Characterization and pharmacokinetics of a novel pirarubicin liposome powder.
BACKGROUND
Pirarubicin (THP), an analogue of doxorubicin, has exhibited promising activities against acute leukemia, malignant lymphoma, and several solid tumors. However, the cumulative cardiotoxicity limits its wide application in chemotherapy.


METHODS
To provide an alternative strategy for reducing the cardiotoxicity, a novel THP liposome powder (L-THP), comprising distearoylphosphatidylcholine, distearoylphosphatidylglycerol, cholesterol, and lactose was appropriately prepared based on the physicochemical properties of THP. And L-THP was characterized and evaluated. Comparative studies on pharmacokinetic and biodistribution behaviors between L-THP and commercialized THP injection were performed in normal mice through intravenous administration.


RESULTS
When L-THP was reconstituted in a proper amount of normal saline for injection, it had a mean diameter of around 220.0 nm, a zeta potential of about -33.0 mV, and a high THP entrapment efficiency of more than 93.1%. Pharmacokinetics study showed that heart accumulation of THP could be reduced by 81.2% for L-THP.


CONCLUSIONS
These results suggest that our L-THP might greatly reduce the cardiotoxicity, thus improving the therapeutic index of THP. Meanwhile, further preclinical studies are warranted to define the cardiotoxicity and the therapeutic efficacy of L-THP.
Cong
Wenjuan
W
School of Pharmacy, East China University of Science and Technology, Shanghai, PR China.
Liu
Qingfei
Q
Chen
Xi
X
Gao
Rong
R
Lu
Juan
J
Wang
Yiming
Y
Luo
Guoan
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers; D004355:Drug Stability; D005079:Excipients; D008081:Liposomes; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D011208:Powders; D012995:Solubility; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D011208:Powders; D004317:Doxorubicin; C027260:pirarubicin