Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes
Cannabidiol (CBD) is a promising drug candidate with pleiotropic pharmacological activity, whose low aqueous solubility and unfavorable pharmacokinetics have presented obstacles to its full clinical implementation. The rational design of nanocarriers, including niosomes for CBD encapsulation, can pr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/10/2414 |
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| author | Viliana Gugleva Katerina Ahchiyska Dilyana Georgieva Rositsa Mihaylova Spiro Konstantinov Erik Dimitrov Natalia Toncheva-Moncheva Stanislav Rangelov Aleksander Forys Barbara Trzebicka Denitsa Momekova |
| author_facet | Viliana Gugleva Katerina Ahchiyska Dilyana Georgieva Rositsa Mihaylova Spiro Konstantinov Erik Dimitrov Natalia Toncheva-Moncheva Stanislav Rangelov Aleksander Forys Barbara Trzebicka Denitsa Momekova |
| author_sort | Viliana Gugleva |
| collection | DOAJ |
| description | Cannabidiol (CBD) is a promising drug candidate with pleiotropic pharmacological activity, whose low aqueous solubility and unfavorable pharmacokinetics have presented obstacles to its full clinical implementation. The rational design of nanocarriers, including niosomes for CBD encapsulation, can provide a plausible approach to overcoming these limitations. The present study is focused on exploring the feasibility of copolymer-modified niosomes as platforms for systemic delivery of CBD. To confer steric stabilization, the niosomal membranes were grafted with newly synthesized amphiphilic linear or star-shaped 3- and 4-arm star-shaped copolymers based on polyglycidol (PG) and poly(ε-caprolactone) (PCL) blocks. The niosomes were prepared by film hydration method and were characterized by DLS, cryo-TEM, encapsulation efficacy, and in vitro release. Free and formulated cannabidiol were further investigated for cytotoxicity and pro-apoptotic and anti-inflammatory activities in vitro in three human tumor cell lines. The optimal formulation, based on Tween 60:Span60:Chol (3.5:3.5:3 molar ration) modified with 2.5 mol% star-shaped 3-arm copolymer, is characterized by a size of 235 nm, high encapsulation of CBD (94%), and controlled release properties. Niosomal cannabidiol retained the antineoplastic activity of the free agent, but noteworthy superior apoptogenic and inflammatory biomarker-modulating effects were established at equieffective exposure vs. the free drug. Specific alterations in key signaling molecules, implicated in programmed cell death, cancer cell biology, and inflammation, were recorded with the niosomal formulations. |
| first_indexed | 2024-03-10T20:58:49Z |
| format | Article |
| id | doaj.art-8a345125d311436e91da42b4710e0722 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:58:49Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8a345125d311436e91da42b4710e07222023-11-19T17:44:10ZengMDPI AGPharmaceutics1999-49232023-10-011510241410.3390/pharmaceutics15102414Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating NiosomesViliana Gugleva0Katerina Ahchiyska1Dilyana Georgieva2Rositsa Mihaylova3Spiro Konstantinov4Erik Dimitrov5Natalia Toncheva-Moncheva6Stanislav Rangelov7Aleksander Forys8Barbara Trzebicka9Denitsa Momekova10Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University of Varna, 84 Tsar Osvoboditel Str., 9000 Varna, BulgariaDepartment of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, bl.103 Akad. G. Bonchev Str., 1113 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, bl.103 Akad. G. Bonchev Str., 1113 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, bl.103 Akad. G. Bonchev Str., 1113 Sofia, BulgariaCentre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowskiej 34, 41-819 Zabrze, PolandCentre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowskiej 34, 41-819 Zabrze, PolandDepartment of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaCannabidiol (CBD) is a promising drug candidate with pleiotropic pharmacological activity, whose low aqueous solubility and unfavorable pharmacokinetics have presented obstacles to its full clinical implementation. The rational design of nanocarriers, including niosomes for CBD encapsulation, can provide a plausible approach to overcoming these limitations. The present study is focused on exploring the feasibility of copolymer-modified niosomes as platforms for systemic delivery of CBD. To confer steric stabilization, the niosomal membranes were grafted with newly synthesized amphiphilic linear or star-shaped 3- and 4-arm star-shaped copolymers based on polyglycidol (PG) and poly(ε-caprolactone) (PCL) blocks. The niosomes were prepared by film hydration method and were characterized by DLS, cryo-TEM, encapsulation efficacy, and in vitro release. Free and formulated cannabidiol were further investigated for cytotoxicity and pro-apoptotic and anti-inflammatory activities in vitro in three human tumor cell lines. The optimal formulation, based on Tween 60:Span60:Chol (3.5:3.5:3 molar ration) modified with 2.5 mol% star-shaped 3-arm copolymer, is characterized by a size of 235 nm, high encapsulation of CBD (94%), and controlled release properties. Niosomal cannabidiol retained the antineoplastic activity of the free agent, but noteworthy superior apoptogenic and inflammatory biomarker-modulating effects were established at equieffective exposure vs. the free drug. Specific alterations in key signaling molecules, implicated in programmed cell death, cancer cell biology, and inflammation, were recorded with the niosomal formulations.https://www.mdpi.com/1999-4923/15/10/2414star-shaped polyglycidol- poly(ε-caprolactone) copolymerscopolymer-modified niosomessteric stabilizationEPR effectcannabidiolapoptosis |
| spellingShingle | Viliana Gugleva Katerina Ahchiyska Dilyana Georgieva Rositsa Mihaylova Spiro Konstantinov Erik Dimitrov Natalia Toncheva-Moncheva Stanislav Rangelov Aleksander Forys Barbara Trzebicka Denitsa Momekova Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes Pharmaceutics star-shaped polyglycidol- poly(ε-caprolactone) copolymers copolymer-modified niosomes steric stabilization EPR effect cannabidiol apoptosis |
| title | Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes |
| title_full | Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes |
| title_fullStr | Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes |
| title_full_unstemmed | Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes |
| title_short | Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes |
| title_sort | development characterization and pharmacological evaluation of cannabidiol loaded long circulating niosomes |
| topic | star-shaped polyglycidol- poly(ε-caprolactone) copolymers copolymer-modified niosomes steric stabilization EPR effect cannabidiol apoptosis |
| url | https://www.mdpi.com/1999-4923/15/10/2414 |
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