Remote loading of preencapsulated drugs into stealth liposomes

Loading drugs into carriers such as liposomes can increase the therapeutic ratio by reducing drug concentrations in normal tissues and raising their concentrations in tumors. Although this strategy has proven advantageous in certain circumstances, many drugs are highly hydrophobic and nonionizable a...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2014-02, Vol.111 (6), p.2283-2288
Main Authors: Sur, Surojit, Fries, Anja C., Kinzler, Kenneth W., Zhou, Shibin, Vogelstein, Bert
Format: Article
Language:English
Subjects:
Antineoplastic Agents - administration & dosage
Antineoplastics
beta-Cyclodextrins - chemistry
Biological Sciences
Cancer
Chemistry, Pharmaceutical
Clinical trials
Coumarins
Cyclodextrins
Dosage
Drug Carriers
Encapsulation
Hydrophobic and Hydrophilic Interactions
Liposomes
Medication administration
Rodents
Solubility
Tissues
Toxicity
Tumors
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Summary:Loading drugs into carriers such as liposomes can increase the therapeutic ratio by reducing drug concentrations in normal tissues and raising their concentrations in tumors. Although this strategy has proven advantageous in certain circumstances, many drugs are highly hydrophobic and nonionizable and cannot be loaded into liposomes through conventional means. We hypothesized that such drugs could be actively loaded into liposomes by encapsulating them into specially designed cyclodextrins. To test this hypothesis, two hydrophobic drugs that had failed phase II clinical trials because of excess toxicity at deliverable doses were evaluated. In both cases, the drugs could be remotely loaded into liposomes after their encapsulation (preloading) into cyclodextrins and administered to mice at higher doses and with greater efficacy than possible with the free drugs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1324135111