Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex
This work was aimed at enhancing butamben (BTB) anesthetic efficacy by the “drug-in cyclodextrin (CD)-in deformable liposomes” strategy. In the study, phase-solubility studies with natural (α-, β-, γ-) and derivative (hydroxypropyl-α-and β-, sulfobutylether-β, methyl-β) CDs evidenced the highest BTB...
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MDPI AG
2021-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/6/872 |
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| author | Paola Mura Francesca Maestrelli Marzia Cirri Giulia Nerli Lorenzo Di Cesare Mannelli Carla Ghelardini Natascia Mennini |
| author_facet | Paola Mura Francesca Maestrelli Marzia Cirri Giulia Nerli Lorenzo Di Cesare Mannelli Carla Ghelardini Natascia Mennini |
| author_sort | Paola Mura |
| collection | DOAJ |
| description | This work was aimed at enhancing butamben (BTB) anesthetic efficacy by the “drug-in cyclodextrin (CD)-in deformable liposomes” strategy. In the study, phase-solubility studies with natural (α-, β-, γ-) and derivative (hydroxypropyl-α-and β-, sulfobutylether-β, methyl-β) CDs evidenced the highest BTB affinity for βCD and its derivatives and indicated methyl-βCD (RAMEB) as the best carrier. Drug-RAMEB complexes were prepared by different techniques and were characterized for solid-state and dissolution properties. The best BTB–RAMEB product was chosen for entrapment in the aqueous core of deformable liposomes containing stearylamine, either alone or with sodium cholate, as edge activators. Double-loaded (DL) liposomes, bearing the lipophilic drug (0.5% <i>w</i>/<i>v</i>) in the bilayer and its hydrophilic RAMEB complex (0.5% <i>w</i>/<i>v</i>) in the aqueous core, were compared to single-loaded (SL) liposomes bearing 1% <i>w</i>/<i>v</i> plain drug in the bilayer. All vesicles showed homogeneous dimensions (i.e., below 300 nm), high deformability, and excellent entrapment efficiency. DL-liposomes were more effective than SL ones in limiting drug leakage (<5% vs. >10% after a 3 months storage at 4 °C). In vivo experiments in rabbits proved that all liposomal formulations significantly (<i>p</i> < 0.05) increased the intensity and duration of drug anesthetic action compared to its hydroalcoholic solution; however, DL liposomes were significantly (<i>p</i> < 0.05) more effective than SL ones in prolonging BTB anesthetic effect, owing to the presence of the drug-RAMEB complex in the vesicle core, acting as a reservoir. DL liposomes containing both edge activators were found to have the best performance. |
| first_indexed | 2024-03-10T10:27:35Z |
| format | Article |
| id | doaj.art-a200ae2958a04c62b25aa54a31b77b1c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T10:27:35Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a200ae2958a04c62b25aa54a31b77b1c2023-11-21T23:54:55ZengMDPI AGPharmaceutics1999-49232021-06-0113687210.3390/pharmaceutics13060872Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin ComplexPaola Mura0Francesca Maestrelli1Marzia Cirri2Giulia Nerli3Lorenzo Di Cesare Mannelli4Carla Ghelardini5Natascia Mennini6Department of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, ItalyDepartment of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, ItalyDepartment of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, ItalyDepartment of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Florence, 50139 Florence, ItalyDepartment of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Florence, 50139 Florence, ItalyDepartment of Chemistry, University of Florence, via Schiff 6, Sesto Fiorentino, 50019 Florence, ItalyThis work was aimed at enhancing butamben (BTB) anesthetic efficacy by the “drug-in cyclodextrin (CD)-in deformable liposomes” strategy. In the study, phase-solubility studies with natural (α-, β-, γ-) and derivative (hydroxypropyl-α-and β-, sulfobutylether-β, methyl-β) CDs evidenced the highest BTB affinity for βCD and its derivatives and indicated methyl-βCD (RAMEB) as the best carrier. Drug-RAMEB complexes were prepared by different techniques and were characterized for solid-state and dissolution properties. The best BTB–RAMEB product was chosen for entrapment in the aqueous core of deformable liposomes containing stearylamine, either alone or with sodium cholate, as edge activators. Double-loaded (DL) liposomes, bearing the lipophilic drug (0.5% <i>w</i>/<i>v</i>) in the bilayer and its hydrophilic RAMEB complex (0.5% <i>w</i>/<i>v</i>) in the aqueous core, were compared to single-loaded (SL) liposomes bearing 1% <i>w</i>/<i>v</i> plain drug in the bilayer. All vesicles showed homogeneous dimensions (i.e., below 300 nm), high deformability, and excellent entrapment efficiency. DL-liposomes were more effective than SL ones in limiting drug leakage (<5% vs. >10% after a 3 months storage at 4 °C). In vivo experiments in rabbits proved that all liposomal formulations significantly (<i>p</i> < 0.05) increased the intensity and duration of drug anesthetic action compared to its hydroalcoholic solution; however, DL liposomes were significantly (<i>p</i> < 0.05) more effective than SL ones in prolonging BTB anesthetic effect, owing to the presence of the drug-RAMEB complex in the vesicle core, acting as a reservoir. DL liposomes containing both edge activators were found to have the best performance.https://www.mdpi.com/1999-4923/13/6/872butambendeformable liposomesstearylaminesodium cholatedouble-loadingin vivo anesthetic effect |
| spellingShingle | Paola Mura Francesca Maestrelli Marzia Cirri Giulia Nerli Lorenzo Di Cesare Mannelli Carla Ghelardini Natascia Mennini Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex Pharmaceutics butamben deformable liposomes stearylamine sodium cholate double-loading in vivo anesthetic effect |
| title | Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex |
| title_full | Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex |
| title_fullStr | Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex |
| title_full_unstemmed | Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex |
| title_short | Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex |
| title_sort | improvement of butamben anesthetic efficacy by the development of deformable liposomes bearing the drug as cyclodextrin complex |
| topic | butamben deformable liposomes stearylamine sodium cholate double-loading in vivo anesthetic effect |
| url | https://www.mdpi.com/1999-4923/13/6/872 |
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