• Archives of Pharmacal Research
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• v.10 no.2
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• pp.75-79
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• 1987

Liposomes were studied as a drug delivery system. Multilamellar vesicles, small unilamellar vesicles and large unilamellar vesicles containing cytarabine were prepared using egg yolk lecithin and cholesterol. Large unilamellar vesicles showed the highest encapsulation efficiency of all and their encapsulation efficiency increased as the buffer volume decreased. Cholesterol increased the stability of liposomal drug products as drug carriers and reduced the permeability of drug across the liposomal membrane. The release rate of cytarabine increased with incubation temperature and decreased with cholesterol incorporation in liposomal membrane. The release mechanism of cytarabine from large unilamellar vesicles in vitro was chiefly due to simple diffusion across the liposomal membrane rather than liposomal rupture.

• YAKHAK HOEJI
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• v.38 no.6
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• pp.637-645
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• 1994

The effect of various drugs on the stability of the liposomal membrane of phosphatidylcholine and cholesterol was studied, employing the fluorescence self-quenching method. Calcein was entrapped into the phospholipid small unilamellar vesicles and the leakage of the fluorescence probe was monitored on adding the drug to the system. The results of the experiments showed that phenothiazine derivatives, some potent local anesthetics and surface active agents were very effective in inducing the leakage of calcein from the liposome. The leakage-inducing activity of these drug substances has been ascribed to their surface activity and the perturbation of the liposomal membrane by these substances. On the other hand drug substance with low surface activity or without amphiphilic moieties did not show any effect or only small effect on the leakage of calcein from the liposomes. The effect of lipid concentration on the stability of the liposomes was also investigated to show that the higher concentrations of lipid more drug was required to induce the leakage. The effect of surface charges of vesicles was also studied, and the results showed that the charge on the liposomes enhanced the stability of the liposomes against the leakage-inducing activity of these drug substances.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.3
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• pp.508-517
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• 1998

We investigated the effects of godulbaegi extracts on the physiochemical properties of biological membranes as membrane stability and fluidity employing the phospholipid liposomal membrances as a biomembrane-mimetic system. The addition of the godulbaegi extracts to the phospholipid exterted great effects stagbilized the barrier function of the liposomal membranes in proportion to the concentration of the additive and significantly increased the membranes fluidity. The values of the fluorescence polarization of 1,6-diphenyl 1,3,5-hexatriene (DPH) decreased gradually as the temperature increased, and decreased abruptly near the phase transition temperature (Tm) of the liposome from gel to liquid crystalline state as usual. These results suggest that the activities of the godulbaegi extracts to enhance the stability and fluidity of the liposomal membranes have implication in their biological activities.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.3
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• pp.518-524
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• 1998

Liposomes have been widely employed as biomembrane-mimetic system and drug-delivery system. In these applications, the low stability of liposomes has been the most serious problem. They have relatively short half-lives and easily lysed through interactions with biological components. This study was performed to investigate the effects of godulbaegi extracts on the fludity of phospholipid liposomes. We used dipalmitoyl phosphatidylcholine(DPPC) liposomes which make most stable liposomes among the other phosphatidylcholines. The thermograms of the DPPC liposomal bilayers incorporated with the hexane extract of godulbaegi(Ixeris sonchifolia H.) were obtained, and the enthalpy changes and the sizes of cooperative unit of the transition were calculated. The incorporation of the Ixeris sonchifolia H. into the liposomal bilayers effectively reduced the transition temperature at which the transition from gel state to liquid-crystalline state occurs, broadened the thermogram peaks, and reduced the ratio of van't Hoff to calorimetric enthalpies. These results indicate indicate that the godulbaegi extracts (Ixeris sonchifolia H.) have significant effects on the fluidity of biological membrance.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.131-139
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• 1994

Calcein-encapsulated small unilamellar vesicles of various lipid composition were prepared using the sonication technique, and their stabilities at $20^{\circ}C$ were examined by measuring calcein leakage from the liposomes. The fluidity of these liposomal bilayers was also investigated by measuring the fluorescence polarization of DPH labelled into the liposomes. The results showed that liposomes made of PC mixtures with different acyl chain length were very stable, which may be due to the formation of interdigitated bilayer structure. The addition of cholesterol further stabilized these PC liposomes. However, addition of cholesterol reduced the encapsulation efficiences of liposomes. The fluidity of the liposomes was significantly decreased by cholesterol in the liquid crystalline state, but not changed in the gel state. These results suggest that the enhanced stability of PC mixture liposomes may be ascribed to the formation of stable interdigitated bilayer structure. In membrane-mimetic and drug-delivery studies, vesicles made of mixtures of various phospholipids are recommended instead of addition of cholesterol to the phospholipid.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.626-635
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• 2005

Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been reported in attempt to improve the stability and antitumor activity of TPT. However, the biodistr ibution pattern of TPT liposome in vivo and PEG-modified liposome containing TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several liposomes containing TPT with different lipid compositions and PEG-modification were studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S$_{180}$ tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip and H-Lip resulted in 5- and 19- fold increase in the area under the curve (AUC$_{0\rightarrow\propto}$), respectively. PEG- modified H-Lip (H-PEG) showed 3.7-fold increase in AUC$_{0\rightarrow\propto}$ compared with H-Lip, but there was no significant increase in t$_{1/2}$ and AUC$_{0\rightarrow\propto}$ for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the relative tumor uptake ratios were 3.4 and 4.3 compared with free drug, respectively. There was also a marked increase in the distribution of TPT in lung when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of TPT in bore marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of liposome has an important effect on in vitro stability and in vivo biodistribution pattern of liposomes containing TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.