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Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy.
- Source :
-
Drug delivery [Drug Deliv] 2018 Nov; Vol. 25 (1), pp. 611-622. - Publication Year :
- 2018
-
Abstract
- To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as 'micelle pool' drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-loading to the pre-loading method , in which drug in micelles shifted onto the bilayer membrane was an additional positive of this delivery system. It was observed that the drug amphiphilicity and interaction of micelles with drug were the two prerequisites for this active loading method. The extended retention capacity of ML has been verified through the prolonged half-life, reduced paw-lick responses in rats, and enhanced tumor inhibition in model mice. In conclusion, ASL-ML prepared by active loading method can effectively load drug into micelles with expected structure and improve drug retention.
- Subjects :
- Amsacrine administration & dosage
Amsacrine analogs & derivatives
Amsacrine pharmacokinetics
Animals
Antineoplastic Agents pharmacokinetics
Dose-Response Relationship, Drug
Female
Liposomes
Male
Mice
Mice, Inbred BALB C
Rats
Rats, Sprague-Dawley
Surface-Active Agents pharmacokinetics
Treatment Outcome
Tumor Burden physiology
Antineoplastic Agents administration & dosage
Drug Delivery Systems methods
Micelles
Surface-Active Agents administration & dosage
Tumor Burden drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0464
- Volume :
- 25
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Drug delivery
- Publication Type :
- Academic Journal
- Accession number :
- 29493300
- Full Text :
- https://doi.org/10.1080/10717544.2018.1440669