Liposome-Encapsulated Hemoglobin Processing Methods

Zheng, S.; Zheng, Yaoming; Beissinger, Richard L.; Fresco, Raoul

doi:10.3109/10731199209119655

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…Regardless, we have been able to prepare liposome/DNA complexes using cationic lipid/EPC mixtures that exhibit the same size distribution as cationic lipid/DOPE mixtures through the use of ultrasonic cavitation. We suggest that other methods of size reduction, which employ mechanical force based on cavitation, such as homogenization, 53 high-pressure extrusion, 54 or microfluidization, [55][56][57] may also be able to produce particles of small, uniform diameter from these complexes.…”

Section: Discussionmentioning

confidence: 98%

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

Wasan¹,

Reimer²,

Bally³

1996

Journal of Pharmaceutical Sciences

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Cationic liposomes bound to plasmid DNA are currently used for in vitro and in vivo gene therapy applications, but such complexes readily form large, heterogeneous aggregates that are not appropriate for pharmaceutical development. More importantly, size heterogeneity makes studies focused on optimizing gene transfer to cells difficult to conduct or understand. For this reason we have evaluated the effect of microprobe sonication on these complexes in an effort to achieve process-controlled size homogeneity. Complexes were prepared using a 7.2 kb reporter plasmid and the following liposomal lipid combinations: DDAB/DOPE (50:50 mol %), DDAB/DOPE/PEG-PE (50:45:5 mol %), DDAB/EPC (50:50 mol %), DDAB/EPC/PEG-PE (50:45:5, 50:40:10, 50:35:15 mol %), DODAC/DOPE (50:50 mol %), and DODAC/EPC (50:50 mol %) (DDAB, dimethyldioctadecylammonium bromide; DOPE, dioleoylphosphatidylethanolamine; PEG-PE, monomethoxypolyethylene glycol2000 succinate- distearoylphosphatidylethanolamine; EPC, egg phosphatidylcholine; DODAC, dioleoyldimethylammonium chloride). The influence of complex composition and lipid:DNA ratio was evaluated. Particle size was determined before and after complexation and again after sonication using the quasi-elastic light scattering technique. DNA integrity was assessed via agarose gel electrophoresis. Finally, gene transfection was evaluated using CHO cells that were transfected in vitro with sonicated and unsonicated complexes. It is established in this study that size reduction can occur, but this is dependent on cationic and neutral lipid composition and, in some cases, lipid:DNA ratio. Surprisingly, the process of sonication leaves a significant percentage of the plasmid DNA intact and capable of in vitro transfection. This study shows that plasmid DNA can be protected from damage due to sonication by liposome complex formation. This may indicate that more common pharmaceutical methods for size reduction which subject particles to mechanical stress may be applicable in preparation of liposome/DNA formulations for in vivo application.

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Section: Discussionmentioning

confidence: 98%

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

Wasan¹,

Reimer²,

Bally³

1996

Journal of Pharmaceutical Sciences

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“…Multiple emulsion droplet sizes were examined by dispersion of the multiple emulsion into a gelatin solution (0.1 g per 100 ml of aqueous outer phase); a homogeneous dispersion was obtained [12]. The diluted sample was placed in a Howard Cell (Rascher and Betzold, Inc., Chicago, IL) and was examined under a microscope at 100X magnification.…”

Section: Drop Size Analysismentioning

confidence: 99%

Ketamine-in Oil-in-Water Multiple Emulsion for Prolonged Drug Release

Zheng

Beissinger

Sehgal

et al. 1999

Journal of Dispersion Science and Technology

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A preparation of Ketamine [2-(Chlorophenyl)-2-(methylamino) cyclohexanone, C IlH 16CINO, anesthetic agent] in oil in water multiple emulsion for prolonged drug release was formulated and evaluated. Ketamine, the cyclohexylamine, is used as a shortacting anaesthetic in humans and in some animal species [I]. Ketamine is poorly bound to plasma proteins and has a half-life of approximately 4 hours following intravenous injection [2]. Ketamine leaves the blood very rapidly to be distributed into the tissues with a high lipid solubility [2]. The recommended dosage of intravenous Ketamine is 2.5-20mglkg [3]. The LD50 injected intraperitoneally in mice and rats is 100 times the intravenous and 30 times the intramuscular dose used in humans.The objective of this study was to test the concept that a multiple emulsion could be formulated which has high porosity and lower viscosity at 3rC consistent with its intended use for sustained drug release and to prolong the half-life of the anesthesia. The results showed that the Ketamine (100mg/ml in inner phase) released 8.2% at 10 minutes, 67.0% at 30 minutes, and 95.5% at 60 minutes from the Ketamine/OIW multiple emulsion in a well-controlled manner. 235

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“…solution concentration, other methods developed recently involved modified reverse phase evaporation method, double emulsion method and modified film hydration method [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Liposome Microencapsulations Without Using Any Organic Solvent

Zheng

Alkan-Önyüksel

Beissinger

et al. 1999

Journal of Dispersion Science and Technology

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Liposomes are microscopic vesicles composed of phospholipid bilayers surrounding discrete aqueous compartment Eventhough phospholipid bilayers are formed spontaneously in water, their conventional preparation methods involve either organic solvents or detergent molecules, Organic solvents may create a serious safety problem during liposome manufacturing especially on a large scale and can cause denaturation of proteins and affect the membrane properties. Liposomes are very promising carriers for protein drugs which have aroused great interests in the field of pharmaceutics in these recent years,The objective of this study was to develop a new dispersion process to prepare Iiposomes without the usage of organic solvents and detergents, The approach involved the usage of a microfludizer for the extrusion and homogenization of aqueous dispersion of phospholipids, and a modified evaporator in order to increase lipid thin film surface area, The properties of the liposomes prepared by the novel method were superior to the liposomes prepared by conventional methods,

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Liposome-Encapsulated Hemoglobin Processing Methods

Cited by 5 publications

References 39 publications

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

Plasmid DNA is Protected against Ultrasonic Cavitation-Induced Damage when Complexed to Cationic Liposomes

Ketamine-in Oil-in-Water Multiple Emulsion for Prolonged Drug Release

Liposome Microencapsulations Without Using Any Organic Solvent

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