Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex.

Article Details

Citation
Copy to clipboard

Mura P, Maestrelli F, Cirri M, Nerli G, Di Cesare Mannelli L, Ghelardini C, Mennini N

Improvement of Butamben Anesthetic Efficacy by the Development of Deformable Liposomes Bearing the Drug as Cyclodextrin Complex.

Pharmaceutics. 2021 Jun 12;13(6). pii: pharmaceutics13060872. doi: 10.3390/pharmaceutics13060872.

PubMed ID
34204807 [ View in PubMed
]
Abstract

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 (alpha-, beta-, gamma-) and derivative (hydroxypropyl-alpha-and beta-, sulfobutylether-beta, methyl-beta) CDs evidenced the highest BTB affinity for betaCD and its derivatives and indicated methyl-betaCD (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% w/v) in the bilayer and its hydrophilic RAMEB complex (0.5% w/v) in the aqueous core, were compared to single-loaded (SL) liposomes bearing 1% w/v 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 degrees C). In vivo experiments in rabbits proved that all liposomal formulations significantly (p < 0.05) increased the intensity and duration of drug anesthetic action compared to its hydroalcoholic solution; however, DL liposomes were significantly (p < 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.

DrugBank Data that Cites this Article

Drugs