NDLI: A Simple and Improved Active Loading Method to Efficiently Encapsulate Staurosporine into Lipid-Based Nanoparticles for Enhanced Therapy of Multidrug Resistant Cancer

Content Provider	Springer Nature Link
Author	Tang, Wei Lun Chen, Weihsu Claire Roy, Aniruddha Undzys, Elijus Li, Shyh Dar
Copyright Year	2016
Abstract	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.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.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.This simple and efficient drug loading method produced a stable LNP formulation for STS that was effective for cancer treatment.
Starting Page	1104
Ending Page	1114
Page Count	11
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	33
Issue Number	5
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2016-01-12
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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