraccini2Costanza Mazzantini3Maria Camilla Bergonzi4Domenico E. Pellegrini-Giampietro5Anna Rita Bilia6Dipartimento di Chimica Ugo Schiff, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Firenze, ItalyDipartimento di Scienze della Salute, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyCentro di Servizi di Spettrometria di Massa (CISM), University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDipartimento di Scienze della Salute, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDipartimento di Chimica Ugo Schiff, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Firenze, ItalyDipartimento di Scienze della Salute, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDipartimento di Chimica Ugo Schiff, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Firenze, Italy<b>Background:</b> Cannabidiol (CBD) is a highly lipophilic compound with potential therapeutic applications in neurological disorders. However, its poor aqueous solubility and bioavailability, coupled with instability in physiological conditions, significantly limit its clinical use. <b>Objectives</b>: This study aimed to develop and characterize nanovesicles incorporating Tween 20 to enhance CBD encapsulation, stability, and the performance across the blood–brain barrier (BBB). <b>Methods:</b> Nanovesicles were prepared via thin-film hydration followed by sonication and optimized for size, polydispersity index, and zeta potential. Stability studies were conducted under physiological conditions and during storage at 4 °C. In vitro release studies employed the dialysis bag method, while permeability across the BBB was assessed using PAMPA-BBB and the hCMEC/D3-BBB cell line, characterized for brain endothelial phenotype and largely employed as a model of human blood–brain barrier (BBB) function. Cytotoxicity was evaluated via MTT and LDH assays. <b>Results:</b> The quantification of CBD was carried out by HPLC-DAD and HPLC-MS/MS. Nanovesicles with Tween 20 (VS-CBD) exhibited smaller size (65.27 ± 1.27 nm vs. 90.7 ± 0.2), lower polydispersity (0.230 ± 0.005 vs. 0.295 ± 0.003), and higher stability compared to conventional liposomes (L-CBD). VS-CBD achieved high encapsulation efficiency (96.80 ± 0.96%) and recovery (99.89 ± 0.52%). Release studies showed sustained CBD release with Higuchi model fitting (R<sup>2</sup> = 0.9901). Both PAMPA-BBB and hCMEC/D3-BBB cell lines demonstrated an improved controlled permeability of the formulation compared to free CBD. Cytotoxicity tests confirmed the good biocompatibility of VS-CBD formulations. The addition of Tween 20 to nanovesicles enhanced CBD encapsulation, stability, and controlled release. <b>Conclusions:</b> These nanovesicles represent a promising strategy to improve CBD delivery to the brain, offering sustained therapeutic effects and reduced dosing frequency, potentially benefiting the treatment of neurological disorders.https://www.mdpi.com/1424-8247/18/2/160cannabidiolnanovesiclesTween 20hCMEC/D3 cell lineenhanced encapsulation and permeationstability |
| spellingShingle | Lucia Grifoni Elisa Landucci Giuseppe Pieraccini Costanza Mazzantini Maria Camilla Bergonzi Domenico E. Pellegrini-Giampietro Anna Rita Bilia Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol Pharmaceuticals cannabidiol nanovesicles Tween 20 hCMEC/D3 cell line enhanced encapsulation and permeation stability |
| title | Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol |
| title_full | Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol |
| title_fullStr | Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol |
| title_full_unstemmed | Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol |
| title_short | Development and Blood–Brain Barrier Penetration of Nanovesicles Loaded with Cannabidiol |
| title_sort | development and blood brain barrier penetration of nanovesicles loaded with cannabidiol |
| topic | cannabidiol nanovesicles Tween 20 hCMEC/D3 cell line enhanced encapsulation and permeation stability |
| url | https://www.mdpi.com/1424-8247/18/2/160 |
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