Sustained release of hydroxycamptothecin after subcutaneous administration using a novel phospholipid complex-DepoFoam technology.
OBJECTIVE
In order to prolong the duration of drug in the circulation, multivesicular liposome (MVL, namely DepoFoam) was utilized as a sustained-release delivery system for hydroxycamptothecin (HCPT).


METHODS
HCPT is insoluble in both water and physiological acceptable organic solvents; therefore, HCPT-phospholipid complex (HCPT-PCC) was prepared by solvent evaporation method to improve its liposolubility. In this study, preparation, characterization, in vitro release, and in vivo pharmacokinetics of HCPT-phospholipid complex-loaded MVLs (HCPT-MVLs) were investigated.


RESULTS
The results showed that the average particle size of HCPT-MVL was 9 mum and the encapsulation efficiency was 90%. In addition, HCPT-MVLs could improve both in vitro release and in vivo pharmacokinetic behaviors of the original drug, with a sustained release of drugs over 5-6 days.


CONCLUSIONS
These data suggested that by combined use of DepoFoam and phospholipid complex formation technique HCPT could be successfully entrapped into the MVLs, which might provide a paradigm for sustained release of insoluble drugs.
Zhao
Yue
Y
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan, PR China.
Liu
Jie
J
Sun
Xun
X
Zhang
Zhi-Rong
ZR
Gong
Tao
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D007279:Injections, Subcutaneous; D008081:Liposomes; D010316:Particle Size; D010743:Phospholipids; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D010743:Phospholipids; C527042:hydroxycamptothecinum; D002166:Camptothecin