title: Comparative studies of irinotecan-loaded polyethylene glycol-modified liposomes prepared using different PEG-modification methods.
abstract: Recently, a polyethylene glycol (PEG)-modification method for liposomes prepared using pH-gradient method has been proposed. The differences in the pharmacokinetics and the impact on the antitumor effect were examined; however the impact of PEG-lipid molar weight has not been investigated yet. The main purpose of this study is to evaluate the impact of PEG-lipid molar weight against the differences in the pharmacokinetics, the drug-release profile, and the antitumor effect between the proposed PEG-modification method, called the post-modification method, and the conventional PEG-modification method, called the pre-modification method. Various comparative studies were performed using irinotecan as a general model drug. The results showed that PEG-lipid degradation could be markedly inhibited in the post-modification method. Furthermore, prolonged circulation time was observed in the post-modification method. The sustained drug-release was observed in the post-modification method by the results of the drug-releasing test in plasma. Moreover, a higher antitumor effect was observed in the post-modification method. It was also confirmed that the same behaviors were observed in all comparative studies even though the PEG molecular weight was lower. In conclusion, the post-modification method has the potential to be a valuable PEG-modification method that can achieve higher preservation stability of PEG-lipid, prolonged circulation time, and higher antitumor effect with only half the amount of PEG-lipid as compared to the pre-modification method. Furthermore, it was demonstrated that PEG(5000)-lipid would be more desirable than PEG(2000)-lipid since it requires much smaller amount of PEG-lipid to demonstrate the same performances.
authors: Terumo Corporation, R&D Center, Ashigarakami-gun, Kanagawa, Japan. Keisuke_Yoshino@terumo.co.jp
authors: Keisuke
authors: K
authors: Yoshino
authors: Koji
authors: K
authors: Nakamura
authors: Yoko
authors: Y
authors: Terajima
authors: Akinobu
authors: A
authors: Kurita
authors: Takeshi
authors: T
authors: Matsuzaki
authors: Keiko
authors: K
authors: Yamashita
authors: Masashi
authors: M
authors: Isozaki
authors: Hiroaki
authors: H
authors: Kasukawa
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D008081:Liposomes; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin