Novel pH-Sensitive Lactic Acid Oligomer Grafted Chitosan Hydrogel for Controlled Drug Release

A pH-sensitive hydrogel, using chitosan as hydrophilic segment and lactic acid oligomer (LAO) as hydrophobic segment, was successfully synthesized through a dehydration reaction between amino and carboxyl groups. Scanning electron microscope (SEM) images revealed that the channel-like network structure of the as-prepared hydrogels, which plays an important role in controllable drug release behavior, was gradually collapsed with increasing content of lactic acid. Fourier-transform infrared (FTIR) spectra were obtained to demonstrate the occurrence of the dehydration reaction. Furthermore, the swelling ratio measurement and release study were performed, and the results showed that the chitosan/LAO hydrogel had an outstanding pH-sensitive property, and thus has high potential for usage in controlled-drug release.     

The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers as drug carriers

The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers (HP-g-PEO) as drug carriers were investigated. The HP-g-PEO consisting of hydrophobic HP-g-PEO core and hydrophilic poly(ethylene glycol) arms was prepared by the cation ring-opening polymerization. A series of HP-g-PEO samples with different degree of branching (DB) were synthesized under various reaction temperatures. Nanoparticles (NP) were obtained by self-assembly of HP-g-PEO in aqueous media. The structure of resulting HP-g-PEO was characterized by IR, ¹³CNMR and GPC. Dynamic light scattering and transmission electron microscopy were applied to characterize the sizes and size distributions of NP. The results demonstrated that the mean diameters of NP were less than 100 nm, which exhibited uniform spherical formations and narrow size distributions. Using hydrophobic drug Probucol (PRO) as model drug, the particle sizes of drug loaded NP were larger than relative blank NP. The drug loading efficiency (LE) and incorporation efficiency (IE) of these NP were achieved to 35 and 89%, respectively. The in vitro release of PRO from the NP exhibited a sustained release and the cumulative drugs released for more than 600 h. The most important factor to affect drug release was the value of DB of HP-g-PEO. With the DB of HP-g-PEO increasing, the size and size distribution of NP decreased as well as the release rate. However, the small DB was beneficial to the LE of NP. Nanoparticle size and size distribution, LE, IE, and drug release rate were slightly affected by the initial solution concentration of polyethers. The co-incorporated hydrophilic drug had influence slightly on the release of drug from drug loaded NP. The results of in vitro drug release suggested that the core/shell NP performed good controlled release behaviors with potential practice as novelty drug delivery vehicles.     

A spectrophotometric and thermodynamic study of the charge-transfer complexes of iodine with nortriptyline and imipramine drugs in chloroform and dichloromethane solutions

The interaction of iodine as electron acceptor with nortriptyline and imipramine drugs as electron donors has been investigated spectrophotometrically at various temperatures in chloroform and dichloromethane solutions. The observed time dependence of the charge–transfer band and subsequent formation of in solution were related to the slow transformation of the initially formed iodine: drug outer complex to an inner electron donor–acceptor (EDA) complex, followed by fast reaction of the inner complex with iodine to form a triiodide ion. The pseudo-first-order rate constants and activation parameters for the transformation process were evaluated from the absorbance-time data. Stoichiometrices of the complexes were defined by the Job’s method of the continuos variation and obtaind 2: 1 for iodine: drug complexes. The formation constants and molar absorptivities were evaluated from the absorbance-mole ratio data. Thermodynamic parameters of the complexes have been determined from the temperature dependence of the stability constant by Van’t Hoff equation.     

竹红菌乙素(HB)在C60与三乙胺分子间电子转移反应中的光催化作用

用ESR方法探讨了在C₆₀与三乙胺(Et₃ N)的分子间电子转移反应中竹红菌乙素(HB)的光催化作用.通过对Et₃N/C₆₀/HB电子转移反应体系及其中间体的研究得知:在HB存在的条件下,可通过光催化电子转移反应机理,实现室温下由Et₃N到基态C₆₀的分子间电子转移     

Hidden chemistry of substituted aniline radical cations in water: a mechanistic study

Absolute rate constants for hydroxyl radical, azide radical, and hydrated electron reactions with a sulfa drug 4,4'‐diamino diphenyl sulfone (dapsone) in water have been evaluated using electron pulse radiolysis technique. Absolute rate constants for hydroxyl radical and azide radical were determined as (8.4 ± 0.3) × 10⁹ and (5.6 ± 0.5) × 10⁹ M^?1 s^?1, respectively. The reduction of dapsone with the hydrated electron occurred with rate constant of (9.2 ± 0.1) × 10⁹ M^?1 s^?1. Hydroxyl radical reactions result in the synchronous formation of adduct as well as anilino radical. The interesting observation is that the yield of the anilino radical increases with increase in pH. Contrary to this, the yield of the adduct decreases with pH. We propose that hydroxyl radical adds predominantly to the aniline. In contrast, the reaction of azide radical with the dapsone suggests that the reaction occurs at the –NH₂ moiety of the aniline ring. The free radical electron transfer from dapsone to parent radical cation of non‐polar solvent also results in the formation of anilino radical only suggesting that the radical cation of dapsone has a short lifetime. The reaction of hydrated electrons with the dapsone suggests that the reaction occurs at different reaction site. The experimental results supported by theoretical calculations of this study provide fundamental mechanistic parameters that probably decide the fate of the radical cation of aniline derivatives. Copyright © 2014 John Wiley & Sons, Ltd.     

Template-directed hydrothermal synthesis of hydroxyapatite as a drug delivery system for the poorly water-soluble drug carvedilol

In order to improve the dissolution rate and increase the bioavailability of a poorly water-soluble drug, intended to be administered orally, the biocompatible and bioactive mesoporous hydroxyapatite (HA) was successfully synthesized. In the present study, mesoporous HA nanoparticles were produced using Pluronic block co-polymer F127 and cetyltrimethylammonium bromide (CTAB) as templates by the hydrothermal method. The obtained mesoporous HA was employed as a drug delivery carrier to investigate the drug storage/release properties using carvedilol (CAR) as a model drug. Characterizations of the raw CAR powder, mesoporous HA and CAR-loaded HA were carried out by the scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, N₂ adsorption/desorption, thermogravimetric analysis (TGA), and UV-VIS spectrophotometry. The results demonstrated that CAR was successfully incorporated into the mesoporous HA host. In vitro drug release studies showed that mesoporous HA had a high drug load efficiency and provided immediate release of CAR compared with micronized raw drug in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.8). Consequently, mesoporous HA is a good candidate as a drug carrier for the oral delivery of poorly water-soluble drugs.     

PHOTOCATALYSIS OF HYPOCRELLIN (HB) IN THE ELECTRON TRANSFER REACTION OF C60 AND TRIETHYLAMINE

用ESR方法探讨了在C     

Influence of the electric field on the electron transport in photosynthetic reaction centers

The effect of an electric field on the electron transfer in the bacterial reaction centers is investigated. The rate constants and quantum yields affected by the electric field for wild type (WT) and reaction center (RC) mutant of Rhodobacter capsulatus were computed. The dependence of the asymmetry of electron transfer in electric field on the temperature was evaluated. We found stable electron transfer for WT of the reaction center towards an electric field in comparison with the F(L121)D mutant of RC. We found quantum yields sensitive to the variation of the medium reorganization energy at low temperatures and strong electric fields. The quantum yields for unoriented RC samples were also calculated.     

Evaluation of an oral carrier system in rats: bioavailability and gastrointestinal absorption properties of curcumin encapsulated PBCA nanoparticles

A new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of curcumin (CUR), a poorly soluble drug. The formulation was optimized by orthogonal design and the optimal PBCNs loading CUR exhibited a spherical shape under transmission electron microscopy with a range of 40?C400?nm. Physicochemical state of CUR in PBCN was investigated by X-ray diffraction and the possible structure changes occurring in CUR after conjugating with polybutylcyanoacrylate were studied with FTIR. The results indicated that CUR in PBCN was in a non-crystalline state and CUR was encapsulated in PBCN without chemical reaction. The oral pharmacokinetic study was conducted in rats and the relative bioavailability of CUR encapsulated PBCNs to the crude CUR was more than 800%. The in situ absorption experiment in rat intestine indicated the absorption was first order with passive diffusion mechanism. The absorption results in various segments of intestine showed that the main absorption sites were ileum and colon. It can be concluded that PBCNs as an oral carrier can significantly improve the oral absorption of a poorly soluble drug.     

Coaxial Electrospun Poly(L‐Lactic Acid) Ultrafine Fibers for Sustained Drug Delivery

A coaxial electrospinning technique to fabricate core‐shell ultrafine fiber mats for drug delivery application is described in this paper. Poly (L‐lactic acid) (PLLA) and tetracycline hydrochloride (TCH) were employed as the shell and core materials, respectively. To investigate the feasibility of the resulting fiber mats for use as drug release carriers, these electrospun fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and tensile testing. In vitro drug release behavior was also examined by ultraviolet‐visible (UV‐VIS) spectroscopy. Results indicated that a reservoir‐type drug release device can be conveniently obtained through encapsulating TCH in the PLLA ultrafine fiber. The size of the ultrafine fibers had a significant effect on their physical‐chemical properties. Furthermore, a sustained TCH release from these fiber mats was also observed. Consequently, the electrospun ultrafine fiber mats containing drugs may be used as drug release carriers or made into biomedical devices such as sutures and wound dressings.     

Single-molecule reaction and characterization by vibrational excitation

Controlled chemical reaction of single trans-2-butene molecules on the Pd(110) surface was realized by dosing tunneling electrons from the tip of a scanning tunneling microscope at 4.7 K. The reaction product was identified as a 1,3-butadiene molecule by inelastic electron tunneling spectroscopy. Threshold voltage for the reaction is approximately 365 mV, which coincides with the vibrational excitation of the C-H stretching mode. The reaction was ascertained to be caused by C-H bond dissociation by multiple vibrational excitations of the C-H stretching mode via inelastic electron tunneling process.     

Interaction of C2N2 with clean and oxygen dosed Cu(111) surface studied by AES,ELS and TDS measurements

The adsorption and surface reaction of cyanogen on clean and oxygen covered Cu(111) have been investigated. From electron energy loss measurements, thermal desorption spectroscopy and electron beam effects in Auger spectroscopy, it is proposed that cyanogen adsorbs dissociatively on Cu(111) at 300 K. The activation energy for the desorption was calculated to be 180 kJ/mol. Cyanogen adsorption onto oxygen predosed Cu(111) is inferred to produce the NCO surface species. This interpretation was aided by data of electron energy loss measurements and from HNCO adsorption onto Cu(111) at 300 K. A reaction began in the co-adsorbed layer above 400 K, yielding CO₂ and N₂.     

Synthesis and Characterization of pH- and Temperature-sensitive Hydrogels of Poly (Styrene-alt-Maleic Anhydride)-co-Pluronic for Drug Release

A pH- and temperature-sensitive hydrogel of poly(styrene-alt-maleic anhydride) -co-Pluronic P123 (PSMA-P123) was prepared by the reaction of anhydride groups (MA) on PSMA with the hydroxyl groups on Pluronic (triblock polyethylene oxide-co-polypropylene oxide-co-polyethylene oxide, HO(CH₂CH₂O)₂₀(CH₂CH(CH₃)O)₇₀ (CH₂CH₂O)₂₀OH). The effect of proportions between PMSA and P123 on the gel fraction was determined. The effects of pH value and temperature on swelling ratio of the hydrogels were evaluated. Scanning electron microscopy was used to observe the morphology of the hydrogels. Differential scanning calorimetry was employed to characterize the thermo-sensitivity of the hydrogel. The drug-release behavior of the hydrogels was investigated by using chloromycetin as a model drug. The effect of temperature and pH on the release of chloromycetin from the hydrogels was studied. These results showed that PSMA-P123 hydrogels, being pH- and temperature-sensitive and reversible, appeared to be of potential for biomedical materials, especially for drug release applications.     

Preparation and characterization of L-Leucine-modified amphiprotic bifunctional mesoporous SBA-15 molecular sieve as a drug carrier for ribavirin

In this study, an amphiphilic bifunctional mesoporous SBA-15 material (AMPBIF-SBA-15) was synthesized through post-synthesis method as a drug carrier. Ribavirin was selected as the model drug and whose release from both unmodified and functionalized SBA-15 was evaluated in four media solutions with different pH or ionic strength. The release process indicated that AMPBIF-SBA-15 was a pH-sensitive drug carrier, which showed a phased low-release effect to ribavirin in the simulated body fluid (PBS, pH 7.4) solution. The materials were further characterized by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption measurements and elemental analysis. This study provided a novel drug carrier for ribavirin to improve curative effect of ribavirin.     

Simple and sensitive spectrophotometric methods for determination of amantadine hydrochloride

Three simple and sensitive spectrophotometric methods (A–C) for determination of amantadine hydro-chloride have been developed and validated. The first method (A) is based on the oxidation of the drug by ammonium molybdate. The second method (B) was based on the charge-transfer complexation reaction between the amantadine base as an electron donor and iodine as a σ-acceptor. The third method (C) is based on the reaction of N-alkylvinylamine formed from the interaction of the free amino group in amantadine molecule and acetalde-hyde with chloranil to give colored vinylamino-substituted benzoquinone. The colored products of these reactions were measured at their corresponding maximum absorption peaks. Different variables affecting the reactions were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients 0.9993–0.9998 were found between the reading and the corresponding concentration of the drug in the range 2–90 μg·ml⁻¹. The limits of detection ranged from 0.16 to 1.91 μg·ml⁻¹. The precision of the methods was satisfactory: the values of relative standard deviation did not exceed 1.63%. The proposed methods were successfully applied to the analysis of amantadine HCl in its capsules with good accuracy and precision; the label claim percentages ranged from 99.8 to 100.5 ± (0.52–1.22) %. The results obtained by the proposed spectrophotometric methods were comparable with those obtained by the official method. Published in Zhurnal Prikladnoi Spektroskopii, Vol. 73, No. 6, pp. 707–712.     

Preparation and in vitro evaluation of an ultrasound-triggered drug delivery system: 10-hydroxycamptothecin loaded PLA microbubbles

10-Hydroxycamptothecin (HCPT) loaded PLA microbubbles, used as an ultrasound-triggered drug delivery system, were fabricated by a double emulsion-solvent evaporation method. The obtained microbubbles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and confocal laser scanning microscope (CLSM). In addition, the effect of diagnostic ultrasound exposure on BEL-7402 cells combined with HCPT-loaded PLA microbubbles was evaluated using cytotoxicity assay, CLSM and flow cytometry (FCM). It was found that the HCPT-loaded PLA microbubbles showed smooth surface and spherical shape, and the drug was amorphously dispersed within the shell and the drug loading content reached up to 1.69%. Nearly 20% of HCPT was released upon exposure to diagnostic ultrasound at frequency of 3.5 MHz for 10 min. Moreover, HCPT fluorescence in the cells treated only with the HCPT-loaded PLA microbubbles was discernible, but less intense, while those treated with the microbubbles in conjunction with ultrasound exposure was evident and intense, indicating an increased cellular uptake of HCPT by ultrasound exposure. Cytotoxicity test on BEL-7402 cells indicated that the HCPT-loaded PLA microbubbles combined with ultrasound exposure were more cytotoxic than the microbubbles alone. The results suggest that the combination of drug loaded PLA microbubbles and diagnostic ultrasound exposure exhibit an effective intracellular drug uptake by tumor cells, indicating their great potential for antitumor therapy.     

氟罗沙星荷移络合物在胶束体系中的紫外光谱特性及应用

采用紫外光谱法研究了π电子受体四氯对苯醌(TCBQ)与电子供体氟罗沙星的荷移反应,结果表明,氟罗沙星与TCBQ在十二烷基硫酸钠(SDS)胶束体系中能形成稳定的荷移反应络合物,使其吸光度明显增强。据此建立了氟罗沙星简单、快速、准确和灵敏的分析方法。氟罗沙星浓度在0. 6～24 mg·L-1范围内符合比尔定律。r= 0.999 3。荷移络合物在326 nm处的表观摩尔吸光系数为3.3×104 L·mol-1·cm-1。本方法用于片剂中氟罗沙星含量的测定, 其回收率为99.3%～99.8%, 相对标准偏差为0.9%～2.3%。     

Spectrophotometric and spectrofluorimetric determinations of veterinary drug enrofloxacin in pharmaceutical formulation

Four simple, sensitive spectrophotometric and spectroflourimetric methods (A-D) for the determination of veterinary drug enrofloxacin (ENFX) in pharmaceutical formulation have been developed. Method (A) is based on formation of ternary complex of ENFX with Pd(II) in presence of methyl cellulose as surfactant and acetate-HCl buffer pH 4.0. Method (B) is based on the oxidation of ENFX with alkaline potassium permanganate to give a green colored reaction product. The reaction was monitored spectrophotometrically by measuring the absorbance of the reaction product at 604 nm. Method (C) is based on the oxidation of the ENFX by a known excess of potassium permanganate in acid medium and subsequent determination of unreacted oxidant by reacting it with safronine O (SFO). Method (D) is based on the chelation of ENFX with Zr(IV), to produce fluorescent chelate. At the optimum reaction conditions, the drug/metal chelate showed excitation maxima at 280 nm and emission maxima at 440 nm. The optimum experimental parameters for the reaction have been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drug in pharmaceutical preparations with good recoveries. The procedures were accurate, simple and suitable for quality control application.     

Controlled Release of an Antihypertensive Drug through Interpenetrating Polymer Network Hydrogel Tablets of Tamarind Seed Polysaccharide and Sodium Alginate

The application of interpenetrating polymer network (IPN) hydrogel tablets of tamarind seed polysaccharide and sodium alginate for controlled release of a water-soluble antihypertensive drug, propranolol HCl (PPL), was investigated. The IPN tablets loaded with PPL or PPL–resin complex (resinate) were prepared by a wet granulation/covalent cross-linking method. Fourier Transform Infrared Spectroscopic confirmed the cross-linking reaction and IPN formation, while X-ray Diffraction and Scanning Electron Microscopy studies confirmed the amorphous dispersion of the drug within the IPN tablets. The plain drug PPL showed complete release within 1 h, while drug release from the resinate was prolonged for 2.5 h and the IPN matrices showed drug release up to 24 h. The drug release rate from the IPN matrices was affected by polymer concentration and cross-linking time; the higher the cross-linking time, the slower was the drug release. The drug release mechanism was found to be of a non-Fickian type.