1.Preparation of polyelectrolyte microcapsules containing ferrosoferric oxide nanoparticles.
Xiao-Qing LIU ; Chun-Li ZHENG ; Jia-Bi ZHU
Acta Pharmaceutica Sinica 2011;46(1):115-120
In this study, polyelectrolyte microcapsules have been fabricated by biocompatible ferrosoferric oxide nanoparticles (Fe3O4 NPs) and poly allyamine hydrochloride (PAH) using layer by layer assembly technique. The Fe3O4 NPs were prepared by chemical co-precipitation, and characterized by transmission electron microscopy (TEM) and infrared spectrum (IR). Quartz cell also was used as a substrate for building multilayer films to evaluate the capability of forming planar film. The result showed that Fe3O4 NPs were selectively deposited on the surface of quartz cell. Microcapsules containing Fe3O4 NPs were fabricated by Fe3O4 NPs and PAH alternately self-assembly on calcium carbonate microparticles firstly, then 0.2 molL(-1) EDTA was used to remove the calcium carbonate. Scanning electron microscopy (SEM), Zetasizer and vibrating sample magnetometer (VSM) were used to characterize the microcapsule's morphology, size and magnetic properties. The result revealed that Fe3O4 NPs and PAH were successfully deposited on the surface of CaCO3 microparticles, the microcapsule manifested superparamagnetism, size and saturation magnetization were 4.9 +/- 1.2 microm and 8.94 emu x g(-1), respectively. As a model drug, Rhodamin B isothiocyanate labeled bovine serum albumin (RBITC-BSA) was encapsulated in microcapsule depended on pH sensitive of the microcapsule film. When pH 5.0, drug add in was 2 mg, the encapsulation efficiency was (86.08 +/- 3.36) % and the drug loading was 8.01 +/- 0.30 mg x m(L-1).
Calcium Carbonate
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chemistry
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Capsules
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Chemical Precipitation
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Drug Carriers
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Drug Compounding
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methods
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Drug Delivery Systems
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Electrolytes
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chemistry
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Ferrosoferric Oxide
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chemistry
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Magnetite Nanoparticles
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Microscopy, Electron, Scanning
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Microscopy, Fluorescence
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Particle Size
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Rhodamines
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administration & dosage
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chemistry
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Serum Albumin, Bovine
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administration & dosage
;
chemistry
2.Effect of NaCl in outer water phase on the characteristics of BSA-loaded PLGA sustained-release microspheres fabricated by a solid-in-oil-in-water emulsion technique.
Xiang-lian ZHOU ; Jin-tian HE ; Zhi-tao ZHOU ; Shu-fen MA ; Yang JIANG ; Ying WANG
Acta Pharmaceutica Sinica 2010;45(8):1057-1063
The aim of this study is to investigate the critical factor affecting the properties of PLGA microspheres fabricated by a solid-in-oil-in-water (S/O/W) emulsion technique with BSA as a model protein. Prior to encapsulation, the BSA microparticles were fabricated by a modified freezing-induced phase separation method. The microparticles were subsequently encapsulated into PLGA microspheres by S/O/W emulsion method, then Motic BA200 biological microscope, confocal laser scanning microscope, scanning electron microscope were used to observe the structure of S/O/W emulsion and PLGA microspheres. The protein content extracted or released from BSA microspheres was measured by Bradford protein assay method. It was found that NaCl added in the outer aqueous phase effectively suppressed material exchange between the inner and outer phase of S/O/W emulsion. Then, the structure and permeability of obtained microspheres were influenced. As a result, with the increase of NaCl concentration in the outer aqueous phase, the encapsulation efficiency of microspheres significantly increased from 60% to more than 85%, the burst release of microspheres reduced from 70% to 20%, and the particle size decreased from 103 microm to 62 microm. Furthermore, the rehydration of encapsulated protein was also retarded and then integrity of BSA was successfully protected during encapsulation process. In vitro release test showed that BSA released from PLGA microspheres in a sustained manner for more than 30 days.
Delayed-Action Preparations
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Drug Compounding
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Emulsions
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chemistry
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Lactic Acid
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administration & dosage
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chemistry
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Microscopy, Confocal
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Microscopy, Electron, Scanning
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Microspheres
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Oils
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Particle Size
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Polyglycolic Acid
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administration & dosage
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chemistry
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Serum Albumin, Bovine
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administration & dosage
;
chemistry
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Sodium Chloride
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chemistry
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Water
3.Preparation of cationic dextran microspheres loaded with tetanus toxoid and study on the mechanism of protein loading.
Chun-li ZHENG ; Xiao-qing LIU ; Jia-bi ZHU ; Yu-na ZHAO
Acta Pharmaceutica Sinica 2010;45(9):1183-1187
The aim of this study is to prepare cationic biodegradable dextran microspheres loaded with tetanus toxoid (TT) and to investigate the mechanism of protein loading. Positively charged microspheres were prepared by polymerization of hydroxylethyl methacrylate derivatized dextran (dex-HEMA) and dimethyl aminoethyl methacrylate (DMAEMA) in an aqueous two-phase system. The loading of the microspheres with TT was based on electrostatic attraction. The net positive surface charge increased with increasing amounts of DMAEMA. Confocal images showed fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) could penetrate into cationic dextran microspheres but not natural dextran microspheres. TT loading efficiency by post-loading was higher compared with by pre-loading. Even though TT is incorporated in the hydrogel network based on electrostatic interaction, still a controlled release can be achieved by varying the initial network density of the microspheres.
Delayed-Action Preparations
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Dextrans
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chemistry
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Drug Carriers
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chemistry
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Hydrogels
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chemistry
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Methacrylates
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chemistry
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Microscopy, Confocal
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Microspheres
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Particle Size
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Polymerization
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Serum Albumin, Bovine
;
chemistry
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Tetanus Toxoid
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administration & dosage
;
chemistry
4.Recent advances in the study of accelerated blood clearance phenomenon of PEGylated liposomes.
Huan XU ; Kai-Qian WANG ; Wei-Wei HUANG ; Yi-Hui DENG ; Da-Wei CHEN
Acta Pharmaceutica Sinica 2010;45(6):677-683
It is generally believed that liposomes modified with polyethylene glycol (PEG) have no or lower immunogenicity. However, based on many recent literatures, when the PEGylated liposomes were repeatedly applied to the same animal, the immune responses occurred. The first injection of PEGylated liposomes resulted in a reduction in the circulation time and an increase in hepatic and splenic accumulation of the second dose of PEGylated liposomes in a time-interval, which was called "accelerated blood clearance (ABC)" phenomenon. Such immunogenicity of PEGylated liposomes presents a barrier in the research of liposomal formulations and their use in the clinics. This review focused on the definition, the method of verification, the development of the reason for ABC phenomenon, influencing factors of ABC phenomenon, and discussed if other PEGylated nanocarriers also induce ABC phenomenon.
Animals
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Antibiotics, Antineoplastic
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administration & dosage
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pharmacokinetics
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Doxorubicin
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administration & dosage
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pharmacokinetics
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Drug Carriers
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Immunoglobulin M
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biosynthesis
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blood
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Liposomes
;
administration & dosage
;
blood
;
pharmacokinetics
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Liver
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metabolism
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Metabolic Clearance Rate
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Particle Size
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Polyethylene Glycols
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administration & dosage
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metabolism
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pharmacokinetics
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Serum Albumin, Bovine
;
pharmacokinetics
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Spleen
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immunology
;
metabolism
5.Preparation, activity and targeting ability evaluation in vitro on folate mediated epigallocatechin-3-gallate albumin nanoparticles.
Yuan-gang ZU ; Shuai YUAN ; Xiu-hua ZHAO ; Yu ZHANG ; Xiao-nan ZHANG ; Ru JIANG
Acta Pharmaceutica Sinica 2009;44(5):525-531
To study the preparation, activity and targeting ability evaluation in vitro on epigallocatechin-3-gallate (EGCG) bovine serum albumin nanoparticles targeting to PC-3 cells, the folate mediated EGCG bovine serum albumin nanoparticles (FA-EGCG-BSANP) were prepared by desolvation process. The morphology and particle size of the nanoparticles were determined by atomic force microscope (AFM). HPLC was used to analyse the entrapment efficiency and drug loading rate of EGCG The amount of folate conjugation on the BSANP was determined by quantitative ultraviolet (UV) spectrophotometer analysis. The targeting ability to PC-3 was observed using laser scanning confocal microscope (LSCM) and fluorophotometer microscope. And the activity of FA-EGCG-BSANP was mensurated by MTT method. The morphology and particle size distribution of FA-EGCG-BSANP were uniform and even with the mean particle size of 200 nm. The entrapment efficiency and loading rate of EGCG were (81.5 +/- 1.8) % and (29.3 +/- 0.6) %, respectively, and the amount of folate conjugation was 18.363 microg x mg(-1) BSA. The FA-EGCG-BSANP uptakes by cultured PC-3 cells were 23.65 times the amount of EGCG-BSANP in a concentration dependant manner. The lethality of PC-3 cells treated with FA-EGCG-BSA was 82.8%, while those treated with EGCG and EGCG-BSANP were 58.6% and 55.1%, respectively. And lethality of PC-3 cells was positively correlated with the nanoparticles uptake amount. FA-EGCG-BSANP can significantly promote EGCG to PC-3 cells sites and improve their efficacy, which is considered to an experimental foundation for further research on its activity, targeting ability and metabolism in vivo.
Antineoplastic Agents, Phytogenic
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administration & dosage
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pharmacokinetics
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pharmacology
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Catechin
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administration & dosage
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analogs & derivatives
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pharmacokinetics
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pharmacology
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Cell Death
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drug effects
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Cell Line, Tumor
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Drug Carriers
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Drug Compounding
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Drug Delivery Systems
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methods
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Folic Acid
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administration & dosage
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chemistry
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pharmacokinetics
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Humans
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Male
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Nanoparticles
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Particle Size
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Prostatic Neoplasms
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metabolism
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pathology
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Serum Albumin, Bovine
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chemistry
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pharmacokinetics
;
pharmacology
6.Effect of ciprofloxacin and chloramphenicol on humoral immune response elicited by bovine albumin encapsulated in niosomes.
Jitender MADAN ; Dinesh KAUSHIK ; Satish SARDANA ; Dn MISHRA
Acta Pharmaceutica Sinica 2007;42(8):905-910
The aim is to evaluate the effect of ciprofloxacin and chloramphenicol on anti-BSA antibody production triggered by bovine albumin encapsulated in non-ionic surfactant vesicle, niosomes. Reverse phase evaporation method was adopted to entrap the antigen in colloidal carrier composed of Span 80 and Span 85 followed by simultaneous characterization for particle size, entrapment efficiency and in vitro release. The protein content was determined by Bradford method using UV Visible Spectrophotometer at 595 nm. Humoral immune response was measured in terms of systemic IgG antibody titre by ELISA method. Experimental data indicated that 7 : 3 molar ratio of Span 80 and cholesterol based niosomal formulation possessed maximum (39.8 +/- 2.9)% of soluble protein. Ciprofloxacin markedly (P < 0.05) decreased the antibody titre. In contrast, chloramphenicol did not reduce the antibody titre significantly in comparison to control group (P > 0.05). It is necessary to explore the effect of a vaccine antigen when a candidate is medicated with a therapeutic agent, which might help in programming a new drug management and vaccination programme.
Animals
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Antibody Formation
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drug effects
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Chloramphenicol
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administration & dosage
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pharmacology
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Ciprofloxacin
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administration & dosage
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pharmacology
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Drug Carriers
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Hexoses
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Immunoglobulin G
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blood
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Liposomes
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Male
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Particle Size
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Rats
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Rats, Wistar
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Serum Albumin, Bovine
7.The entrapped efficiency of BSA liposome.
Dong-Zhi HOU ; Chang-Ke LIU ; Qi-Neng PING ; Xiao-Hui LIANG
Acta Pharmaceutica Sinica 2007;42(5):545-549
BSA liposomes were prepared with approximately 100 nm mean particle size under rather gentle experiment conditions, and two-colorimetric coomassie brilliant blue protein was employed to measure the free drug in the entrapped efficiency (EE%) determination of BSA liposomes. Gel filtration was used to measure the EE%, and several Sephadex gels were examined by the separation of liposomes and free drug. To determine the free drug, three methods were compared on two-colorimetric UV spectrophotography, Bradford and two-colorimetric coomassie brilliant blue, separately. Two-colorimetric coomassie brilliant blue process increased the accuracy and improved the sensitivity of the assay about 20-fold comparing with the Bradford method. Two-colorimetric coomassie brilliant blue assay appeared to be more sensitive and showed broader dynamic range to measure the free BSA in the EE% determination of BSA liposome.
Colorimetry
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Drug Carriers
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Drug Compounding
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Electrophoresis, Gel, Two-Dimensional
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Liposomes
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Particle Size
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Rosaniline Dyes
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Serum Albumin, Bovine
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administration & dosage
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analysis
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Spectrophotometry, Ultraviolet
8.Fabrication of alginate microsphere for controlled release and investigation of its release characteristics in vitro.
Qingyi HE ; Lisheng WEN ; Qiang LI ; Jianzhong XU ; Fei LUO
Journal of Biomedical Engineering 2007;24(6):1301-1304
This study sought to producte alginate sodium microsphere for controlled release bovine serum albumin(BSA) and to investigate the protein release profile of the BSA-alginate sodium microsphere in vitro, which threw some light on the angiogenesis of tissue engineering bone with vascular endothelial growth factor (VEGF) controlled release under stress. The BSA-alginate sodium microsphere was fabricated with W/O emulsification and ion cross-linking method using alginate sodium. The appearance, microsphere diameter and envelopment rate were detected, and the release characteristics of the BSA-alginate sodium microsphere in vitro was investigated. The alginate microsphere was found to be spherical in shape and evenly distributed. Its mean grain diameter was determined to be 230 +/- 60 microm, carrying capacity 80.3 microg/mg and envelopment rate 61%. Smooth controlled release in BSA-alginate sodium microsphere was shown to last more than 2 weeks. Alginate sodium proved an excellent biodegradable material for protein or polypeptide controlled release. The emulsification and ion cross-linking method was noted to be simple; it was propitious to the structural and functional stablility of protein or polypeptide, thus leading to the prolonged efficacious time of the microsphere.
Alginates
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administration & dosage
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chemistry
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Animals
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Cattle
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Delayed-Action Preparations
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chemical synthesis
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Drug Carriers
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Glucuronic Acid
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administration & dosage
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chemistry
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Hexuronic Acids
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administration & dosage
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chemistry
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Microspheres
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Serum Albumin, Bovine
;
administration & dosage
9.Preparation and release behavior of chitosan scaffolds encapsulating proteins loaded in PLGA microspheres.
Gang HAN ; Hai-Liang CHEN ; Xiao-Yi SUN ; Jian-Qing GAO ; Wen-Quan LIANG
Acta Pharmaceutica Sinica 2006;41(6):493-497
AIMTo prepare cells scaffolds with the characteristics of sustained release of proteins.
METHODSChitosan scaffolds was prepared by freeze-drying. Porosity and water content of scaffolds were determined. Bovine serum album (BSA) was selected as a model protein. Poly (lactic-co-glycolic acid) (PLGA) microspheres were prepared by double emulsion solvent evaporation and encapsulated into chitosan scaffolds. The morphology of PLGA microspheres and various scaffolds were observed using scanning electron microscope. Release behavior of BSA from various chitosan scaffolds was investigated.
RESULTSThe chitosan scaffold represents porous. At the -70 degrees C of quenching temperature, the porosity and water content of chitosan scaffolds were 78.6% +/- 1.5% and 85.1% +/- 6.2%, respectively. PLGA microspheres can be uniformly encapsulated into scaffolds without any morphology change. Significant sustained release of BSA from PLGA microspheres encapsulated into scaffolds was obtained. The cumulative release at 168 h was only 33.5%, while that of BSA from chitosan scaffolds at 24 h was above 90%. The release behavior can be controlled by adjusting the amount of chitosan in scaffolds and the type of PLGA.
CONCLUSIONThe novel chitosan scaffolds encapsulating PLGA microspheres proved to be a promising cells scaffolds with controlling the release of growth factors in tissue engineering.
Chitosan ; administration & dosage ; chemistry ; Drug Carriers ; Freeze Drying ; methods ; Lactic Acid ; chemistry ; Microspheres ; Polyglycolic Acid ; chemistry ; Polymers ; chemistry ; Serum Albumin, Bovine ; metabolism ; Tissue Engineering ; methods
10.Study on modified guar gum microsphere as a protein drug carrier.
Fuchu OU ; Liming ZHANG ; Rufu CHEN
Journal of Biomedical Engineering 2006;23(6):1267-1270
A biodegradable modified guar gum microsphere was prepared for the first time by ionic gelation of the guar gum derivative containing quarternary ammonium group with tripolyphosphate at room temperature in the absence of emulsifying agent or organic solvent. Its average particle diameter was about 140 microm and the particle size had a narrow and normal gauss distribution. From the loading experiment of bovine serum album (BSA) with various concentrations, it was found that the encapsulation efficiency is more than 80%. By the investigation of in vitro release from the BSA-loaded microsphere, it was found that the BSA had a continuous release for more than 6 hours and the release percentage was affected by the initial concentration of the BSA and temperature.
Biocompatible Materials
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chemistry
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Drug Carriers
;
chemistry
;
Drug Delivery Systems
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Galactans
;
chemistry
;
Mannans
;
chemistry
;
Microspheres
;
Plant Gums
;
chemistry
;
Proteins
;
administration & dosage
;
Serum Albumin, Bovine
;
administration & dosage
Result Analysis
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