AIMTo investigate the biodistribution and the hepatocytes targeting of cationic liposome containing 3beta[N-( N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and surface-modified liposomes with sterylglucoside (SG) and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE).

METHODSCationic liposomes (CL) composed of DC-Chol and dipalmitoylphosphatidylcholine (DPPC), SG/PEG modified cationic liposome (SG/PEG-CL), both contained trace 3H-cholesterol (3H-Chol) as radiolabel, were prepared. The liposomes encapsulating 125I-labled antisense oligodeoxynucleotide (125I-asODN) (SG/PEG-CL-asODN) were also prepared. The biodistribution of CL, SG/PEG-CL, SG/PEG-C2-asODN as well as 125I-asODN solution, were studied. The radioactivities in hepatocytes and non-hepatocytes after administration of CL and SG/PEG-CL were determined by infuseing method.

RESULTSCL and SG/PEG CL significantly aggregated in liver. The distribution of SG/PEG CL was significantly higher in hepatocytes (P < 0.01) and lower in non-hepatocytes (P < 0.01) than that of CL. The concentrations of SG/PEG-CL-asODN in liver and spleen were significantly higher than that of asODN solution (P < 0.01).

CONCLUSIONCationic liposome modified with SG/PEG changed the distribution of asODN. Cationic liposome can target hepatocytes more effective after being modified with SG.

1,2-Dipalmitoylphosphatidylcholine ; administration & dosage ; pharmacokinetics ; Animals ; Area Under Curve ; Cholestenes ; administration & dosage ; pharmacokinetics ; Cholesterol ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Hepatocytes ; metabolism ; Liposomes ; administration & dosage ; pharmacokinetics ; Male ; Mice ; Oligodeoxyribonucleotides, Antisense ; administration & dosage ; pharmacokinetics ; Phosphatidylethanolamines ; administration & dosage ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; pharmacokinetics ; Tissue Distribution

PURPOSE: Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties. MATERIALS AND METHODS: A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten(R). RESULTS: The sSP-C PS and Surfacten(R) were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten(R), and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten(R) revealed similar properties. CONCLUSION: In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten(R). Further study is required to evaluate the in vivo efficacy.
1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives ; Adsorption ; Amino Acid Sequence/*genetics ; Animals ; C-Peptide/*chemistry ; Cattle ; Humans ; Infant, Newborn ; Pulmonary Surfactant-Associated Protein C/*chemical synthesis/pharmacology ; Pulmonary Surfactants/*chemical synthesis/pharmacology ; Respiratory Distress Syndrome, Newborn/*drug therapy ; *Surface Properties ; *Surface Tension ; Surface-Active Agents

AIMTo study the membrane stabilization effect and mechanism of cholesteryl hemisuccinate (CHEMS) on dipalmitoylphosphatidylcholine (DPPC) liposomes; Saikosaponin-D (SSD) liposomes were prepared by using CHEMS as a membrane stabilizer and its encapsulation efficiency and hemolytic activity were evaluated.

METHODSDifferential scanning calorimetry (DSC) and calcein release were used to study membrane stabilization effect of CHEMS on DPPC membrane, Fourier transform infrared spectroscopy (FT-IR) was used to study the interacting mechanism of CHEMS with DPPC, sedimentation experiment was done to study the interaction of CHEMS with SSD and hemolytic study was used to evaluate the hemolytic activity of SSD-liposomes with CHEMS as membrane stabilizer.

RESULTSDSC analysis showed that CHEMS and cholesterol (CHOL) could all decrease the Tm value slightly and the deltaH value markedly. CHEMS was more effective than CHOL in decreasing the deltaH value of DPPC membrane. It suggested that CHEMS was more effective in increasing DPPC membrane stability. It was also proved by calcein release study carried out both in PBS and 30% plasma. The findings by FT-IR suggested that CHEMS has both hydrogen bond and electrostatic interaction with the polar head of DPPC. CHEMS did not form insoluble complex (INCOM) with SSD by sedimentation experiment. Stable SSD-liposomes were prepared using DPPC and CHEMS and decreased effectively the hemolytic activity of SSD, SSD-liposomes may be given intravenously at a concentration of 15 microg x mL(-1), while free SSD was forbidden to be given intravenously.

CONCLUSIONCHEMS was more effective than CHOL in increasing DPPC membrane stability, and it could be of great use in the preparation of cholesterol-dependent hemolytic saponins-liposomes. The hemolytic activity of SSD-liposomes was greatly reduced, allowing a possible concentration of 15 microg x mL(-1) to be intravenously administered.

1,2-Dipalmitoylphosphatidylcholine ; administration & dosage ; Animals ; Calorimetry, Differential Scanning ; Cell Membrane ; drug effects ; Cholesterol ; pharmacology ; Cholesterol Esters ; pharmacology ; Drug Carriers ; Fluoresceins ; metabolism ; Hemolysis ; drug effects ; Liposomes ; Oleanolic Acid ; administration & dosage ; analogs & derivatives ; pharmacology ; Rabbits ; Saponins ; administration & dosage ; pharmacology ; Spectroscopy, Fourier Transform Infrared