• 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.

• Bulletin of the Korean Chemical Society
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• v.5 no.4
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• pp.154-158
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• 1984

In order to characterize the permeability of small unilamellar vesicles (SUV), efflux of 6-carboxyfluorescein (6-CF) from the vesicles was monitored spectrophotofluorometrically. Since the entrapped highly quenched 6-CF (200 mM) became fluorescent upon release from the vesicles, the 6-CF could be used as an efflux probe. SUV containing entrapped 6-CF was prepared from egg phosphatidylcholine and separated by gel filtration on Sepharose 4B. Observed change of relative fluorescent intensity with time was sigmoidal. From this curve, the parameter of permeability was determined either by half-time or a released amount per unit time from the initial slope. Half-time of efflux of prepared SUV having 302 ng phospholipid/ml in 10 mM Tris-HCl buffer pH 7.4 was 21.0 min at $37{\circ}C$. Various factors which could affect the half-time were examined including temperature, pH, salt, and vesicle concentration. In particular the effect of vesicle concentration on the efflux revealed that the permeability can be a function of the concentration.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.283-283
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• 1996

The hydrolyzed-lactose milk for the lactase-deficient subject is sweeter than whole milk, and some subjects dislike its taste. To overcome this shortcoming the dried liposomes containing ${\beta}$-galactosidase to digest lactose in milk after drinking were prepared and examined the possible application of this dried liposomes to the lactase-deficient subjects. To improve the stability of conventional liposome suspension, the dried liposomes in the presence of trehalose were prepared by the dehydration-rehydration vesicles method. Small unilamellar vesicles, prepared with egg phosphatidyl cholesterol, and cholesterol, were mixed with ${\beta}$-galactosidase solution and then ;up[jo;ozed. The freeze-dried liposome was rehydrated and centrifuged. The resultant multilamellar vesicles were mixed with trehalose(4g/g lipid) and then lyophilized to produce final dried liposome. Trehalose increased the entrapping efficiency of liposomes by 3 fo1d compared to the liposomes without trehalose (13% vs. 46%).

• Bulletin of the Korean Chemical Society
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• v.11 no.3
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• pp.238-240
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• 1990

$^{31}P${$^1H$} nuclear Overhauser effects (NOEs) have been obtained for complexes formed between apolipoprotein B (apo B) and dipalmytoylphosphatidylcholine (DPPC) vesicles. NOE measurements have been conducted with broad-band irradiation of the entire $^1H$ spectrum in order to identify the proton source of the NOE. In a unilamellar vesicle formed spontaneously upon mixing aqueous suspensions of long-chain phospholipid with small amount of short-chain lecithin, the maximum NOE occurs at the N-methyl proton resonance position of the choline moiety. With addition of cholesterol to vesicles, the position of the NOE maximum shifts further away from the choline methyl frequency. For the ternary apo B-vesicle-cholesterol complex, the position of the maximum NOE lies halfway between those in vesicles with and without cholesterol.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.743-748
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• 2013

The temperature dependence of the partition coefficients of a neuropeptide, substance P (SP), in isotropic acidic bicelles was investigated by using a pulsed field gradient nuclear magnetic resonance diffusion technique. The addition of negatively charged dimyristoylphosphatidylserine to the neutral bicelle changed the SP partitioning a little, which implies that the hydrophobic interaction between the hydrophobic residues of SP and the acyl chains of lipid molecules is the major interaction while the electrostatic interaction is minor in SP binding in a lipid membrane. From the temperature dependence of the partition coefficients, thermodynamic functions were calculated. The partitioning of SP into the acidic bicelles is enthalpy-driven, as it is for small unilamellar vesicles and dodecylphosphocholine micelles, while peptide partitioning into a large unilamellar vesicle is entropy-driven. This may mean that the size of lipid membranes is a more important factor for peptide binding than the surface curvature and surface charge density.

• 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.

• 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.

• Journal of the Korean Chemical Society
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• v.47 no.5
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• pp.466-471
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• 2003

The effect of polyamines on the cabbage phospholipase D(PLD) activity was investigated. The PLD activity was determined by pH-stat titration of phosphatidic acid, one of the enzymatic reaction product, using phosphatidyl choline small unilamellar vesicles as a substrate. The cabbage PLD was activated approximately 4 fold by spermine at 1 mM concentration. This spermine effect appears to be similar to the previous report on the PLD activation of rat brain mitochondrial fraction. It was also found that cationic polypetides such as polylysine and polyhistidine exerted a marked enhancement effect on the cabbage PLD. Particularly polyhistidine exerted approximately 5.5 fold enhancement effect at 0.062 mM concentration. The polyamine effect on the cabbage PLD was reexamined in the phosphatidylcholine/sodium dodecyl sulfate mixed micellar system. The relevance of polyamine effect on PLD activity is discussed in relation to the active site of PLD.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.17-34
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• 1992

A novel drug delivery system, detergent-phospholipid mixed micelles as proliposomes, for water-insoluble compounds was developed by investigating (i) spontaneous formation of small unilamellar vesicles (SUV) from bile salt-egg phosphatidylcholine mixed micelles, (ii) the molecular mechanism of micelle-to-vesicle transition in aqueous mixtures of detergent-phospholipid, (iii) preparation and screening of a suitable liposomal formulation for a lipophilic drug: solubilization of the drug within the lipid bilayer, evaluation of the solubility limit, and characterization of the resulting product with respect to the physical properties and stability of the drug in the system, and (iv) testing antitumor activity in vitro. The results showed that the new carrier had a strong possibility to be a biocompatible universal formulation for water-insoluble drugs.

• Preventive Nutrition and Food Science
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• v.5 no.2
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• pp.81-85
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• 2000

Bromelain has been used as a meat-tenderizing agent in food processing. To increase the availability of bromelain, microencapsulation into liposome was carried out by the dehydration and rehydration method. Small unilamellar vesicles prepared by sonication treatment showed higher encapsulation efficiency (EE) than by the French press method. In the preparation of liposome, the effect of pH and centrifugal force on EE was also investigated and it showed a higher EE at acidic pH than at alkaline pH with centrifugation at 80, 000$\times$g. The actual EEs except unencapsulated bromelain which bound on the outside surface of liposome by electrostatic interaction also were investigated, and the optimal EE was at pH 4.6, at 0.6 of a ratio of bromelain to phosholipid(18.2%, w/w). Release of bromelain from liposomes was stimulated as the temperature increased at neutral pH.