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| Content Provider | Springer Nature Link |
|---|---|
| Author | Wang, Yongzhong Ding, Yunfei Liu, Ziming Liu, Xingrong Chen, Li Yan, Weili |
| Copyright Year | 2013 |
| Abstract | Construction of a novel PEGylated bioactive lipids-based micelle system for co-delivery of doxorubicin (DOX) and short chain ceramide (C6-ceramide) to overcome multidrug resistance in leukemia.The PEGylated bioactive lipids-based micelle system was constructed via electrostatic and hydrophobic interactions among DOX, bioactive lipids PazPC and C6-ceramide. The micellar formulation was characterized in terms of size, zeta potential, stability and release behavior, etc., and in vitro cytotoxicity, in vivo antitumor efficacy and the underlying mechanism were further evaluated.This novel micellar system showed small size (~15 nm), high drug encapsulation efficiency (>90%), good stability and endosomal acid-triggered release of DOX. Synergistic cytotoxic effects between DOX and bioactive lipid C6-ceramide in P-gp overexpressing drug resistant leukemia P388/ADR cells were observed. The mechanistic studies demonstrated that modulation of drug efflux system and induction of apoptotic effects by lipids were responsible for the synergistic effects between DOX and C6-ceramide in drug resistant leukemia P388/ADR cells. Using an in-vivo P388/ADR leukemia mouse model, the median survival time of the DOX-loaded PEGylated micelles with PazPC and C6-ceramide as major components was significantly greater than that of free DOX and control group.We developed a novel pH sensitive bioactive lipids-based micellar formulation which could potentially be useful in delivering chemotherapeutic drug DOX and provide a novel strategy to increase the therapeutic index for drug resistant leukemia treatment. |
| Starting Page | 2902 |
| Ending Page | 2916 |
| Page Count | 15 |
| File Format | |
| ISSN | 07248741 |
| Journal | Pharmaceutical Research |
| Volume Number | 30 |
| Issue Number | 11 |
| e-ISSN | 1573904X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2013-06-21 |
| Publisher Place | Boston |
| 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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