A Simple and Improved Active Loading Method to Efficiently Encapsulate Staurosporine into Lipid-Based Nanoparticles for Enhanced Therapy of Multidrug Resistant Cancer.
Pharm Res
; 33(5): 1104-14, 2016 May.
Article
in En
| MEDLINE
| ID: mdl-26758590
ABSTRACT
PURPOSE:
This study was aimed at developing a new active loading method to stably encapsulate staurosporine (STS), a water insoluble drug, into lipid-based nanoparticles (LNPs) for drug targeting to tumors.METHODS:
A limited amount of DMSO was included during the active loading process to prevent precipitation and facilitate the loading of insoluble STS into the aqueous core of a LNP. The drug loading kinetics under various conditions was studied and the STS-LNPs were characterized by size, drug-to-lipid ratio, drug release kinetics and in vitro potency. The antitumor efficacy of the STS-LNPs was compared with free STS in a mouse model.RESULTS:
The drug loading efficiency reached 100% within 15 min of incubation at a drug-to-lipid ratio of 0.31 (mol) via an ammonium gradient. STS formed nano-aggregates inside the aqueous core of the LNPs and was stably retained upon storage and in the presence of serum. A 3-fold higher dose of the STS-LNPs could be tolerated by BALB/c mice compared with free STS, leading to nearly complete growth inhibition of a multidrug resistant breast tumor, while free STS only exhibited moderate activity.CONCLUSION:
This simple and efficient drug loading method produced a stable LNP formulation for STS that was effective for cancer treatment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staurosporine
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Protein Kinase Inhibitors
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Nanoparticles
/
Lipids
/
Liposomes
/
Neoplasms
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Pharm Res
Year:
2016
Document type:
Article
Affiliation country:
Canada