Receptor-attached amphiphilic terpolymer for selective drug recognition in aqueous solutions

In the present work, a combination of binding studies and molecular docking were employed to demonstrate drug encapsulation and host-guest chemistry in self-assembled micelles consisting of amphiphilic terpolymers. The terpolymer is composed of poly(3-sulfopropyl methacrylate), as the hydrophilic component, poly(n-dodecyl acrylate), as the hydrophobic component and poly(barbiturate receptor), as the component for drug recognition. The combined approach was tested on four model compounds from the family of barbiturates, phenobarbital, mephobarbital, secobarbital, and thiopental, chosen based on their differential hydrogen bonding capabilities. Drug encapsulation and hydrogen-bonding based recognition within the micellar core of the receptor-terpolymer was demonstrated by micellar electrokinetic chromatography. The resulting trends in the binding affinity of the barbiturates to the receptor-terpolymer, were correlated to the trends obtained from computational docking simulations. This receptor-modified polymeric micelle is intended to serve as a model for the design of novel, versatile, and highly selective molecular scaffolds that will provide suitable environment for host-guest chemistry and act as simplified mimics to more complex biological systems.     

Phenobarbital induces cytochrome P-450- and cytochrome P-448-dependent monooxygenases in rat hepatoma cells

The induction by phenobarbital (PB) of aldrin epoxidase (AE) and aryl hydrocarbon hydroxylase (AHH), markers of cytochrome P-450- and cytochrome P-448-dependent monooxygenases, was studied in cell lines derived from Reuber H35 rat hepatoma which differ widely in their degree of differentiation. The following results were obtained: (1) PB induced AE 2-6-fold and AHH 2-4-fold in the differentiated clones, Fao, 2sFou, and C2Rev7 during an exposure period of 72 h. The barbiturate increased AHH but not AE in the dedifferentiated clone H5, the poorly differentiated line H4IIEC3/T, and in the well differentiated line H4IIEC3/G-. (2) Continuous presence of the barbiturate was required for maintaining the induction of the two monooxygenase activities in C2Rev7 cells. (3) Maximum induction of AE was observed at a PB concentration of 1.5-3.0 mM. (4) The effects of 7,8-benzoflavone on AHH-activities induced by phenobarbital in C2Rev7 and H5 cells suggested that they are mediated by cytochrome P-450- and cytochrome P-448-dependent monooxygenase forms, respectively. Thus, the flavonoid had only a slight inhibitory effect on PB-induced AHH in C2Rev7 cells, but strongly inhibited PB-induced AHH in H5 cells. The induction of AE and of 7,8-benzoflavone-inhibitable AHH in 2sFou cells indicated that PB is capable of inducing cytochromes P-450 and cytochrome P-448 in the same cell.     

Nonsubstrate induction of a soluble bacterial cytochrome P-450 monooxygenase by phenobarbital and its analogs

A soluble, cytochrome P-450-dependent fatty acid hydroxylase--epoxidase complex from Bacillus megaterium ATCC 14581 can be induced more than 100-fold by the addition of phenobarbital or one of its analogs (hexobarbital) to the growth medium. These barbiturate inducers are apparently not substrates for the enzyme nor do they activate the monooxygenase in the cell-free system. The induction efficiency of both phenobarbital and hexobarbital can be significantly increased with respect to monooxygenase activity by autoclaving the inducer in the growth medium rather than by adding it to the medium after autoclaving. Turnover numbers of about 3 000 nmoles of substrate oxygenated per min per nmole of P-450 were obtained in crude cell-free preparations obtained from maximally induced cultures. Our data indicate that products formed by heating phenobarbital or hexobarbital in the growth medium are significantly better inducers of monooxygenase activity than are the unaltered drugs.     

Effect of alcohol feeding mode on the biosynthesis of poly (3-hydroxybutyrate-co-3-hyroxyvalerate)

An alcohol utilizing Alcaligenes eutrophus produced poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) copolymer under phosphate limitation. Fermentation was performed for 42-46 h in a computer-controlled 5-L working volume fed-batch fermentor using ethanol and propanol as carbon sources. The culture experienced phosphate limitation in approximately 19 h. When propanol was used as a sole carbon source, 24 g/L of copolymer with 36.5 mol % of hydroxyvalerate (HV) was produced at a polymer yield of 0.41 g polymer/g alcohol (g/g) and an average polymer production rate of 0.08 g polymer/g residual biomass-h (g/g-h). Two experiments switching alcohol after phosphate exhaustion resulted in better polymer production (g/L), polymer yield (g/g) on alcohol, HV yield (g/g) on propanol, and average polymer production rate (g/g-h) as compared to propanol run without alcohol switching. One switching experiment was from a mixture of 50% ethanol and 50% propanol to 100% propanol and the other experiment was from 100% ethanol to a mixture of 65% ethanol and 35% propanol. Polymer yield for these two experiments was 0.51 g/g and 0.46 g/g, respectively. However, HV mol % in the copolymer for these two runs (30.8 mol % 12.6 mol % respectively) was lower compared to propanol run without alcohol switching (3605 mol %). Direct switch from ethanol to propanol did not support cell growth and polymer production. Polymer production rate and polymer yield changed with time, and the pattern was dependent upon the alcohol feeding mode. (c) 1994 John Wiley & Sons, Inc.     

Retinitis Pigmentosa Reduces the Risk of Proliferative Diabetic Retinopathy: A Nationwide Population-Based Cohort Study

Purpose

To study the association between retinitis pigmentosa (RP) and the progression of diabetic retinopathy (DR).

Methods

Using the Longitudinal Health Insurance Database 2000 of Taiwan, we identified individuals with an initial diagnosis for RP during the period of 1997–2008. A non-RP comparison group, 10-fold frequency matched by sex, age, index year and the year of diabetes diagnosed, were randomly selected from the same database. The occurrence of DR was observed for all subjects until the end of 2009. The Kaplan-Meier curves were used to illustrate the cumulative probability of developing DR for the RP group and comparison groups. The hazard ratio (HR) of DR for the RP group relative to the comparison group was estimated using Cox proportional hazards model after adjusting for potential confounders.

Results

The Kaplan-Meier curves were not statistically significant different between the RP group and the comparison group. However, the RP group had a higher cumulative probability of developing DR during the first six to seven years. The cumulative probability kept increasing and became higher in the comparison group but remained unchanged in the RP group. The HR for the RP patients comparing with the comparison group was 0.96 (95% confidence interval (CI) = 0.43–2.14). Stratified by severity, RP was associated with a non-statistically significant reduced risk of proliferative DR (PDR) (HR = 0.70, 95% CI = 0.16–3.14). The HR for non-proliferative DR (NPDR) was 1.08 (95% CI = 0.40–2.86).

Conclusion

In this study, RP was not statistically significant associated with the incidence of DR.     

Effects of Low Dissolved-Oxygen Concentrations on Poly-(3-Hydroxybutyrate-co-3-Hydroxyvalerate) Production by Alcaligenes eutrophus

The bacterial copolyester poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) was produced with Alcaligenes eutrophus DSM 545 from glucose and sodium propionate in a fed-batch fermentation with both nitrogen limitation and low dissolved-oxygen concentrations. When the dissolved-oxygen content was kept between 1 and 4% of air saturation during the polymer accumulation phase, the yield of 3-hydroxybutyrate (3HB) monomer from glucose was not affected, but the propionate-to-3-hydroxyvalerate (3HV) monomer yield was two to three times (0.48 to 0.73 mol of 3HV mol of propionate consumed(sup-1)) that observed in a control experiment (0.25 mol mol(sup-1)), where the accumulation-phase dissolved-oxygen concentration was 50 to 70% of air saturation. The overall polymer productivity of the fermentation was somewhat decreased by low dissolved-oxygen contents, owing to a slower 3HB production rate. The effect of a low dissolved-oxygen concentration is probably attributable to a reduction of the oxygen-requiring decarbonylation of propionyl-coenzyme A (CoA) to acetyl-CoA.     

硫辛酸抗再灌期心律失常与外源性自由基所致动作电...

By means of Langendorff method the isolated rat heart was perfused with Krebs Henseleit solution. Following ligation of the left descending coronary artery for 10 min the heart was reperfused for 3 min. The incidence of ventricular fibrillation in the reperfusion period was 100%, and the normal sinus rhythm time was shortened to 29 s within 3 min of reperfusion. Administration of lipoic acid (6.8 X 10(-6)-1.7 X 10(-4) mol/L) to the perfusate significantly reduced the incidence of ventricular fibrillation to 33-50% and prolonged the normal sinus rhythm time to 97-107 s. APA, RP, and Vmax recorded from the guinea pig papillary muscle were depressed due to the deleterious effect of xanthine oxidase and hypoxanthine free radical generating system. Under the treatment of lipoic acid (3.5 X 10(-5) mol/L), the depression of APA, RP, and Vmax were significantly relieved. This confirms that lipoic acid treatment, owing to its free radical scavenger effect, is able to protect myocardium from free radical induced electrophysiological abnormalities, and consequently decrease the incidence of malignant arrhythmias.     

Additional comments on migraine therapy

The symptoms and clinical management of alcohol, barbiturate and benzodiazepine withdrawal syndromes are discussed in this article. People who suffer alcohol withdrawal should be admitted to hospital if they have medical or surgical complications or severe symptoms; supportive care and pharmacotherapy, especially diazepam loading, are the essential components of treatment. Barbiturate withdrawal requires pharmacotherapy and admission to hospital for patients who have taken more than 0.4 g/d of secobarbital or an equivalent amount of another barbiturate for 90 days or longer, or 0.6 g/d or an equivalent dose for 30 days or longer, or who have had withdrawal seizures or delirium; phenobarbital loading is recommended. Regular benzodiazepine therapy that has lasted at least 3 months should be gradually stopped. Short-acting agents should be replaced with long-acting ones, such as diazepam, to avoid withdrawal symptoms. Most of these patients can be managed on an outpatient basis.     

Effect of Carbon Substrates on Rock Phosphate Solubilization by Bacteria from Composts and Macrofauna

Five of the 207 isolates from different composts, farm waste compost (FWC), rice straw compost (RSC), Gliricidia vermicompost (GVC), and macrofauna, showed rock phosphate (RP) solubilization in buffered medium in plate culture. When tested in RP broth medium, all five strains, Enterobacter cloacae EB 27, Serratia marcescens EB 67, Serratia sp. EB 75, Pseudomonas sp. CDB 35, and Pseudomonas sp. BWB 21, showed gluconic acid production and solubilized RP. Based on cellulose-degrading and P-solubilizing ability, two strains were selected for further studies. In the presence of different carbon sources, both strains showed a drop in pH and solubilized RP. P released was maximum with glucose (1212 and 522 μmol) and minimum with cellobiose (455 and 306 μmol) by S. marcescens EB 67 and Pseudomonas sp. CDB 35, respectively. Glucose dehydrogenase (GDH) activity was 63 and 77% with galactose and 35 and 46% with cellobiose when compared to glucose (100%) by EB 67 and CDB 35, respectively. Both strains solubilized RP in the presence of different crop residues. EB 67 and CDB 35 showed maximum cellulase activity (0.027 units) in the presence of rice straw and a mixture of rice straw and root. P solubilized from RP in the presence of pigeonpea root was 134 and 140 μmol with EB 67 and CDB 35. Significantly, these bacteria isolated from composts and macrofauna solubilized rock phosphate in the presence of various pure carbon substrates and crop residues and their importance in soil/rhizosphere conditions is discussed.     

Increased Risk of Acute Angle Closure in Retinitis Pigmentosa: A Population-Based Case-Control Study

Purpose

To investigate the association between retinitis pigmentosa (RP) and acute angle closure during a 15-year follow-up period.

Methods

Using the Taiwan Longitudinal Health Insurance Database 2000, we identified 382 RP patients based on the diagnostic code of RP (International Classification of Diseases, 9^th Revision, Clinical Modification (ICD-9-CM) 362.74) made during 1996–2010, excluding subjects under age of 20 years at diagnosis or subjects undergoing lens extraction before the index date. The control group included 3820 randomly selected non-RP subjects matched with the RP patients in age, gender and the index date of diagnosis. The incidence of acute angle closure during the study period was observed based on an ICD-9-CM code of 365.22. Cochran-Mantel-Haenszel test was used to determine the odds ratio (OR) of having acute angle closure in RP patients.

Results

The mean age at the diagnosis of RP was 51.1years (standard deviation [SD] 16.7). Acute angle closure occurred in 5 RP patients (1.3%) and in 15 controls (0.4%). The mean age with the acute angle closure was 53.3 years (SD 8.0) in RP patients and 64.6 years (SD 8.4) in controls (P = 0.015). After adjusting for age, gender and comorbid disorders, RP patients had 3.64-fold (95% confidence interval [CI], 1.29–10.25, P<0.001) greater odds of having acute angle closure. After stratification for gender and age, the risk of acute angle closure in RP was higher in patients under age of 60 years (adjusted OR 11.84; 95% CI, 2.84–49.48) and male patients (adjusted OR 19.36; 95% CI, 3.43–109.40)(both P = 0.001).

Conclusions

RP patients had increased risk of acute angle closure than controls. Contrary to the fact that angle closure disease is more prevalent in elderly females in general population, acute angle closure attack occurred earlier in life and the risk was higher in males among RP patients.     

Synthesis and self-assembly of well-defined poly(amino acid) end-capped poly(ethylene glycol) and poly(2-methyl-2-oxazoline)

Poly(ethylene glycol) (PEG) and poly(2-methyl-2-oxazoline) (PMOx) are water-soluble, biocompatible polymers with stealth hemolytic activities. Poly(amino acid) (PAA) end-capped PEG and PMOx were prepared using amino-terminated derivatives of PEG and PMOx as macroinitiators for the ring-opening polymerization of γ-benzyl protected l-glutamate N-carboxyanhydride and S-benzyloxycarbonyl protected l-cysteine N-carboxyanhydride, respectively, in the presence of urea, at room temperature. The molecular weight of the PAA moiety was kept between M(n) = 2200 and 3000 g mol(-1). PMOx was polymerized by cationic ring-opening polymerization resulting in molecular weights of M(n) = 5000 and 10,000 g mol(-1), and PEG was a commercial product with M(n) = 5000 g mol(-1). Here, we investigate the self-assembly of the resulting amphiphilic block copolymers in water and the effect of the chemical structure of the block copolymers on the solution properties of self-assembled nanostructures. The PEG-block-poly(amino acid), PEG-b-PAA, and PMOx-block-poly(amino acid), PMOx-b-PAA, block copolymers have a narrow and monomodal molecular weight distribution (PDI < 1.3). Their self-assembly in water was studied by dynamic light scattering and fluorescence spectroscopy. In aqueous solution, the block copolymers associate into particles with hydrodynamic radii (R(H)) ranging in size from R(H) 70 to 130 nm, depending on the block copolymer architecture and the polymer molecular weight. Larger R(H) and critical association concentration values were obtained for copolymers containing poly(S-benzyloxycarbonyl-l-cysteine) compared to their poly(γ-benzyl-L-glutamate) analogue. FTIR investigations revealed that the poly(γ-benzyl-L-glutamate) block adopts a helical conformation, while the poly(S-benzyloxycarbonyl-L-cysteine) block exists as β-sheet.     

From defined reactive diblock copolymers to functional HPMA-based self-assembled nanoaggregates

This paper describes the synthesis of functional amphiphilic poly( N-(2-hydroxypropyl) methacrylamide)-block-poly(lauryl methacrylate) copolymers by RAFT polymerization via the intermediate step of activated ester block copolymers (pentafluoro-phenyl methacrylate). Block copolymers with molecular weights from 12000-28000 g/mol and PDIs of about 1.2 have been obtained. The amphiphilic diblock copolymers form stable super structures (nanoaggregates) by self-organization in aqueous solution. The diameters of these particles are between 100 and 200 nm and depend directly on the molecular weight of the block copolymer. Furthermore, we investigated the impact of these nanoaggregates on cell viability and on the motility of adherent cells. Cytotoxicity was investigated by the MTS test and the fluctuation in cell shape was monitored employing ECIS (electrical cell-substrate impedance sensing). In these investigations, the formed particles are not cell toxic up to a concentration of 2 mg/mL. Thus, our polymeric particles offer potential as polymer therapeutics.     

Investigation of the role of hydrophilic chain length in amphiphilic perfluoropolyether/poly(ethylene glycol) networks: towards high-performance antifouling coatings

The facile preparation of amphiphilic network coatings having a hydrophobic dimethacryloxy-functionalized perfluoropolyether (PFPE-DMA; M(w) = 1500 g mol(-1)) crosslinked with hydrophilic monomethacryloxy functionalized poly(ethylene glycol) macromonomers (PEG-MA; M(w) = 300, 475, 1100 g mol(-1)), intended as non-toxic high-performance marine coatings exhibiting antifouling characteristics is demonstrated. The PFPE-DMA was found to be miscible with the PEG-MA. Photo-cured blends of these materials containing 10 wt% of PEG-MA oligomers did not swell significantly in water. PFPE-DMA crosslinked with the highest molecular weight PEG oligomer (ie PEG1100) deterred settlement (attachment) of algal cells and cypris larvae of barnacles compared to a PFPE control coating. Dynamic mechanical analysis of these networks revealed a flexible material. Preferential segregation of the PEG segments at the polymer/air interface resulted in enhanced antifouling performance. The cured amphiphilic PFPE/PEG films showed decreased advancing and receding contact angles with increasing PEG chain length. In particular, the PFPE/PEG1100 network had a much lower advancing contact angle than static contact angle, suggesting that the PEG1100 segments diffuse to the polymer/water interface quickly. The preferential interfacial aggregation of the larger PEG segments enables the coating surface to have a substantially enhanced resistance to settlement of spores of the green seaweed Ulva, cells of the diatom Navicula and cypris larvae of the barnacle Balanus amphitrite as well as low adhesion of sporelings (young plants) of Ulva, adhesion being lower than to a polydimethyl elastomer, Silastic T2.     

3-Penten-2-one,a novel aldehyde adduct,is a biomarker for increased acetaldehyde in urine

Diagnostic profiling of urine for volatile compounds of around 400 patients using headspace solid-phase microextraction (HS-SPME) in alkaline conditions identified 3-penten-2-one (approximately 1 to >6.3 μmol/L) in 26 patients. Five were in barbiturate coma. 3-Penten-2-one, previously of unknown origin, was shown to be formed by aldol condensation of acetaldehyde with acetone or acetoacetate during analysis. Semi-quantification of acetaldehyde using in-fibre derivatisation HS-SPME, showed high concentrations in five urine (33–348 μmol/L) and two plasma (17 and 43 μmol/L) samples. Hence, urinary 3-penten-2-one is a useful biomarker for increased accumulation of acetaldehyde during abnormal metabolic stress.     

Synthesis and characterization of amphiphilic polyphosphates with hydrophilic graft chains and cholesteryl groups as nanocarriers

Amphiphilic polyphosphate graft copolymers with varied densities of cholesteryl esters and hydrophilic graft chains were prepared, and the solution properties of the graft copolymers were evaluated. Polyphosphates were synthesized as backbones by ring-opening polymerization of 2-isopropyl-2-oxo-1,3,2-dioxaphospholane (IPP), 2-(2-oxo-1,3,2-dioxaphosphoroyloxyethyl-2-bromoisobutyrate) (OPBB), and 2-choresteryl-2-oxo-1,3,2-dioxaphospholane (ChOP) using triisobutylaluminum as an initiator. Three types of polyphosphates (PIBr(x)Ch(y), x = number of OPBB units in a polymer; y = number of ChOP units in a polymer) such as PIBr4, PIBr6Ch1, and PIBr3Ch2 were obtained. The molecular weights of these polymers were 2.4 x 10(4), 2.4 x 10(4), and 2.6 x 10(4) g/mol, respectively. 2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted from the OPBB sites in PIBr(x)Ch(y) via atom transfer radical polymerization (ATRP) in EtOH. In each polymer system, the molecular weight of the graft polymer was linear with conversion. Furthermore, the polymer radical concentration remained constant during polymerization; that is, the molecular weights of the graft chains were easily controllable with polymerization time. The solution properties of amphiphilic PIBr(x)Ch(y)-g-PMPCs were investigated by the methods of surface tension measurement, light scattering, and fluorescence probe. The transition point (cmc) of the surface tension of the PIBr(x)Ch(y)-g-PMPCs aqueous solution decreased with an increase in the number of ChOP units in a graft polymer. Particularly, PIBr3Ch2-g-PMPC14.9K formed nanosized associates (R(h) = 7.5 nm) with 2.2 molecules above 0.1 wt %. v79 cells were used to evaluate the cytotoxicity of the graft polymers, but no cytotoxicity was observed. The graft polymers containing cholesteryl groups effectively enhanced the solubility of paclitaxel in an aqueous solution.     

Newborn response to cationic amphiphilic drugs

Administration of various cationic amphiphilic drugs in utero results in induction of a phospholipid storage disorder in many tissues, particularly in lungs. In addition to the phospholipidosis in utero, drug exposure results in toxicity to the offspring; newborn rats die within 48 h of birth. Although drug-induced pulmonary pathological changes appear to be involved in the observed mortality, this relationship remains unclear. In contrast to mammals, administration of cationic amphiphilic drugs to the chick embryo seems not to induce phospholipid storage in the tissues examined. Treatment of newborn rats directly with these drugs also induces phospholipidosis in several tissues including lung and kidney; however, mortality does not occur. Concurrent administration of phenobarbital and chlorphentermine reduces or prevents amphiphilic drug-induced phospholipid storage in newborn rat lung and kidney. Modification of chlorphentermine actions by phenobarbital may be caused by alterations in amphiphilic drug excretion, metabolism, and catabolic phospholipase activity. Evidence thus indicates that regardless of age, animals appear susceptible to the effects of cationic amphiphilic drugs; however, species and tissues examined, as well as specific drug administration, play an important role in the observed qualitative and quantitative responses.     

TGF‐β1 rs1982073 polymorphism contributes to radiation pneumonitis in lung cancer patients: a meta‐analysis

Transforming growth factor beta 1(TGF‐β1) polymorphism was associated with radiation pneumonitis (RP) susceptibility, but their results have been inconsistent. The PubMed and CNKI were searched for case‐control studies published up to Januray 01, 2016 was Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta‐analysis, we assessed eight publications involving 368 radiation pneumonitis cases and 855 controls of the association between TGF‐β1 T869C (rs1982073) and G915C (rs1800471) polymorphism and RP susceptibility. Our analysis suggested that TGF‐β1 T869C rs1982073 polymorphism was associated with lower RP risk for CT combined CC versus TT model (OR = 0.58, 95% CI = 0.43–0.77). However, for the G915C rs1800471 polymorphism, no association was found between the polymorphism and the susceptibility to RP in GC combined CC versus GG model (OR = 0.82, 95% CI = 0.50–1.35). These results from the meta‐analysis suggest that T869C rs1982073 polymorphism of TGF‐β1 may be associated with RP risk, and there may be no association between G915C polymorphism and RP risk.     

Synthesis and hydration properties of pH-sensitive p(HEMA)-based hydrogels containing 3-(trimethoxysilyl)propyl methacrylate

An amphiphilic hydrogel network was synthesized from a cross-linked poly(2-hydroxyethyl methacrylate) backbone copolymerized with the monomers 3-(trimethoxysilyl)propyl methacrylate (PMA) and dimethylaminoethyl methacrylate (DMAEMA) using tetraethylene glycol diacrylate (TEGDA) as cross-linker and using the radical initiator system comprising N,N,N',N'-tetramethylethylenediamine and ammonium peroxydisulfate. The degree of hydration of hydrogel slabs was investigated as functions of varying monomer compositions and cross-link density and as a function of pH and ionic strength of the bathing medium. As much as a 45% increase in hydration was observed for hydrogels containing 15 mol % DMAEMA upon reducing the pH of the bathing medium from 8.0 to 2.0. This confirms the pH-modulated swelling of amine-containing hydrogels. Increasing the concentration of TEGDA cross-linker from 3 to 12 mol % in a 10 mol % DMAEMA-containing hydrogel resulted in only a 10% reduction in the degree of hydration of the gel. There was, however, a 40-50% reduction in the degree of hydration of a 15 mol % DMAEMA hydrogel upon increasing the molar composition of PMA from 0 up to 20 mol %. The presence of PMA confers hydrophobic character that reduces hydration and introduces additional cross-links that reduce network mesh size. The water content of the hydrogel was consistently higher in buffers of lower ionic strength. The reversible pH-dependent swelling observed in these studies, along with the control of cross-link density afforded by the PMA component, endows these biocompatible materials with potential for use in pH-controlled drug delivery of more hydrophobic drugs and present new compositions for in vitro and in vivo biocompatibility studies.     

Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer by <Emphasis Type="Italic">Azotobacter chroococcum</Emphasis> strain 7B

The ability of Azotobacter chroococcum strain 7B, producer of poly(3-hydroxybutyrate) (PHB), to synthesize its copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV)) was studied. It was demonstrated, for the first time, that A. chroococcum strain 7B was able to synthesize P(3HB-co-3HV) with various molar rates of HV in the polymer chain when cultivated on medium with sucrose and carboxylic acids as precursors of HV elements in the PHB chain, namely, valeric (13.1–21.6 mol %), propanoic (3.1 mol %), and hexanoic (2.1 mol %) acids. Qualitative and functional differences between PHB and P(3HB-co-3HV) were demonstrated by example of the release kinetic of methyl red from films made of synthesized polymers. Maximal HV incorporation into the polymer chain (28.8mol %) was recorded when the nutrient medium was supplemented with 0.1% peptone on the background of 20 mM valerate. These results suggest that that the studied strain can be regarded as a potential producer of not only PHB but also P(3HB-co-3HV).