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.
Hosokawa
Toshihito
T
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., LTD., Sunto-gun, Shizuoka, Japan. t.hosokawa@kyowa.co.jp
Sami
Mari
M
Kato
Yasuki
Y
Hayakawa
Eiji
E
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