The technology of synthesis, extraction and modification of biodegradable polyhydroxybutyrate (PHB) is introduced briefly in this article. It is also summarized that the research progress in application of PHB in drug delivery and tissue engineering.
Biocompatible Materials ; chemistry ; Drug Delivery Systems ; Hydroxybutyrates ; chemistry ; Tissue Engineering

In this review, we presented the industrial status of biomanufactured polyhydroxyalkanoates (PHA), including poly (3-hydroxybutyrate) (PHB), poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly (3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB)), and poly (3-hydroxybutyrate-3-hydroxycaproate) (PHBH). A lot of modification studies, aimed at solving problems of poor thermal stability, narrow processing window and other drawbacks of PHA, are discussed. The properties of PHA can be optimized by using proper modification method, in order to expand its applications.
3-Hydroxybutyric Acid ; Biotechnology ; Hydroxybutyrates ; Polyesters ; Polyhydroxyalkanoates ; chemistry

Besides medical application, 4-hydroxybutyrate (4-HB) is a precursor of P3HB4HB, a bioplastic showing excellent physical properties and degradability. Escherichia coli S17-1 (pZL-dhaT-aldD) can transform 1, 4-butanediol (1,4-BD) into 4HB with participation of cofactor NAD. To enhance productivity, nicotinic acid phosphoribosyltransferase (PncB) and nicotinamide adenine dinucleotide synthetase (NadE) were overexpressed to increase intracellular nicotinamide adenine dinucleotide concentration and promote reaction process. The shake flask fermentation result showed that the conversion rate increased by 13.03% with help of PncB-NadE, leading to 4.87 g/L 4HB from 10 g/L 1,4-BD, and productivity was increased by 40.91% to 1.86 g/g. These results demonstrated that expression of PncB and NadE is beneficial for conversion of 1,4-BD to 4HB.
Amide Synthases ; metabolism ; Butylene Glycols ; chemistry ; metabolism ; Escherichia coli ; metabolism ; Fermentation ; Hydroxybutyrates ; chemistry ; metabolism ; Pentosyltransferases ; metabolism

Ultra-fine Poly(3-hydroxybutyrate)/soya protein isolates fibers were prepared via electrospinning technique. The structure and morphology of the electrospun fibers were determined by scanning electron microscope (SEM), thermal analysis (DSC-TGA) and optical micrographs. The effects of melt stability, concentration,electrical potential and the distance between the spinning tip and the collector upon the morphology of electrospun fibers were also discussed. The results showed that glycerin was surface active agent in the melt PHB/soya protein blends. It was also found that electrospinning process promotes the crystallation ,which may be caused by the orientation of molecule chains due to electrical force stretching.
Biocompatible Materials ; chemistry ; Biodegradation, Environmental ; Electrochemistry ; Glycerol ; chemistry ; Hydroxybutyrates ; chemistry ; Microscopy, Electron, Scanning ; Nanostructures ; Polyesters ; chemistry ; Polymers ; chemistry ; Soybean Proteins ; chemistry

AIMTo optimize the preparation of sustained release prednisolone-poly (hydroxybutyrate-cohydroxyvalerate) (PNS-PHBV) nanospheres (NP) using the novel biodegradable materials PHBV as the carriers and PNS as a model drug.

METHODSPNS-PHBV nanospheres were prepared by ultrasonic-emulsion technique. The diameter, its distribution and Zeta potential on the surface of particles were measured by means of Zetasizer.

RESULTSThe diameter of NP is in the range of 50-250 nm. The drug loading of NP increases but incorporation efficiency and Zeta potential dramatically decrease with increasing ratio of the feeding quantities of drug to those of carriers. The drug release behavior in vitro appeared to have biphasic characteristics with initial burst effect. The more burst effect, the less the diameters of nanoparticles. The longest release time was up to 32 h.

CONCLUSIONThe technology of preparation is reasonable and PNS-PHBV nanoparticle showed significant sustained release.

Anti-Inflammatory Agents ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Hydroxybutyrates ; chemistry ; Nanotechnology ; Polyesters ; chemistry ; Polymers ; chemistry ; Prednisolone ; administration & dosage ; chemistry ; Technology, Pharmaceutical

OBJECTIVES: To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood. METHODS: Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected. RESULTS: The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively. CONCLUSIONS GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.
4-Butyrolactone/chemistry* ; Animals ; Chromatography, Liquid ; Exosomes/chemistry* ; Hydroxybutyrates/chemistry* ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium Oxybate/analysis* ; Tandem Mass Spectrometry/methods*

Halohydrin dehalogenase is of great significance for biodegradation of the chlorinated pollutants, and also serves as an important biocatalyst in the synthesis of chiral pharmaceutical intermediates. A putative halohydrin dehalogenase (HheTM) gene from Tistrella mobilis KA081020-065 was cloned and over-expressed in Escherichia coli BL21 (DE3). The recombinant enzyme was purified by Ni-NTA column and characterized. Gel filtration and SDS-PAGE analysis showed that the native form of HheTM was a tetramer. It exhibited the highest activity at 50 degrees C. The nature and pH of the buffer had a great effect on its activity. The enzyme maintained high stability under the alkaline conditions and below 30 degrees C. HheTM catalyzed the transformation of ethyl(S)-4-chloro-3-hydroxybutyrate in the presence of cyanide, to give ethyl (R)-4-cyano-3-hydroxybutyrate, a key intermediate for the synthesis of atorvastatin.
3-Hydroxybutyric Acid ; chemistry ; Bacterial Proteins ; genetics ; metabolism ; Cloning, Molecular ; Escherichia coli ; Hydrolases ; genetics ; metabolism ; Hydroxybutyrates ; chemistry ; Recombinant Proteins ; genetics ; metabolism ; Rhodospirillaceae ; enzymology ; genetics

OBJECTIVE: A rapid color test for screening gamma-hydroxybutyric acid (GHB) and its precursor gamma-butyrolactone(GBL) was investigated in drink and urine samples. METHODS: In an acidic solution, GHB was converted to GBL, which reacted with hydroxylamine hydrochloride in presence of sodium hydroxide, forming hydroxamate. A purple complex was formed when hydroxamate reacted with ferric chloride in acidic condition. RESULTS: Detection limit concentrations of GHB in drinks were between 0.5-2 mg/mL, less than the popular abuse concentrations of GHB. This method was usable for urine, with detection limit concentration 0.5 mg/mL. Interferences of common organic solvents and narcotics and depressants were surveyed. CONCLUSION This method is simple, safe, and rapid; it facilitates rapid screening of GHB and GBL in clinic and forensic laboratories.
4-Butyrolactone/urine* ; Alcoholic Beverages/analysis* ; Anesthetics/urine* ; Beverages/analysis* ; Forensic Medicine/methods* ; Humans ; Hydrogen-Ion Concentration ; Hydroxybutyrates/urine* ; Solvents/chemistry* ; Sulfuric Acids/chemistry*

This experiment was designed to investigate the feasibility of transplanatation of using porous PHB as cell carrier for the transplanatation of adrenocortical cells. Adrenocortical cells from rat adrenal gland were separated and cultured in vitro. The effect of PHB on the proliferation and secretory function of adrenocortical cells were evaluated by MTT and RIA methods. Then adrenocortical cells were seeded into porous PHB. After the cells were cultured in vitro for about seven days, they were implanted into the rats having undergone bilateral adrenalectomy. The changes of blood corticosterone and aldosterone and the local histological changes in these rats were observed. Adrenocortical cells were able to grow and survive on PHB. No effect on the proliferation and secretory function of adrenocortical cells were observed. Most bilateral adrenalectomized rats bearing the transplanted adrenocortical cells within PHB (study group) survived longer than did the adrenalectomized rats in control group. The blood corticosterone level and aldosterone level of study group were higher than those of control group. It was found that PHB has no effects on the survival, proliferation and secretory function of adrenocortical cells. Adrenocortical cells within PHB can survive a period of time and can secrete corticosterone and aldosterone which can meet the needs of the adrenalectomized rats. PHB can degrade slowly in vivo. It is feasible to perform transplantation of adrenocortical cells using porous PHB as cell carrier.
Adrenal Cortex ; cytology ; Aldosterone ; blood ; urine ; Animals ; Biodegradation, Environmental ; Cell Proliferation ; Cell Transplantation ; Cells, Cultured ; Coculture Techniques ; Corticosterone ; blood ; urine ; Hydroxybutyrates ; chemistry ; pharmacology ; Male ; Polyesters ; chemistry ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVE: The possibility for the identification of GHB administration through hair analysis was investigated to provide method and information for toxicology examination of GHB. METHODS A GC/MS assay for GHB in hair was developed. Endogenous levels of GHB in hair, time course of GHB in hair, relationship between GHB levels in hair and hair color or administration dose were also established by guinea pig model. RESULTS: Endogenous levels of GHB in guinea pig black hair and human black hair were (3.01 +/- 1.41) ng/mg (n=28) and (1.02 +/- 0.27) ng/mg (n=20), respectively. GHB levels in black hair were increased by GHB administration and related with drug dosage, and also much higher than in brown and white hair. CONCLUSION Analysis of GHB in hair is suitable for investigation of GHB abuse in forensic toxicology and GHB level in segmental analysis compared with endogenous level of GHB may provide useful information about GHB administration.
Animals ; Dose-Response Relationship, Drug ; Forensic Toxicology/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Guinea Pigs ; Hair/chemistry* ; Hair Color ; Humans ; Hydroxybutyrates/analysis* ; Male ; Substance Abuse Detection/methods* ; Time Factors