Alteration in the temperature-dependent content release property of thermosensitive liposomes in plasma.
The effect of plasma components on the temperature-dependent content release property of thermosensitive liposomes has been described. Temperature-sensitive liposomes containing mitomycin C (MMC) were prepared from dipalmitoylphosphatidylcholine (DPPC liposomes) and a 7 : 3 mixture of DPPC and dipalmitoylophosphatidylglycerol (DPPC/DPPG liposomes). We defined in this study the difference in the content release between 38 degrees C and 44 degrees C as an index of the temperature-dependent content release efficiency (Delta% release). In the absence of rat plasma, the Delta% release of the DPPC liposomes and the DPPC/DPPG liposomes was 83% and 71%, respectively. However, when the release study was conducted with rat plasma, the Delta% release increased to about 96% for both liposomes. In addition, while the DPPC liposomes were destabilized by rat plasma below the gel-to-liquid crystalline phase transition temperature (T(m)), MMC leakage from the DPPC/DPPG liposomes below T(m) was suppressed by rat plasma. Moreover, the plasma protein binding onto lipid bilayer was concomitant with the gel-to-liquid crystalline phase transition and then enhanced the temperature-dependent release from the DPPC/DPPG liposomes. The possible mechanism of interaction between liposomes and plasma proteins, especially serum albumin, was discussed based on differential scanning calorimetry and protein binding experiments.
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., LTD., Sunto-gun, Shizuoka, Japan. t.hosokawa@kyowa.co.jp
Toshihito
T
Hosokawa
Mari
M
Sami
Yasuki
Y
Kato
Eiji
E
Hayakawa
D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D001798:Blood Proteins / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004337:Drug Carriers; D006358:Hot Temperature; D066298:In Vitro Techniques; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes / Q000097:blood* / Q000737:chemistry*; D016685:Mitomycin / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011485:Protein Binding; D051381:Rats; D012995:Solubility; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D001798:Blood Proteins; D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D016685:Mitomycin