چکیده (انگلیسی):

The purpose of this study was to establish a new experimental
approach to determine the maximum amount of camptothecin
(CPT) that can be incorporated in liposomes, and to use this
method to compare the CPT-incorporation capacity of various
liposome formulations. Small, CPT-saturated liposomes were
prepared by dispersing freeze-dried blends of lipids and drug in
phosphate buffer, and subsequent probe-sonication. Excess precipitated
CPT could be separated from the liposomes by ultracentrifugation.
The small and homogeneous liposome size
obtained gave a good and reproducible recovery of liposomes
in the supernatant (>80%), whereas the acidic pH (pH 6.0) kept
CPT in its hydrophobic lactone form, which is poorly soluble
in the buffer. The maximum CPT-incorporation capacity of 12
different liposome formulations was investigated, using the
described method, and was found to vary widely. With liposomes
made of neutral and anionic phospholipids, the solubility
of CPT in the buffer was improved by approximately a factor
of 10 (from ~2.7 to 15-50 μg/mL) as compared with buffer.
With cationic liposomes containing 1,2-dioleoyl-3-trimethylammonium-
propane (DOTAP), a maximum CPT-solubilization
of ~100-fold, the buffer solubility was reached, probably
owing to an electrostatic interaction between the cationic lipids
and the carboxylate-CPT isomer. Increasing DOTAP fractions
within egg-phosphatidylcholine (EPC)/DOTAP liposomes
reached a CPT-incorporation plateau at ~20 mol% DOTAP.
The presented approach appears suitable to study the incorporation
capacity of any drug component within small vesicles as
long as the liposome incorporation is high relative to the intrinsic
water solubility of the drug.