Comparative studies of irinotecan-loaded polyethylene glycol-modified liposomes prepared using different PEG-modification methods
| Autor: | Hiroaki Kasukawa, Keisuke Yoshino, Koji Nakamura, Yoko Terajima, Takeshi Matsuzaki, Masashi Isozaki, Akinobu Kurita, Keiko Yamashita |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
PEG-modification method
Prolonged circulation time Biophysics Antineoplastic Agents macromolecular substances Polyethylene glycol Irinotecan Biochemistry Polyethylene Glycols chemistry.chemical_compound Pharmacokinetics PEG ratio medicine Humans Polyethylene glycol (PEG) molar weight Liposome Chromatography Molar mass Antitumor effect technology industry and agriculture Cell Biology chemistry pH-gradient method Liposomes Degradation (geology) Camptothecin HT29 Cells medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1818(11):2901-2907 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/j.bbamem.2012.07.011 |
| Popis: | 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 PEG5000-lipid would be more desirable than PEG2000-lipid since it requires much smaller amount of PEG-lipid to demonstrate the same performances. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect