The purpose of this study was to provide a basis for studying the molecular mechanism of pharmacological action of chlorhexidine digluconate. Large unilamellar vesicles (OPGTL) were prepared with total lipids extracted from cultured Porphyromonas gingivalis outer membranes (OPG). The anthroyloxy probes were located at a graded series of depths inside a membrane, depending on its substitution position (n) in the aliphatic chain. Fluorescence polarization of n- (9-anthroyloxy)stearic acid was used to examine effects of chlorhexidine digluconate on differential rotational mobility, while changing the probes' substitution position (n) in the membrane phospholipids aliphatic chain. Magnitude of the rotational mobility of the intact six membrane components differed depending on the substitution position in the descending order of 16- (9-anthroyloxy)palmitic acid (16-AP), 12, 9, 6, 3 and 2- (9-anthroyloxy)stearic acid (12-AS, 9-AS, 6-AS, 3-AS and 2-AS). Chlorhexidine digluconate increased in a dose-dependent manner the rate of rotational mobility of hydrocarbon interior of the OPGTL prepared with total lipids extracted from cultured OPG, but decreased the mobility of membrane interface of the OPGTL. Disordering or ordering effects of chlorhexidine digluconate on membrane lipids may be responsible for some, but not all of its bacteriostatic and bactericidal actions.
Chlorhexidine* ; Fluorescence Polarization ; Liposomes ; Membrane Lipids ; Membranes* ; Phospholipids ; Porphyromonas gingivalis* ; Porphyromonas* ; Thiram ; Unilamellar Liposomes

Liposomes with precisely controlled composition are usually used as membrane model systems to investigate the fundamental interactions of membrane components under well-defined conditions. Hydration method is the most common method for liposome formation which is found to be influenced by composition of the medium. In this paper, the effects of small alcohol (ethanol) on the hydration of lipid molecules and the formation of liposomes were investigated, as well as its coexistence with sodium chloride. It was found that ethanol showed the opposite effect to that of sodium chloride on the hydration of lipid molecules and the formation of liposomes. The presence of ethanol promoted the formation of liposomes within a certain range of ethanol content, but that of sodium chloride suppressed the liposome formation. By investigating the fluorescence intensity and continuity of the swelled membranes as a function of contents of ethanol and sodium chloride, it was found that sodium chloride and ethanol showed the additive effect on the hydration of lipid molecules when they coexisted in the medium. The results may provide some reference for the efficient preparation of liposomes.
Ethanol/pharmacology* ; Lipids ; Liposomes

BACKGROUND: Glutathione is a major antioxidant in the body that serves as a substrate for conjugation reactions and regulates cell proliferation. Low levels of glutathione have been linked to cancer, liver problems and other chronic diseases. Studies have shown that oral supplementation is not effective in increasing the glutathione level in the body.

OBJECTIVES: The purpose of the study was to prepare a niosomal formulation of glutathione and to characterize the niosomal formulation. Furthermore, the study compared the effect of the charge inducer in the formulation.

METHODOLOGY: The method was divided to the preparation, characterization and stability study of the niosomal formulation. The niosomal formulation was produced by thin film hydration with varying Span 60 (Sorbitan monostearate) and cholesterol ratios. Niosomal formulation with highest entrapment efficiency was further characterized for mean particle size, surface morphology, and in vitro drug release.

RESULTS AND DISCUSSION: Formulation A entrapped 98.21% of the glutathione. Addition of charge inducer increased its entrapment efficiency to 98.91%. Furthermore, both niosomal formulations released glutathione at pH 7.4 in 1.0M phosphate buffer saline (PBS). The mean vesicular size obtained was 1,242.97 + 40.52nm. Differential Scanning Calorimetry revealed compatibility between glutathione and its excipients. Both formulations do not cause cytotoxicity in human dermal fibroblast. The stability study also revealed that it was stable at 5°C and 40°C for 3 months.

CONCLUSION: Results of this study suggested the potential use of niosomes in the targeted delivery of glutathione. This is the first report on the use of niosomal preparations through thin film hydration technique in the delivery of reduced L-glutathione.

Introduction: Doxorubicin (DOX) and paclitaxel (PTX) are both widely used anticancer drugs with a broad spectrum of antitumor activity, commonly against breast, ovarian, and lung cancers. Currently, these drugs are commercially available in liposomal formulations for their use in chemotherapy. This study generally proposed coconut oil bodies (COB) obtained from Cocos nucifera L. as an alternative carrier for DOX and PTX rather than the currently used liposome. Objectives: This study aimed to compare standard liposome and coconut oil bodies as drug carriers in terms of their microencapsulation efficiencies, lipid profiles, in vitro drug release and stability, as well as their cholesterol levels. Methods: Coconut oil bodies (COB) were isolated and purified from Cocos nucifera L. by modified sucrose gradient method followed by microencapsulation of standard drugs (doxorubicin and paclitaxel) through selfassembly and freeze-thaw method. The two standard drugs were encapsulated using COB and standard liposome. Encapsulation efficiency of both materials were determined. Lipid profiles of both encapsulating materials were analyzed by Fourier-transform infrared spectroscopy, gas chromatography-flame ionization detector, and cholesterol level determination. In vitro drug release and pH stability of both encapsulated drugs were analyzed. Results: Doxorubicin (DOX) and paclitaxel (PTX) were successfully incorporated in COB. Lauric acid was mainly abundant in COB and was able to lower cholesterol levels (5 mg/dL). COB incorporated with DOX and PTX showed stability at acidic and neutral pH. Drug release profile showed a rapid outburst within 3 hours compared to liposome encapsulated DOX and PTX. Conclusion Our study showed the encouraging potentials of using COB as wall materials that will make them attractive candidates for the formulation of pharmaceuticals for optimized drug delivery of cancer chemotherapeutics DOX and PTX
Liposomes ; Doxorubicin ; Paclitaxel

Asiaticoside is a compound extracted from traditional Chinese medicine Centella asiatica, and mainly used in wound healing and scar repair in clinical, with notable efficacy. However, its poor transdermal absorption and short action time restrict its wide application. In this experiment, the reserve-phase-extrusion-lyophilization method was conducted to prepare the lyophilized asiaticoside-loaded flexible nanoliposomes (LAFL). Its characteristics including electron microscope structure, particle size, Zeta potential, entrapment rate, drug-loading rate, stability and drug release were determined with the intelligent transdermal absorption instrument. LAFL were white spheroids, with pH, particle size and zeta potential of 7. 03, 70. 14 nm and - 36. 5 mV, respectively. The average entrapment rate of the 3 batch samples were 31. 43% , and the average asiaticoside content in 1 mg lyophilized simple was 0. 134 mg. The results indicated that LAFL have good physicochemical properties and pharmaceutical characteristics, with an improved transdermal performance.
Animals ; Liposomes ; chemistry ; Nanoparticles ; chemistry ; Triterpenes ; chemistry

AIMTo establish a spectrophotometric method for measurement of the sizes of liposomes for evaluating physical stability of liposomes.

METHODSThe sterically stabilized liposomes (SLs) were prepared by ethanol injection method and extrusion method. The mean cumulant diameters (D) of the vesicles were determined by electron microscopy and dynamic light scattering. On the basis of Rayleigh-Gans-Debye theory, the absorbance at 436 nm per unit lipid concentration (A436 nm/Cp) was measured as a function of vesicle diameter.

RESULTSlog(A436 nm/Cp) was closely related to logD (r2 > or = 0.93, n = 5).

CONCLUSIONThe absorbance of liposomes reflect their relative sizes and can be used to evaluate physical stability of liposomes.

To know the effect of subconjunctival injection of liposome encapsulated cytarabine on proliferation of conjunctival fibroblasts, the conjunctiva was isolated at 180 degrees from the injection site 3 days after subconjunctival injection of the normal saline (control), cytarabine, liposome encapsulated cytarabine, and 1 day after injection of cytarabine, and then those were inoculated in the culture media of fibroblasts. In the case of 3 days after injection of cytarabine, there was 49% and 42% inhibition of proliferation of conjunctival fibroblasts compared with the control respectively. Therefore, the authors concluded that the liposome encapsulated cytarabine is effective on inhibition of proliferation of conjunctival fibroblasts and reduces the frequencies of subconjunctival injection compared with the cytarabine itself.
Conjunctiva ; Culture Media ; Cytarabine* ; Fibroblasts* ; Liposomes*

PURPOSE: The goal of this study is to understand the activation processes that take place within the liposomal formulation of lipophilic diaminocyclohexane platinum (DACH-Pt) complexes, to identify the activated species of this class of compounds, and to use that information to develop a reproducible liposomal formulation of DACH-Pt complexes. MATERIALS AND METHODS: Liposomal DACH-Pt complexes were prepared by lyophilization-rehydration method using PC, PG and PA. Their intraliposomal stability and biological activity were determined by HPLC and in vitro/in vivo experiments. RESULTS: DACH-Pt complexes in a liposomal formulation have shown significant promise in preclinical studies and clinical phase I, II trials. Interestingly, they are prodrugs which converts into one or more undetennined activated platinum species within the liposomes ex vivo. Our studies have shown that the stability of liposomal DACH-Pt complexes is inversely related with the antitumor activity of those complexes. The configuratian of leaving group in the complexes and pH of the liposome suspension affect significantly the degradation/activation process that takes place within the liposomes. DACH-Pt complexes with linear (L10) leaving groups are more stable than complexes with branched ones (B10 and NDDP), but also significantly less potent. The presence of PG and PA in the liposome is a prerequisite for the degradation/activation process of DACH-Pt complexes. As PG and PA formulation gave more dramatic changes of the original complexes than PC alone due to lower pH, the cytotoxicity and antitumor activity at those fonnulations increased against PC alone. DACH-Pt complexes are very stable in liposomes containing PC alone but inactive in vitro/in vivo experiments. CONCLUSION: These results also support that the active species produced within the liposomal DACH-Pt complexes is DACH-Pt-Cl2.
Chromatography, High Pressure Liquid ; Hydrogen-Ion Concentration ; Liposomes* ; Platinum* ; Prodrugs

The coeneal endothelium is essential for the maintenance of normal corneal hydration, thickness, and transparency. However, corneal endothelial cells are incapable of significant proliferation in vivo. As we age, the density of corneal endothelial (CEN) cells gradually decreases. The goal of our study is to explore the possibility of enhancing the proliferation of corneal endothelial cells by introduction of SV 40 large T antigen, a transforming protein. To this end, introduction of protein into CEN cells was assessed by liposome assisted beta-galactosidase transfection in vivo, ex vivo, and in vivo. In all cases, cells treated with liposome-protein complex have shown dramatic blue stain in beta-galactosidase activity staining. This result convinced us that we could artificially introduce a foreign protein into a cell. To ascertain where SV 40 large T antigen is localized in the cell, purified SV 40 large T antigen was transfected into the cells using liposome and its presence was determined immunohistochemically. We show that the liposome delivered SV 40 large is localized in the nucleus and mitotic figures which may suggest its functional activity.
Antigens, Viral, Tumor* ; beta-Galactosidase ; Endothelial Cells* ; Endothelium ; Liposomes ; Transfection*

BACKGROUND: Photodynamic therapy with topical delta-5-aminolevulinic acid (ALA) has been introduced for effective treatment of facial acne. Topical routes for ALA have been explored via a photosensitizer delivery system. OBJECTIVE: We performed this study to evaluate absorption of liposome ALA (Lipo-ALA) into the sebocytes of cultured sebaceous glands and hair organs. METHODS: We cultured KGM sebocytes that were derived from human sebaceous glands. In addition, we cultured William E media pilosebaceous hair units that were isolated from the occipital scalp. Lipo-ALA (10 microgram/ml) and ALA (10 microgram/ml) were added to the 1 ml KGM containing sebocytes for 24 hours and the 1 ml William E media containing pilosebaceous hair units for 6, 24, 48 and 72 hours, respectively. RESULTS: Absorption of Lipo-ALA into the sebocytes of cultured sebaceous gland and hair organs was higher than that of ALA. CONCLUSION: Lipo-ALA may be considered as an effective photosensitizer in photodynamic therapy for facial acne.
Absorption ; Acne Vulgaris ; Hair* ; Humans ; Liposomes* ; Photochemotherapy ; Scalp ; Sebaceous Glands