• 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.28 no.1
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• pp.99-102
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• 2007

To prepare freeze-dried ascorbyl palmitate (AsP)-containing liposome which can protect the drug from moisture attack and be used instantly by mixing with water for anti-aging and skin whitening therapy, AsP was encapsulated into liposomes and freeze-dried with trehalose. The freeze-dried liposome formulations were characterized by measuring water contents, particle size, time required for complete reconstitution. With the freeze-dried liposomes, we performed the stability test under accelerated conditions, skin permeation and localization test. The measurement of the time to perfect reconstitution showed that the freeze-dried liposomes can be changed to their initial state rapidly and short term stability test of AsP in reconstituted liposomes under accelerated conditions confirmed that the stability of AsP was considerably enhanced as compared to freshly prepared liposomes. The skin permeation and localization properties of AsP in reconstituted liposomes were not significantly different, indicating that the liposomal structures were maintained before and after freezedrying. In conclusion, the freeze-drying method provided a possible way to overcome the instability issue of AsP induced by the moisture and reproduced similar skin permeation and localization properties as shown by freshly prepared liposomes.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.249-264
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• 1995

Although liposome has many advantages as a pharmaceutical dosage form, its application in the industrial field has been limited because of some problems such as preparation method, reproducibility, scale-up, stability and sterilization etc. Liposomes prepared by microemulsification method had defined size, narrow size distribution, reproducibility and high entrapment efficiency. For enhancing the stability, the dry form of liposome was recommended. These types of liposome are proliposome and freeze-dried liposome. The liposome must have some properties for preparing of freeze-dried liposome; small size $(50{\sim}200\;nm)$, narrow size distribution and cryoprotectant. In this experiment, the liposomes containing 5-Fluorouracil(5-FU) and its prodrug(pentyl-5-FU-1-acetate; PFA, hexyl-5-FU-1-acetate; HFA) were made with soybean phosphatidylcholine, cholesterol, stearylamine(SA) and dicetyl phosphate(DCP) employing hydration method or microemulsification method using $Microfluidizer^{TM}$. Both or liposome types were MLV and MEL. After preparation, freeze drying and rehydration were performed. In the process of freezing, trehalose(Tr) was added as a cryoprotectant. Their evaluation methods were as follows; entrapment efficiency, mean particle size and size distribution, dissolution test, retain of entrapment efficiency and turbidity after freeze-drying. The results are summarized as belows. The entrapment efficiency of 5-FU was dependent on total lipid concentration and cholesterol content but that of PFA and HFA was decreased when cholesterol was added. When DCP and SA were added, entrapment efficiency was decreased. As the partition coefficient of drug was increased, entrapment efficiency was increased. Under the same condition, entrapment efficiency of MEL is similar to that of MLV. The mean particle size and size distribution of MEL were smaller than those of MLV. Dissolution rates of drug from both liposome types were comparatively similar. Dissolution rates of drugs with serum and liver homogenate were faster than without these material. After preparation of liposome, free drug was removed efficiency by Dowex 50W-X4. When liposome was freeze-dried and then rehydrated in the presence of Tr, characteristics of liposome were maintained well in MEL than MLV. Tr Was used successfully as a cryoprotectant in the process of freeze drying and the optimal ratio of Tr:Lipid was 4:1(g/g).

• YAKHAK HOEJI
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• v.42 no.3
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• pp.274-274
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• 1998

Aclarubicin(ACL)-entrapped freeze dried liposomes were prepared using Microfludizer to attain a sustained release at targeted organs in a prolonged time so that it can reduce th e side effect and maximize the therapeutic effect. The freeze-dried liposomes were evaluated for pharmacokinetics, antitumor activity against Sarcoma 180, cytotoxicity against L1210 and A549 tumor cells, spleen toxicity and myelosuppressive action. The AUC0->8hr values were 122+/-42, 382+/-140, 419+/-171, 835+/-206 and 443+/-309mcg min/ml for free ACL. ACL-liposome formulation I, II, III and IV, respectively. Cytotoidcity of ACL-entrapped liposomes against L1210 and A549 tumor cells was 2-4 times higher than that of free aclarubicin. ACL-liposome formulation I(PC/CHOL/TA) showed the most potent antitumor activity against Sarcoma 180 in mice. The loss of body weight was much smaller with ACL-entrapped liposomes than free ACL after I.p. injection at a dose of 2 mg/kg/day. Compared to free ACL, ACL-entrapped liposomes expressed a lower and delayed spleen toxicity up to 5th day after I.v. administration. Myelosupperssion seemed to be lower with ACL-entrapped liposome of PC/PC-hydrate/CHOL/TA (formulation III) than free aclarubicin.

• Journal of the Korean Chemical Society
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• v.48 no.6
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• pp.616-622
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• 2004

Liposome powders were prepared by a freeze-drying method for the application to the field of drug carrier. The effect of maltose as a liposome stabilizer was studied on the stability and the drug-loading efficiency of the freeze-dried liposome powders. The particle size of liposomes before and after freeze-drying was determined to evaluate the liposome stability. The drug-loading efficiency was measured by Fluorescence spectrophotometer using calcein as a model drug. When maltose was added after the preparation of the liposomes, the liposomes was stable, compared to the case of maltose addition at the hydration procedure. By the addition of maltose, the liposome was stable for 30 days at $4{\sim}37^{\circ}C$, while the particle size of the liposome without maltose increased with time. The liposome showed relatively high stability when the maltose/lipids molar ratio was 3 and 6.

• YAKHAK HOEJI
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• v.42 no.3
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• pp.275-283
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• 1998

Aclarubicin(ACL)-entrapped freeze dried liposomes were prepared using Microfludizer to attain a sustained release at targeted organs in a prolonged time so that it can reduce th e side effect and maximize the therapeutic effect. The freeze-dried liposomes were evaluated for pharmacokinetics, antitumor activity against Sarcoma 180, cytotoxicity against L1210 and A549 tumor cells, spleen toxicity and myelosuppressive action. The $AUC_{0{\rightarrow}8hr}$ values were $122{\pm}42,\;382{\pm}140,\;419{\pm}171,\;835{\pm}206\;and\;443{\pm}309{\mu}g{\cdot}min/ml$ for free ACL. ACL-liposome formulation I, II, III and IV, respectively. Cytotoidcity of ACL-entrapped liposomes against L1210 and A549 tumor cells was 2-4 times higher than that of free aclarubicin. ACL-liposome formulation I(PC/CHOL/TA) showed the most potent antitumor activity against Sarcoma 180 in mice. The loss of body weight was much smaller with ACL-entrapped liposomes than free ACL after I.p. injection at a dose of 2 mg/kg/day. Compared to free ACL, ACL-entrapped liposomes expressed a lower and delayed spleen toxicity up to 5th day after I.v. administration. Myelosupperssion seemed to be lower with ACL-entrapped liposome of PC/PC-hydrate/CHOL/TA (formulation III) than free aclarubicin.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.646-652
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• 1996

Epidermal Growth Factor (EGF), discovered by Stanley Cohen in 1960, has a potential healing effect for wounds and bums. Considering wound care, in order to avoid physical stress at the wound surface and efficiently apply EGF, the need for viscous spraying solutions was essential. Viscous spraying solutions containing EGF were prepared by utilizing viscosity-building polymer, poloxamer 407, and by introducing liposome systems. On the other hand, EGF is purified on reverse HPLC gradient program with the mobile solvent of acetonitrile. It is necessary to observe liposomal EGF changes as the acetonitrile contents varied in order to introduce liposome systems at the step of EGF solution (at the time of EGF purifying). By evaluating the size distribution and entrapment efficiency of EGF liposome, it was possible to detemine the limit contents of acetonitrile and establish the optimal conditions for solution formulations. It has been revealed that, as the acetonitrile content increases, mean diameter of EGF liposomes increased and the width of size distribution tends to decrease. The limit contents of acetonitrile were 10%, since there was little difference to the acetonitrile free liposomes.

• The Korean Journal of Nuclear Medicine
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• v.36 no.6
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• pp.333-343
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• 2002

Purpose: A new linker, hydrazino nicotinamide (HYNIC), was recently introduced for labelling of liposome with $^{99m}Tc$. In this study we synthesized HYNIC derivatized PEG (polyethylene glycol)-liposomes radiolabeled with $^{99m}Tc$. Materials and Methods: In order to synthesize HYNIC-DSPE (distearoyl phosphatidyl ethanolamine) which is a crucial component for $^{99m}Tc$ chelation, first of all succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized from 6-chloronicotinic acid by three sequential reactions. A DSPE derivative of succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was transformed into HYNIC-DSPE by HCI/dioxane. HYNIC-PEG-liposomes were prepared by hydration of the dried lipid mixture of EPC (egg phosphatidyl choline): PEG-DSPE : HYNIC-DSPE:cholesterol (1.85:0.15:0.07:1, molar ratio). The HYNIC-PEG-liposomes were labeled with $^{99m}Tc$ in the presence of $SnCl_2{\cdot}2H_2O$ (a reducing agent) and tricine (a coligand). To investigate the level of in vivo transchelation of $^{99m}Tc$ in the liposomes, the $^{99m}Tc$-HYNiC-PES-liposomes were incubated with a molar excess of DTPA, cysteine or glutathione solutions at $37^{\circ}C$ for 1 hour. The radiolabeled liposomes were also incubated in the presence of human serum at $37^{\circ}C$ for 24 hours. Results: 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized with 77.3% overall yield. The HYNIC concentration in the PEG-coated liposome dispersion was 1.08 mM. In condition of considering the measured liposomal size of 106 nm, the phospholipid concentration of $77.5\;{\mu}mol/m{\ell}$ and the liposomal particle number of $5.2{\times}10^{14}$ liposomes/ml, it is corresponded to approximate 1,250 nicotinyl hydrazine group per liposome in HYNIC-PEG-liposome. The removal of free $^{99m}Tc$ was not necessary because the labeling efficiency were above 99%. The radiolabeled liposomes maintained 98%, 96% and 99%, respectively, of radioactivity after incubation with transchelators. The radiolabeled liposomes possessed above 90% of the radioactivity in serum. Conclusion: These results suggest that the HYNIC can be synthesized easily and applied in labelling of PEG-liposomes with $^{99m}Tc$.