Role of copper gluconate/triethanolamine in irinotecan encapsulation inside the liposomes.
A novel method for encapsulating irinotecan into liposomes containing copper gluconate buffered to pH 7.0 with triethanolamine (TEA) has recently been developed. In the present study, the mechanism dictating drug encapsulation and retention inside those liposomes was investigated. Spectroscopic analyses revealed that irinotecan interacted with copper gluconate/TEA in solution. Fourier transformed infrared (FT-IR) spectroscopy indicated a strengthening of the hydrogen bonds involving the hydroxyl groups when solutions of irinotecan and copper gluconate/TEA are mixed at a 1:1 molar ratio. The intensity of the circular dichroism (CD) signal of copper gluconate/TEA increased in the presence of equimolar amounts of irinotecan. The addition of irinotecan to liposomes containing copper gluconate/TEA at 50 degrees C induced a shift of the absorption bands from 370 nm to 378 nm as well as a 60% quenching of the drug fluorescence at 440 nm suggesting the occurrence of irinotecan self association. Irinotecan encapsulation was found to be kinetically and stoichiometrically correlated with the release of TEA from the liposomes. The results suggested that the encapsulation of irinotecan was mediated by TEA in association with copper gluconate, leading to a final drug complex that is retained inside the liposomes. A neutral antiport exchange loading mechanism between irinotecan and TEA is proposed.
Dicko
Awa
A
Celator Pharmaceuticals Corp., 1779 W 75th Avenue, Vancouver, BC V6P 6P2, Canada.
Tardi
Paul
P
Xie
Xiaowei
X
Mayer
Lawrence
L
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D004339:Drug Compounding; D004983:Ethanolamines / Q000737:chemistry*; D005942:Gluconates / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D000077146:Irinotecan; D007700:Kinetics; D008081:Liposomes; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
D000972:Antineoplastic Agents, Phytogenic; D004983:Ethanolamines; D005942:Gluconates; D008081:Liposomes; D000077146:Irinotecan; C009546:triethanolamine; D002166:Camptothecin