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 h...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2021-06-01T00:00:00Z.
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| Summary: | 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. |
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| Item Description: | 10.3390/pharmaceutics13060872 1999-4923 |