In situ forming PLGA implant for 90 days controlled release of leuprolide acetate for treatment of prostate cancer

In prostate cancer, hormone therapy via leuprolide acetate drug (LUP) is used to lower the level of testosterone down to castration level to effectively control the development of prostate cancer. The objective of this study was to evaluate the effective parameters in degradation and controlled release of an injectable in situ formed polymeric implant, loaded with leuprolide acetate, in order to achieve an optimum formulation for sustained drug release for 90 days with minimum burst release. The main problem associating with such implants is their high burst release. Designing an injectable implant with sustained and minimum burst release has thus become an attractive challenge in drug delivery field. Effects of type of poly(lactic‐co‐glycolic acid) 75:25 copolymers (RG752, RG756) and addition of nano‐hydroxyapatite (HA) particles on degradation rates of the implants and release profiles were examined in vitro and in vivo in a rabbit animal model. Results showed that implants containing polymers with higher molecular weights had significantly lower weight loss and molecular weight reduction. Adding nanoparticles of hydroxyapatite into poly(lactic‐co‐glycolic acid) implants caused further reduction in degradation rates, leading to a more sustained drug release in vivo, with reduced burst release. Different conventional kinetic models were applied to drug release and degradation data. The degradation data fit well to the first‐order degradation model. Higuchi model was the best kinetic release model fitted to the experimental in vitro release data. This study led to an optimum formulation (RG756:RG752 3:1 + 5% HA) with sustained leuprolide release and testosterone suppression over a 90‐day period with significant decrease of burst release phase (50%, p < 0.001) compared with the conventional Eligard formulation. The histopathology test showed that the formulated implant had no effects of toxicity or tissue necrosis in organs of the animal model. Copyright © 2017 John Wiley & Sons, Ltd.     

Sodium chloride nanorods from nanorods of one-dimensional pencil-shaped sodium coordination polymer

By considering the structure of one-dimensional pencil-shaped organometallic coordination polymer that was previously reported, we designed and synthesized [Na(μ₂-Hdcpa)(μ₃-dcpa)] _n (1), [Hdcpa = 2,4-dichlorophenoxyacetic acid], which has one-dimensional pencil-shaped structure too. The Na atoms are surrounded with the aromatic phenyl rings of Hdcpa similar to graphite of a pencil. Metalophilic interactions also exists in 1 between Na(I) ions similar to argentophilic interaction in our previous compound which results in formation of chain structure similar to graphite structure of a pencil. Compound 1 nanorods were formed under ultrasonic irradiation and applied as template to fabricate sodium chloride nanorods. The interesting feature of our work is the formation of sodium chloride nanorods from compound 1 nanorods which have one-dimensional structure in the solid state.     

Synthesis of new dyes containing double tetrazole groups for sensitization of TiO<Subscript>2</Subscript> nanoparticles in dye-sensitized solar cells

Di(1H-tetrazol-5-yl)methane is employed as a new electron acceptor group in the synthesis of two metal-free organic dyes containing triphenylamine donor group. Dye-sensitized nanocrystalline TiO₂ solar cell (DSSC) applying these novel dyes is constructed for consideration of their photovoltaic properties. The electronic properties of the dyes are also considered with the aid of theoretical calculations. The DSSC constructed from 4-(2,2-di(1H-tetrazol-5-yl)vinyl)-N,N-diphenylaniline (T1) shows a short-circuit photocurrent density of 13.38 mA cm^?2, an open circuit voltage of 578 mV, and a fill factor of 0.54, with a resulted solar energy-to-electricity conversion efficiency of 4.18% under simulated 1 sun irradiation (100 mW cm^?2). This result reveals that the dye with the di(1H-tetrazol-5-yl)methane anchoring group injects more electrons to the conduction band of TiO₂ in comparison with its analogs with single tetrazole ring in their anchoring group. It is found that in spite of a red-shift of the absorption spectrum resulted from the lengthening of the molecule, the dye with two di(1H-tetrazol-5-yl)methane groups gives lower performance than the dye with a single electron acceptor.     

A new scheme for solving nonlinear Stratonovich Volterra integral equations via Bernoulli’s approximation

In this paper, an efficient method for solving nonlinear Stratonovich Volterra integral equations is proposed. By using Bernoulli polynomials and their stochastic operational matrix of integration, these equations can be reduced to the system of nonlinear algebraic equations with unknown Bernoulli coefficient which can be solved by numerical methods such as Newton’s method. Also, an error analysis is valid under fairly restrictive conditions. Furthermore, in order to show the accuracy and reliability of the proposed method, the new approach is compared with the block pulse functions method by some examples. The obtained results reveal that the proposed method is more accurate and efficient than the block pulse functions method.     

Multiple solutions for non-homogeneous degenerate Schrödinger equations in cone Sobolev spaces

The present paper deals with the study of semilinear and non-homogeneous Schrödinger equations on a manifold with conical singularity. We provide a suitable constant by Sobolev embedding constant and for p ∈ (2, 2?) with respect to non-homogeneous term g(x) ∈ L ₂ ^n/2 (B), which helps to find multiple solutions of our problem. More precisely, we prove the existence of two solutions to the problem 1.1 with negative and positive energy in cone Sobolev space H _2,0 ^1,n/2 (B). Finally, we consider p = 2 and we prove the existence and uniqueness of Fuchsian-Poisson problem.     

A facile synthesis of novel 1,4-benzoxazepin-2-one derivatives

An efficient and simple synthesis of 1,4-benzoxazepin-2-one derivatives has been achieved via the reaction of isoquinoline, activated acetylenes, and 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone in water without using any catalyst. This one-pot reaction occurs in high yields under mild conditions.     

Density functional studies of influences of Ni triad metals and solvents on oxidative addition of MeI to [M(CH3)2(NH3)2] complexes and C-C reductive elimination from [M(CH3)3(NH3)2I] complexes

Three metal square planar complexes of the type [M(CH₃)₂(NH₃)₂] (M = Ni, Pd, Pt), with a systematic variation in the metals, are chosen to investigating their S_N2-type oxidative addition reactions with methyl iodide by using the B3LYP levels of theory. The oxidative addition was found to take place via a transition state with a nearly linear arrangement of the I-CH₃-M moiety. Solvation effects in these oxidative addition reactions were also investigated. Considering the nature of the metal centre and solvation effects, the following conclusions emerge: (i) addition of MeI is exothermic for all three metals, and Pt is predicted to react with a much lower barrier than either Pd or Ni. The results describe that the MeI addition would be expected to be more favourable with the complex bearing the third-row metal (platinum) as compared to the other triad metals, nickel or palladium, in which case a more strongly bound MeI adduct is formed with a lower activation barriers and the reaction being more exothermic; (ii) the reaction is very difficult to occur in low polar solvents, such as benzene, due to the high barrier which is induced by dissociation of iodide anion from methyl group, but the reaction easily occurs in polar solvents, such as acetonitrile; this is attributed to the ability of polar solvents to solvate and therefore stabilize the related polar intermediate ion pair. Ethane reductive elimination from the M(VI) complexes fac-[M(CH₃)₃(NH₃)₂I] were also studied, indicating that the Ni(IV) and Pd(IV) complexes are very prone to undergo the reductive elimination while the Pt(IV) analogous is less reactive towards the reductive elimination. The results indicate that in contrast to the Me-Me reductive elimination, the S_N2 oxidative addition reaction of MeI to M(II) is much less sensitive to the nature of the metal centre, suggesting that the nucleophilicity of M(II) in [M(CH₃)₂(NH₃)₂] does not change significantly as one moves from M = Ni to Pt.     

1,3-Dibromo-5,5-dimethylhydantoin as an efficient homogeneous catalyst for synthesis of benzoxazoles, benzimidazoles, and oxazolo[4,5-b]pyridines

Abstract  

A simple and highly efficient method for synthesis of benzoxazoles, benzimidazoles, and oxazolo[4,5-b]pyridines is described. Condensation of orthoesters with o-substituted anilines or 2-amino-3-hydroxypyridine was performed in the presence of catalytic amounts of commercially available, inexpensive, and moisture-stable 1,3-dibromo-5,5-dimethylhydantoin under solvent-free conditions. The corresponding heterocycles were obtained in good to excellent yields. The main advantages of the present procedure are mild reaction conditions, short reaction times, high yields of products, easy work-up, and absence of solvent.     

Cloning and Expression of Che a 1, the Major Allergen of <Emphasis Type="Italic">Chenopodium album</Emphasis> in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Chenopodium album is a weedy annual plant in the genus Chenopodium. C. album pollen represents a predominant allergen source in Iran. The main C. album pollen allergens have been described as Che a 1, Che a 2, and Che a 3. The aim of this work was to clone the Che a 1 in Escherichia coli to establish a system for overproduction of the recombinant Che a 1 (rChe a 1). In order to clone this allergen, the pollens were subjected to RNA extraction. A full-length fragment encoding Che a 1 was prepared by polymerase chain reaction amplification of the first-strand cDNA synthesized from extracted RNA. Cloning was carried out by inserting the cDNA into the pET21b (+) vector, thereafter the construct was transformed into E. coli Top10 cells and expression of the protein was induced by IPTG. The rChe a 1 was purified using histidine tag in recombinant protein by means of Ni–NTA affinity chromatography. IgE immunoblotting, ELISA, and inhibition ELISA were done to evaluate IgE binding of the purified protein. In conclusion, the cDNA for the major allergen of the C. album pollen, Che a 1, was successfully cloned and rChe a 1 was purified. Inhibition assays demonstrated allergic subjects sera reacted with rChe a 1 similar to natural Che a 1 in crude extract of C. album pollen. This study is the first report of using the E. coli as a prokaryotic system for Che a 1 cloning and production of rChe a 1.     

Competition of methyltrioxorhenium (MTO) with osmium tetroxide (OsO4) for pyridines binding: Ligand binding assay

Competition of methyltrioxorhenium (MTO) with osmium tetroxide (OsO₄) toward L = pyridine and its derivatives, based on the equilibrium constant for the reaction OsO₄·L + MTO = MTO·L + OsO₄, has been measured. A successful correlation of log K_eq with the Hammett σ constants of the substituents on the ligands was realized. A negative reaction constant, obtained for the reactions, shows that a more positive charge expands on the pyridine nitrogen in the complex MTO·L as compared with the complex OsO₄·L. So, the rhenium center acts as a better electron acceptor than osmium center. The thermodynamic parameters have been obtained and an excellent linear relationship was observed between the enthalpy and entropy of the reactions.