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A Simple and Improved Active Loading Method to Efficiently Encapsulate Staurosporine into Lipid-Based Nanoparticles
Wei-Lun Tang1,2, Weihsu Claire Chen1, Aniruddha Roy1,2
1Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
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.
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