• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.85-90
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• 2010

Docetaxel-loaded liposomes were prepared by emulsion-solvent evaporation method, then coated with chitosan at room temperature and lyophilized. This system was designed in order to improve solubility and stability of docetaxel in the GI tract for oral drug delivery. The solubilizing effect of some frequently used solubilizers and/or liposome was determined. Among the results docetaxel-loaded liposomes prepared with 0.5% TPGS as a solubilizer showed 100-fold higher solubility than docetaxel. In a stability test, mean particle size of different liposome formulations was measured by a particle size analyzer in simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). The particle size of uncoated liposomes was significantly increased compared with that of chitosan-coated liposomes in SGF, however, there was no significant difference between coated and uncoated liposome in SIF. It is evident that chitosan-coated liposomes were more stable in GI conditions. The release characteristics of docetaxel-loaded liposomes were also investigated in three buffer solutions (pH 1.2, 4.0, 6.8). Docetaxel release did not occur in pH 1.2 for 4 hrs. However, in pH 4.0 and 6.8 conditions, docetaxel was gradually released over 24 hrs as a sustained release. It seems that aggregation and precipitation of particles by electrostatic interaction might protect docetaxel from being released. In Conclusion, the results from this study show that the chitosan-coated liposomes may be useful in enhancing solubility and GI stability of docetaxel.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.299-304
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• 2006

The aim of this study was to investigate the effect of deformable liposomes with sodium cholate on the skin permeation and skin deposition of arbutin, a hydrophilic skin-whitening agent. Various compositions of liposomes were prepared by the extrusion method. Particle size distribution and entrapment efficiency were determined by the laser light scattering and the gel permeation chromatography, respectively. The in vitro rat skin permeation and deposition of arbutin in various skin layers were investigated using the Keshary-Chien diffusion cells at $37^{\circ}C$. The average particle size of the deformable liposomes ranged from 217.4 to 117.4 nm, depending on the composition. The entrapment efficiency was dependent on surfactant concentration and loading dose of arbutin. The permeation rate of 5% arbutin in deformable liposomes was $8.91({\pm}1.33){\mu}g/cm^2/h$, and was not significantly different from 5% arbutin aqueous solution $[9.82({\m}0.86){\mu}g/cm^2/h]$. The deposition of arbutin was $43.34({\pm}12.13)$ and $16.99({\pm}7.83){\mu}g/cm^2$ in stratum corneum layer and epidermis/dermis layer, respectively, after 12 h of permeation study. These results are consistent with several earlier studies for the localization effect of liposomal formulations in stratum corneum, and demonstrated the feasibility of the deformable liposomes as a promising carrier for the skin deposition of hydrophilic skin-whitening compounds.

• Journal of the Korean Chemical Society
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• v.51 no.1
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• pp.43-50
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• 2007

Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.

• Applied Chemistry for Engineering
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• v.26 no.2
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• pp.165-172
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• 2015

Quercetin and its glycoside, rutin, are flavonoids, which are well known as natural antioxidants. In this study, cationic liposomes loaded with flavonoids (quercetin or rutin) were investigated for their effects on cell and skin permeability, and protective effects against UVA. The particle size of the empty cationic liposomes was in the range of 100~130 nm, and the zeta potential was + 33.05 mV. The entrapment efficiency of 0.5R/CL was higher than that of 0.5 Q/CL. The cellular uptake of the cationic liposomes was five-fold higher than that of liposomes. The skin permeability of quercetin and rutin was investigated using Franz diffusion cells. Compared to the initial loading dose, the amount of quercetin or rutin delivered to the skin by cationic liposomes was higher than that delivered by conventional liposomes or phosphate-buffered saline. From the protective effect of cationic liposomes against UVA ($25J/cm^2$), we found that the cell viability in cationic liposomes containing flavonoids was higher than that of using UVA irradiation only. These results indicate that cationic liposomes provide enhanced delivery of flavonoids (quercetin and rutin) into the skin and may be used for antiaging and antioxidant cosmetics.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.115-124
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• 1992

The characteristics and stabilities of phosphatidylcholine liposomes covalently coupled with immunoglobulin fragments prepared by the REV method were investigated by the dynamic light scattering, absorbance and calcein release. Using a sulfhydryl-reactive phospholipid derivative of N-[4$({\rho}-maleimido-phenyl)$ butyl] phosphatidylethanolamine (MPB-PE), Fab' antibody fragments were covalently combined with preformed large unilamellar vesicles (LUV), Coupling ratio was $250\;{\mu}g$ of $Fab'/{\mu}mol$ of phospholipid in vesicles, From dynamic light scattering, it was found that the size of the vesicles increases as the ratio of cholesterol to lipid increases, but that apparently, the size of liposomes was not sensitive to the existence of Fab' fragments. Regardless of inserting Fab' fragments, the absorbance of liposomes decreased as the amounts of bile salt (BS) added. At very low BS concentrations, BS/lipid aggregates would be formed in the outer vesicles monolayer, while, at the high BS concentrations, mixed micelles would be preferred. The vesicles incorporated with Fab' fragments, however, are more resistant to the bile salts than the MPB-PE vesicle are. The absorbance of vacant liposomes and calcein release resulted in that the Fab' vesicles and MPB-PE vesicles by the REV method are very stable, but that those by the sonication method sufferred the significant change of turbidities.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.6
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• pp.516-521
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• 2005

Drug delivery to the lymphatic system may be important in terms of the treatment with lymphatic involvement, such as tumor metastases and immunization. Especially, drug transport via the intestinal lymphatics after oral administration has been attracted lots of interests. The purpose of this study was to prepare cyclosporin A (CSA)-loaded liposomes, with different characteristics, and evaluate their mucoadhesivity. Three liposome preparations were formulated: cationic stearylamine liposomes (SA-Lip), anionic phosphatidylserine liposomes (PS-Lip), Polymer (chitosan)-coated liposomes (CS-Lip), and characterized. The liposome preparations were found to be spherical in shape, with PS-Lip being the smallest. The liposome preparations exhibited entrapment efficiencies in the order: PS-Lip $(52.5{\pm}2.9%)$ > SA-Lip $(48.8{\pm}3.3%)$ > CS-Lip $(41.7{\pm}4.2%)$. Finally, mucoadhesive tests were carried out using rat intestine, with SA-Lip (67%) showing the best adhesive rate of the three preparations (PS-Lip: 56%, CS-Lip: 61%). These results suggest that a positive charge on the surface of drug carriers may be an important factor for the intestinal drug delivery.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.319-329
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• 2003

Ursolic acid (UA) and oleanolic acid (OA) are pentacyclic triterpenoids which are widely distributed in plants, and their derivatives are aglycones of many naturally occurring saponins. It is known that pentacyclic acids may possibly enhance the mechanical barrier functions of cell membranes in plants. Recently, it has been reported that OA and UA have interesting biological activities on skin, such as anti-inflammatory and anti-wrinkle activities. Since triterpenoids are extremely insoluble and their solubility problem limits skin-care application, OA and UA were encapsulated in liposomes via micelle-to-vesicle transition to overcome poorly soluble property and enhance biological efficacy. Optimal molar ratio of OA to lecithin was found to exist for producing liposomes of small hydrodynamic size and liposomal suspensions without recrystallized precipitation of OA. From electron micrograph and dynamic light scattering studies, reconstituted OA-containing liposomes without severe mechanical treatment showed small hydrodynamic size about 150 nm. Wide-angle X-ray diffraction coupled with dynamic light scattering revealed that optimal amount of OA in liposome was 25.4 mole %. In biological evaluation, OA-containing liposome significantly increased filaggrin and transglutaminase as markers of keratinocyte differentiation in epidermal layer of hairless mouse, whereas ursolic acid-containing liposome did not show noticeable increase of filaggrin and transglutaminase compared to empty liposome. It is concluded that nano-scaled liposomes containing triterpenoids were spontaneously prepared by vesicular transition from mixed micelle and liposomal triterpenoids can enhance skin absorption of triterpenoid and biological efficacy.

• 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 $^{99m}Tc$.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.300.2-300.2
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• 2003

Unlike cationic liposome/DNA complexes, neutralliposomes containing plasmid DNA are stable in blood and does not selectively entrapped in the lung. The objective of this study was to construct neutral liposomes containing plasmid DNA with optimal encapsulation efficiency. Plasmid DNA (pGL2 clone 753,-6 kb) was encapsulated by the freeze/thawing method into liposomes composed of 1-palmitoyl-2-oleyl-sn-glycerol-3-phosphocholine(POPC), didodecyldimethylammonium bromide(DDAB), distaroylphosphatidyl-ethanolamine polyethylene glycol 2000(DSPE-PEG 2000) and DSPE-PEG 2000-maleimide. (omitted)

• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.319-323
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• 2008

For transdermal delivery of ceramides, various liposomes formulations were studied and evaluated. Sodium deoxycholate (SDC), Tween 20 and Span 85 were used as edge activators. The skin permeation of ceramides was performed using a Franz cell apparatus with hairless mouse skin. Among edge activators, SDC showed the higher values of deformability index and skin permeation than did others. For optimization of formulations, we varied the ratios of lipids to edge activators and the compositions between phosphatidylcholine (PC) and ceramides. The optimal ratio of lipid to SDC was observed to be 6:1 (w:w) and that of PC and ceramide was 1:1. Our results suggest that the skin permeation of ceramides could be enhanced by optimized deformable formulations of liposomes containing SDC as a major edge activator.