Stability and antitumor effects of all-trans retinoic acid-loaded liposomes contained sterylglucoside mixture.
The aim of this study was to develop an intravenous delivery of all-trans retinoic acid (ATRA) for the treatment of cancer. Two kinds of liposomes composed of dipalmitoylphosphatidylcholine and cholesterol with sterylglucoside (SG) mixture (SG liposomes) or without SG (non-SG liposomes) were prepared. A limited amount of ATRA was incorporated into liposomes approximately 3mol%. ATRA-loaded SG liposomes were more stable at 4 degrees C with light protection for 24 days than non-SG liposomes; maintaining 83.1% ATRA and the average diameter 198.5 nm (36 days), and in 80% rat serum for 120 min. SG seems to increase the ATRA-loaded efficiency in liposomes and stability of liposomes compared with cholesterol. The mean survival time of mice given SG liposomes (18.2 days) indicated a greater antitumor activity than saline (14.1 days) (P<0.001) without change of mean body weight. It is concluded that the current ATRA-loaded SG liposomes are potentially applicable for hepatic metastasis of M5076 tumor.
Shimizu
Kazuyuki
K
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa-ku, 142, Tokyo, Japan.
Tamagawa
Kayoko
K
Takahashi
Noriko
N
Takayama
Kozo
K
Maitani
Yoshie
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002782:Cholestenes / Q000008:administration & dosage / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D007275:Injections, Intravenous; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000556:secondary; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D014212:Tretinoin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use
D000970:Antineoplastic Agents; D002782:Cholestenes; D004337:Drug Carriers; D008081:Liposomes; C096056:soy derived sterylglucoside mixture; D014212:Tretinoin