Abstract
PurposeIn order to attenuate the drug release rate, a single freeze-thaw step was previously shown to convert encapsulated drug into a single nanocrystal within each liposome vesicle. The goal of this study was to alter the nanocrystalline character, and thus the drug encapsulation state and release profile, by addition of surfactant prior to freeze-thaw.MethodsA liposomal ciprofloxacin (CFI) formulation was modified by the addition of surfactant and frozen. After thawing, these formulations were characterized in terms of drug encapsulation by centrifugation-filtration, liposome structure by cryo-TEM imaging, vesicle size by dynamic light scattering, and in vitro release (IVR) performance.ResultsThe addition of increasing levels of polysorbate 20 (0.05 to 0.4%) or Brij 30 (0.05 to 0.3%) to the CFI preparations followed by subsequent freeze-thaw, resulted in a greater proportion of vesicles without drug nanocrystals and reduced the extent of growth of the nanocrystals thus leading to modified release rates including an increase in the ratio of non-encapsulated to sustained release of drug.ConclusionsThis study provides another lever to achieve the desired release rate profile from a liposomal formulation by addition of surfactant and subsequent freeze-thaw, and thus may provide a personalized approach to treating patients.
Highlights
Liposomes are lipid vesicles, typically composed of bilayers of phospholipids and sterols
The control and the thawed CFI samples were diluted to ~5 mg/ml (10 mg/ml liposomes) with water and 3 μl of each sample was applied to a glow discharge Quantifoil carbon grid (Jena, Germany) in a chamber controlled to 22°C and 100% RH
This initial Bburst^ was followed by a slower initial release profile compared to that for the unfrozen control CFI sample, as would be expected if drug nanocrystals had formed as a result of freeze-thaw (Fig. 7b)
Summary
Typically composed of bilayers of phospholipids and sterols. Hydrophilic drugs can be loaded into the aqueous interior of the vesicles while lipid soluble drugs can be associated with the lipid bilayer. Liposomal products have been designed to improve the safety and efficacy of treatment, through modification of the pharmacokinetics and biodistribution of the associated API [1, 2]. Liposomes represent a versatile class of drug carriers which are continuing to evolve to address new therapeutic opportunities. These studies describe another step in the liposome evolution process by expanding the formulation toolbox to modulate the drug release profile with only relatively minor changes in composition of the formulation. The key impact appears to be the modification of the solid state of the encapsulated drug, in this example ciprofloxacin
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