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 作者： Michael A. Collier,Eric M. Bachelder,Kristy M. Ainslie

Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North CarolinaChapel Hill, USA

 

摘要：Purpose

 

Although doxorubicin (DXR) has been on the market for many years as an anti-cancer drug, a number of serious dose-limiting toxicities hinder its widespread use. To reduce the known toxicities of soluble DXR, various liposomes have been designed including Doxil, Caelyx, and Myocet. Myocet, a non-PEGylated liposomal formulation containing DXR, was found to reduce the toxicities associated with soluble DXR and has been used in Europe and Canada (but not the US) as a first line therapy. While regarded as successful, Myocet does have some formulation drawbacks including stability, drug release, and an arduous formulation and remote loading method for preparation.

 

Methods

 

Our lab has developed a liposomal electrospray process in which formulation and remote loading occurs continuously in one step, cutting down on the total time of production and increasing the drug retention in the liposomes with respect to more conventional methods. Electrosprayed Myocet-like liposomes were then tested in vitro for release kinetics and cytotoxicity with respect to a more conventional formulation method.

 

Results

 

Myocet-like liposomes manufactured via electrospray had similar DXR loadings, hydrodynamic diameters, morphologies, and cytotoxic profiles as their thin-film hydration counterparts, but their release profiles were drastically prolonged.

 

Conclusions

 

Our findings indicate that electrospray is a viable manufacturing procedure to scalably produce Myocet-like liposomes that appear to be more stable than those formulated through thin-film hydration.