Oxidized phospholipid based pH sensitive micelles for delivery of anthracyclines to resistant leukemia cells in vitro.
A self-assembled micelle drug delivery system was constructed with an oxidized phospholipid for anthracycline anti-cancer drug delivery. An oxidized phospholipid, 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazPC), was chosen to fabricate micelles via both electrostatic and hydrophobic interactions for delivery of doxorubicin (DOX) and idarubicin (IDA). The formation of ion-pair complexes between PazPC and DOX was first investigated under different pH conditions. Drug-loaded PazPC micelles at a 5:1 molar ratio of lipid/drug at pH 7.0 were then prepared by the solvent evaporation method. The empty and drug-loaded PazPC micelles exhibited a small particle size (∼10 nm) and high encapsulation efficiency. In vitro stability and release profile indicated that the micelles were stable at physiological conditions, but exhibited pH-sensitive behavior with accelerated release of DOX or IDA in an acidic endosome environment. Finally, in vitro uptake and cytotoxicity were evaluated for leukemia P388 and its resistant subline P388/ADR. The drug-loaded PazPC micelles enhanced drug uptake and exhibited higher cytotoxicity in both leukemia cells in comparison to free drugs. In conclusion, we developed a novel pH sensitive oxidized phospholipid-based micellar formulation which could potentially be useful in delivering anthracycline anti-cancer drugs and provide a novel strategy for increasing the therapeutic index while overcoming multidrug resistance for leukemia treatment.
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
Yongzhong
Y
Wang
Li
L
Chen
Yunfei
Y
Ding
Weili
W
Yan
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D019008:Drug Resistance, Neoplasm; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D015255:Idarubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008823:Micelles; D010084:Oxidation-Reduction; D010316:Particle Size; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
C528536:1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D012997:Solvents; D010767:Phosphorylcholine; D004317:Doxorubicin; D015255:Idarubicin