Efficient removal of chlortetracycline hydrochloride and doxycycline hydrochloride from aqueous solution by ZIF-67.

ZIF-67 nanoparticles were synthesized by a simple method at room temperature and used to remove chlortetracycline hydrochloride (CTC) and doxycycline hydrochloride (DOX) from water. ZIF-67 was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET) surface area, X-ray photoelectron spectroscopy (XPS), thermogravimetry (TGA) and zeta potential analyzer. The morphology and chemical composition of the synthesized ZIF-67 were characterized. The effects of key parameters such as pH, dosage, temperature, contact time, different initial concentrations and coexisting ions on the adsorption behavior were systematically studied. The results of batch adsorption experiments indicate that the adsorption process conforms to the pseudo-second-order kinetic model and Sips model. At 303K, the removal rates of CTC and DOX at 150 mg/L reached 99.16 % and 97.61 %, and the maximum adsorption capacity of CTC and DOX reached 1411.68 and 1073.28 mg/g, respectively. At the same time, ZIF-67 has excellent stability and reusability. Most importantly, the possible adsorption mechanism is proposed by exploring the changes of SEM, TEM, BET and FT-IR characterization results before and after the reaction, which mainly includes pore filling, electrostatic interaction and π-π interaction. The prepared ZIF-67 has a large specific surface area (1495.967 m2 g-1), achieves a high removal rate within a short time frame, and maintains a high removal rate across a wide pH range. These characteristics make ZIF-67 a potentially promising adsorbent for removing antibiotics from aqueous solutions.

Studies on Sorption and Release of Doxycycline Hydrochloride from Zwitterionic Microparticles with Carboxybetaine Moieties.

The aim of this study was to examine the use of zwitterionic microparticles as new and efficient macromolecular supports for the sorption of an antibiotic (doxycycline hydrochloride, DCH) from aqueous solution. The effect of relevant process parameters of sorption, like dosage of microparticles, pH value, contact time, the initial concentration of drug and temperature, was evaluated to obtain the optimal experimental conditions. The sorption kinetics were investigated using Lagergren, Ho, Elovich and Weber-Morris models, respectively. The sorption efficiency was characterized by applying the Langmuir, Freundlich and Dubinin-Radushkevich isotherm models. The calculated thermodynamic parameters (ΔH, ΔS and ΔG) show that the sorption of doxycycline hydrochloride onto zwitterionic microparticles is endothermic, spontaneous and favorable at higher temperatures. The maximum identified sorption capacity value is 157.860 mg/g at 308 K. The Higuchi, Korsmeyer-Peppas, Baker-Lonsdale and Kopcha models are used to describe the release studies. In vitro release studies show that the release mechanism of doxycycline hydrochloride from zwitterionic microparticles is predominantly anomalous or non-Fickian diffusion. This study could provide the opportunity to expand the use of these new zwitterionic structures in medicine and water purification.

Development of a PVA/PCL/CS-Based Nanofibrous Membrane for Guided Tissue Regeneration and Controlled Delivery of Doxycycline Hydrochloride in Management of Periodontitis: In Vivo Evaluation in Rats.

Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.

In-situ production and activation of H2O2 over hydroxyapatite modified CuFeO2 for self-sufficient heterogeneous photo-Fenton degradation of doxycycline hydrochloride.

The self-sufficient heterogeneous photo-Fenton (SH-PF) system was constructed for doxycycline hydrochloride (DOH) degradation with hydroxyapatite (Hap) modified CuFeO2 (Hap/CuFeO2) composites through H2O2 in-situ production. The modification of Hap could improve the specific surface area, visible-light response, light conversion efficiency, photoelectron lifetime and oxygen vacancies (OVs) of CuFeO2, which was conducive to H2O2 production and DOH degradation in SH-PF system. Notably, Hap/CuFeO2 fabricated with 0.5 g Hap (Hap/CuFeO2-0.5) displayed more superior performance for DOH degradation compared to other synthesized catalysts. The Hap/CuFeO2-0.5 load and initial solution pH for DOH degradation in SH-PF system were optimized, and the Hap/CuFeO2-0.5 had good reusability and stability. The •OH was the main active species for DOH degradation, and the facilitation effect of •O2- and photoelectrons on DOH degradation was associated with the H2O2 production in the present work. In addition, the capture of photogenerated holes suppressed the recombination of photogenerated carriers, elevating the production of photoelectrons and thereby enhancing H2O2 production and DOH degradation. The degradation pathways for DOH were proposed and the comprehensive toxicities of DOH were relieved after degradation in SH-PF system.

Doxycycline hydrochloride inhibits the progress of malignant rhabdoid tumor of kidney by targeting MMP17 and MMP1 through PI3K-Akt signaling pathway.

OBJECTIVE: To identify therapeutic targets for malignant rhabdoid tumors of kidney (MRTK) and to investigate the effects and underlying mechanism of doxycycline hydrochloride on these tumors. METHODS: Gene expression and clinical data of MRTK were retrieved from the TARGET database. Differentially expressed genes (DEGs) and prognostic-related genes (PRGs) were selected through a combination of statistical analyses. The functional roles of MMP17 and MMP1 were elucidated through RNA overexpression and intervention experiments. Furthermore, in vitro and in vivo studies provided evidence for the inhibitory effect of doxycycline hydrochloride on MRTK. Additionally, transcriptome sequencing was employed to investigate the underlying molecular mechanisms. RESULTS: 3507 DEGs and 690 PRGs in MRTK were identified. Among these, we focused on 41 highly expressed genes associated with poor prognosis and revealed their involvement in extracellular matrix regulatory pathways. Notably, MMP17 and MMP1 stood out as particularly influential genes. When these genes were knocked out, a significant inhibition of proliferation, invasion and migration was observed in G401 cells. Furthermore, our study explored the impact of the matrix metalloproteinase inhibitor, doxycycline hydrochloride, on the malignant progression of G401 both in vitro and in vivo. Combined with sequencing data, the results indicated that doxycycline hydrochloride effectively inhibited MRTK progression, due to its ability to suppress the expression of MMP17 and MMP1 through the PI3K-Akt signaling pathway. CONCLUSION: Doxycycline hydrochloride inhibits the expression of MMP17 and MMP1 through the PI3K-Akt signaling pathway, thereby inhibiting the malignant progression of MRTK in vivo and in vitro.

Adsorption characterization of tetracycline antibiotics on alkali-functionalized rice husk biochar and its evaluation on phytotoxicity to seed germination.

This work presented adsorption characteristics of tetracycline antibiotics (TCs) on KOH-functionalized rice husk biochar pyrolyzed at 700 °C (KBC700) and evaluation on phytotoxicity of TCs-adsorbed aqueous phase to seed germination. Specifically, KBC700 gained eightfold rise in specific surface area by KOH activation. Predominant monolayer chemisorption helped KBC700 control TCs, and spontaneous and exothermic features were identified by thermodynamic studies. KBC700 could efficiently work in a wide pH range (4.5 ~ 9.5), as well as in simulated eutrophic water and co-existing cationic solution. Humic acid exerted negative impact on TCs disposal. Outstanding regeneration capability and stability were also found during adsorption-desorption cycles. Mechanism discussion implied predominant pore filling and π-π interaction accompanied by hydrogen bonding and electrostatic interaction involved in TCs-removal process. Importantly, less phytotoxicity to seed germination was found in TCs-adsorbed aqueous phase. Collectively, these findings contribute to adsorption properties recognition and subsequent application for KOH-modified rice rusk biochar in environmental TCs remediation.

Poly (trimethylene carbonate)/doxycycline hydrochloride films in the treatment of Achilles tendon defect in rats.

Introduction: In this study, Poly (trimethylene carbonate)/Doxycycline hydrochloride (PTMC/DH) films were introduced to repair the Achilles tendon defects for the first time. Methods: (PTMC/DH) films with different DH content of 10, 20, and 30% (w/w) were prepared by solvent casting. The in vitro and in vivo drug release of the prepared PTMC/DH films was investigated. Results: The results of drug release experiments showed that the PTMC/DH films released effective concentrations of doxycycline for more than 7 and 28 days in vitro and in vivo, respectively. The results of antibacterial activity experiments showed diameters of 25.00 ± 1.00 mm, 29.33 ± 1.15 mm, and 34.67 ± 1.53 mm, respectively, for the inhibition zones produced by the release solutions of PTMC/DH films with 10, 20 and 30% (w/w) DH at 2 h, indicating that the drug-loaded films could inhibit Staphylococcus aureus well. After treatment, the Achilles tendon defects have recovered well, as indicated by the more robust biomechanical properties and the lower fibroblast density of the repaired Achilles tendons. Pathology revealed that the pro-inflammatory cytokine, IL-1ß, and the anti-inflammatory factor, TGF-ß1, peaked in the first three days and gradually decreased as the drug was released more slowly. Discussion: These results demonstrated that the PTMC/DH films have great potential for regenerating Achilles tendon defects.

SERS determination and multivariate classification of antibiotics in chicken meat using gold nanoparticle-decorated electrospun PVA nanofibers.

The fabrication of SERS substrate by gold nanoparticle-decorated polyvinyl alcohol electrospun nanofibers which has been used to detect trace sensing of two widely used poultry antibiotics doxycycline hydrochloride and enrofloxacin is demonstrated. The performance of the backscattered Raman signals from the proposed SERS substrate has been initially evaluated with two standard Raman active compounds namely malachite green and rhodamine-6G. The limit of detection of the proposed substrate is estimated to be 7.32 nM. Following this, the usability of the proposed SERS substrate has been demonstrated through the detection of the aforementioned antibiotics in chicken meat samples. The presence of antibiotics in chicken meat sample has been validated with the standard analytical tool of liquid chromatography-mass spectrometry and the results were compared with the proposed sensing technique. Further, principal component analysis has been performed to classify the antibiotics that are present in the field-collected meat samples.

Removal of doxycycline hydrochloride from aqueous solution by rice husk ash using response surface methodology and disposability study.

The huge demand and consumption of DOX, its incomplete metabolism, and complex behavior in atmosphere are causing a great ecological issue, which needs to be solved. In the present study, the suitability of rice husk ash (RHA) for the greater sorption efficiency of DOX antibiotic was investigated. Furthermore, disposability study of exhausted RHA was performed using solidification technique and leachate had undergone toxicity test to evaluate the DOX encapsulation ability. The central composite design under RSM was employed for the design of experiment and optimization of adsorption parameters. RHA was characterized using various techniques such as XRD, SEM (EDX), FTIR, BET, and zeta potential analysis. The influence of various adsorption parameters, like initial DOX concentration (C0), RHA dosage (m), incubation-time period (t), and pH were examined on the performance in terms of DOX elimination % (X1) and adsorptive capacity (mg/g) (X2). At optimized conditions, the obtained X1 and X2 were 98.85% and 17.74 mg/g, respectively. Moreover, the kinetics data suited well to the pseudo-second-order model. Freundlich, Langmuir, and Redlich-Peterson (R-P) isotherm models were applied, out of which Langmuir model best performed under optimized conditions; m = 5 g/L, t = 85.85 min, DOX concentration = 89.73 mg/L, and pH = 6. The bacterial toxicity test of leachate confirmed complete encapsulation of DOX by solidification technique.

Towards BioMnOx-mediated intra/extracellular electron shuttling for doxycycline hydrochloride metabolism in Bacillus thuringiensis.

Doxycycline hydrochloride (DCH) could be continuously removed by Bacillus thuringiensis S622 with the in-situ biogenic manganese oxide (BioMnOx) via oxidizing/regenerating. The DCH removal rate was significantly increased by 3.01-fold/1.47-fold at high/low Mn loaded via the integration of biological (intracellular/extracellular electron transfer (IET/EET)) and abiotic process (BioMnOx, Mn(III) and •OH). BioMnOx accelerated IET via activating coenzyme Q to enhance electrons transfer (ET) from complex I to complex III, and as an alternative electron acceptor for respiration and provide another electron transfer transmission channel. Additionally, EET was also accelerated by stimulating to secrete flavins, cytochrome c (c-Cyt) and flavin bounded with c-Cyt (Flavins & Cyts). To our best knowledge, this is the first report about the role of BioMnOx on IET/EET during antibiotic biodegradation. These results suggested that Bacillus thuringiensis S622 incorporated with BioMnOx could adopt an alternative strategy to enhance DCH degradation, which may be of biogeochemical and technological significance.

Visible-light-driven 3D Bi5O7I/BiOCl microsphere with enhanced photocatalytic capability: Performance, degradation pathway, antibacterium and mechanism.

It is well known that both of the separation efficiency of photogenerated carriers and the response capability to visible light remarkably affect the photocatalytic performance. In the present work, a 3D microsphere of Bi5O7I/BiOCl heterojunction catalyst was synthetised. The synergy of Bi5O7I and BiOCl not only significantly enhances the transfer rate and separation efficiency of carriers, but also heightens light absorption capacity. As-prepared Bi5O7I/BiOCl (40 wt% BiOCl) has a higher degradation efficiency on doxycycline hydrochloride (DC) (90 min, 83.0%) and super high inhibition rate (90 min, 99.92%) on Escherichia coli under visible light, compared to the two monomers. Pollutants DC is finally decomposed into CO2, H2O and small molecule intermediates by generated h+, •OH and •O2-. The effects of reactive radicals follow the order of •OH radicals > h+ radicals ≫ •O2- and e- radicals. The possible structures of intermediates and four possible degradation pathways involved were also discussed. In addition, As-synthetised Bi5O7I/BiOCl has preferable reusability and excellent chemical stability. Biological toxicity experiments also verify that Bi5O7I/BiOCl is a green and environmentally friendly composite material. This strategy provides a green, low-toxic way for the application of traditional type II heterojunction in the fields of environmental remediation and photocatalysis.

Adsorptive decontamination of doxycycline hydrochloride via Prosopis juliflora activated carbon: Parameter optimization and disposal study.

This study deals with the removal of doxycycline hydrochloride (DOX) antibiotic, from aqueous environment by using Prosopis juliflora activated carbon (PJAC). PJAC was synthesized by chemical activation and pyrolysis of Prosopis juliflora. It was characterized by employing Fourier transform infrared spectroscopy (FTIR), scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), X-ray diffraction analysis (XRD), and Brunauer-Emmett-Teller (BET) techniques. The specific surface area, pore volume, and pore diameter were evaluated as 320.45 m2 /g, 0.176 cm3 /g, and 2.65 nm, respectively. Different functional groups (O-H, C-O, C=C, C-N, and C-C) present on PJAC promoted the adsorption of DOX. The influence of various adsorption parameters suggested by central composite design (CCD) model was determined using response surface methodology (RSM), and interactive effects of these were optimized. The thermodynamic and kinetic studies performed at optimized conditions, exhibited that adsorption was spontaneous and endothermic. The experimental data were well described with Langmuir, Redlich-Peterson, and Freundlich isotherm models while kinetics data were well described by pseudo second order. The excellent interactions between the PJAC and DOX resulted maximum adsorption capacity as 57.11 mg/g. The adsorption mechanisms was dominated by π - π interactions and hydrogen bonding. Moreover, almost complete encapsulation of DOX was achieved by stabilization of exhausted PJAC. PRACTITIONER POINTS: A wild harmful plant Prosopis juliflora was used to synthesize a low-cost and eco-friendly bio-sorbent PJAC. Adsorptive ability of PJAC was quantified for adsorption of DOX antibiotic from its aqueous solution. DOX uptake on PJAC was mainly governed by л-л EDA interactions and hydrogen bonding.

Characteristics of Cu(II)-modified aerobic granular sludge biocarbon in removal of doxycycline hydroxide.

In this study, the biocarbon derived from aerobic granular sludge with different nutritive proportions was modified by Cu(NO3)2•3H2O (Cu-BC) to improve its adsorption capacity of doxycycline hydrochloride (DOX). The surface area, pores, functional groups, and element composition of biocarbon were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area, X-ray photoelectron spectrometer, X-ray diffraction (XRD), the X-ray photoelectron spectrometer, and Fourier transform infrared spectrometry (FT-IR), respectively. Effects of DOX concentration, initial pH, and background electrolyte on adsorption effects of composite were analyzed. Furthermore, the adsorption kinetics, isotherm, thermodynamics, and diffusion model were investigated. Results demonstrated that biocarbons which were prepared with aerobic granular sludge under different nutritive proportions presented different performances. The BET specific surface area of Cu-NaAC/AGS-BC was 260.1592 m2/g, and the micropore volume was 0.054101 cm3/g. The BET specific surface area of Cu-GLC /AGS-BC was only 10.6821 m2/g, and the micropore volume was 0.008687 cm3/g. Both kinds of modified biochar contain a large number of oxygen-containing functional groups. The highest adsorption efficiency of Cu-BC could reach 99.54%. The adsorption of DOX on two modified biocarbons conforms to the pseudo-second-order dynamic model and Temkin isothermal model.

Surface-enhanced Raman spectroscopy method for classification of doxycycline hydrochloride and tylosin in duck meat using gold nanoparticles.

This paper investigated on 478 duck meat samples for the identification of 2 kinds of antibiotics, that is, doxycycline hydrochloride and tylosin, that were classified based on surface-enhanced Raman spectroscopy (SERS) combined with multivariate techniques. The optimal detection parameters, including the effects of the adsorption time, and 2 enhancement substrates (i.e., gold nanoparticles as well as gold nanoparticles and NaCl) on Raman intensities, were analyzed using single factor analysis method. The results showed that the optimal adsorption time between gold nanoparticles and analytes was 2 min, and the colloidal gold nanoparticles without NaCl as the active substrate were more conducive to enhance the Raman spectra signal. The SERS data were pretreated by using the method of adaptive iterative penalty least square method (air-PLS) and second derivative, and from which the feature vectors were extracted with the help of principal component analysis. The first four principal components scores were selected as the input values of support vector machines model. The overall classification accuracy of the test set was 100%. The experimental results showed that the combination of SERS and multivariate analysis could identify the residues of doxycycline hydrochloride and tylosin in duck meat quickly and sensitively.

When is it safe to eat different broiler chicken tissues after administration of doxycycline and tylosin mixture?

Residues of veterinary drugs in poultry meat have serious health effects on humans (e.g., antimicrobial resistance, carcinogenicity, and hypersensitivity), which make the control of veterinary drug residues an important parameter in ensuring consumer protection.  This work was performed to quantitatively determine two co-formulated anti-infective veterinary agents, tylosin tartrate (TYT) and doxycycline hydrochloride (DOX) in different tissues of broiler chickens (liver, muscles, and fat) using high performance liquid chromatography. The chicken was treated with the recommended dose of a binary mixture of the drugs (Tydovet). Moreover, the study aimed to estimate the withdrawal time of both drugs in chicken tissues. The analysis was done by solvent extraction and solid-phase extraction for clean-up of samples from the tissue matrix, followed by liquid chromatographic determination of the cited drugs with UV-detection. Residue decline with time was tracked, and both antibiotics were found to be more persistent in liver tissues than other tissues (muscle and fat). The effect of freezing and cooking was investigated on tissue residue levels. While freezing had little effect on the concentration of both antibiotics; cooking, as anticipated, led to a marked decline. Therefore, it is recommended to pay attention to the proper withdrawal periods before marketing to ensure the hygienic suitability of broilers edibles for safe human consumption. PRACTICAL APPLICATION: This novel study measures tylosin and doxycycline residues simultaneously in different tissues (muscle, fat, and liver) after administration of Tydovet powder to the broiler chicken. Residues in fat persisted for a longer time than in muscle in case of TYT, whereas the reverse was noticed in DOX.

Paired wavelength relevance as spectrophotometric strategy for evaluation the potency of medicine affecting human health.

Paired wavelength relevance as spectrophotometric strategy was carried for simultaneous analysis of unresolved bands of doxycycline hydrochloride (DOX) and tylosin tartrate (TYT) as an example of veterinary binary mixture. These methods based on the relation between two points on the scanned or manipulated spectra (derivative, ratio). The methods using the absorbance difference between two wavelengths namely, dual wavelength (DW), induced dual wavelength (IDW), absorption correction (AC) and advanced absorbance subtraction (AAS) or amplitude difference namely, ratio difference (RD), amplitude subtraction namely, amplitude correction (PC) and advanced amplitude modulation (AAM) as well as amplitude addition namely, derivative ratio (DD1). Calibration graphs are direct relation in the range of (5-40) µg/mL for doxycycline hydrochloride and (5-45) µg/mL for tylosin tartrate. The suggested methods was successfully applied for evaluate the potency of their veterinary medicine that has direct affecting human health. The method has been validated according to the guideline of international conference on Harmonization and parameters like linearity, range, accuracy and precision have been studied. The outcomes were matched statistically with those of the authorized systems; Student's t-test, F-test, and One-way ANOVA, presenting acceptable values and no momentous change with accuracy. The procedures can be considered useful for the quantitative analysis.

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 32 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNPopt) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNPopt, with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNPopt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: development, in-vitro and in-vivo clinical evaluation.

OBJECTIVE: To formulate solid lipid microparticles (SLMs) encapsulating doxycycline hydrochloride (DH) and metronidazole (MT) for the treatment of periodontal diseases. METHODS: SLMs were prepared applying hot homogenization method, using different types of lipids and stabilized with various types and concentrations of surfactants. The optimized formula was subjected to freeze-drying followed by incorporation into poloxamer gel. Microbiological and clinical evaluation of the selected SLMs on patients suffering from periodontal diseases was performed. RESULTS: SLMs could entrap high percentage of both drugs (81.14% and 68.75 % for doxycycline hydrochloride and metronidazole respectively). Transmission electron microscopy images of SLMs showed nearly spherical particles. Freeze-dried SLMs showed satisfactory stability for three months. Combined drugs were molecularly dispersed in SLMs. Incorporation of the freeze-dried SLMs powder in poloxamer gel could control the drugs release for 72 h. In-vivo study revealed effective and safe use of SLMs gel for periodontitis treatment. Significant improvement in both microbiological and clinical parameters was observed as compared to scaling and root planing alone. CONCLUSION: The formulated SLMs gel offers an applicable dosage form that can be injected directly into the periodontal pocket as adjunctive to scaling and root planing.

[Ningmitai Capsules combined with doxycycline hydrochloride for Ureaplasma urealyticumpositive chronic prostatitis].

OBJECTIVE: To investigate the effects of Ningmitai Capsules (NMT) combined with doxycycline hydrochloride (DH) on chronic prostatitis induced by Ureaplasma urealyticum (Uu). METHODS: This randomized controlled trial included 240 male patients with Uupositive chronic prostatitis, treated orally with NMT at 4 capsules tid (n= 35), DH at 100 mg bid (n = 78), and NMT+DH at the corresponding doses (n = 127), respectively, all for 2 successive weeks. At 1 week after drug withdrawl, we conducted routine urine analysis, EPS examination, and drug sensitivity test of the cultured Uu. RESULTS: The positivetonegative rate of Uu was significantly higher in the NMT+DH group than in the NMT and DH groups (89.0% ［113/127］ vs 54.3% ［19/35］ and 71.8% ［56/78］, P< 0.05), so were the cure rate (25.2% vs 20.0% and 20.5%, P< 0.05) and total effectiveness rate (89.0% vs 54.3% and 71.8%, P< 0.05). CONCLUSIONS: The combination of Ningmitai Capsules and doxycycline hydrochloride is more effective than either Ningmitai Capsules or doxycycline hydrochloride used alone in the treatment of Uupositive chronic prostatitis.

Preparation, characterization and pharmacokinetics of doxycycline hydrochloride and florfenicol polyvinylpyrroliddone microparticle entrapped with hydroxypropyl-ß-cyclodextrin inclusion complexes suspension.

In order to effectively control the bacterial pneumonia in pigs, doxycycline hydrochloride (DoxHcl) and florfenicol (FF) microparticle suspension together with inclusion complexes was prepared by using hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as host molecules, polyvinylpyrroliddone (PVP) as polymer carriers and hydroxypropyl methyl cellulose (HPMC) as suspending agents. In vitro antibacterial activity, properties, stability and pharmacokinetics of the suspension were studied. The results demonstrated that DoxHcl and FF had a synergistic or additive antibacterial activity against Streptococcus suis, Actinobacillus pleuropneumoniae and Haemophilus parasuis. The size, polydispersity index and zeta potential of microparticles were 1.46 ± 0.06 µm, 0.30 ± 0.02 and 1.53 ± 0.04 mV, respectively. The encapsulation efficiency (EE) of DoxHcl and FF was 45.28% ± 3.30% and 89.69% ± 2.71%, respectively. The re-dispersed time and sedimentation rate of the suspension were 1 min and 1. The suspension went through the 9-gage needle smoothly with withdrawal volume of 9.12 ± 0.87 mL/min. The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration to pig, DoxHcl and FF could maintain over 0.15 µg/mL for 72 h. Compared to the control injection, the suspension increased the elimination half-life (T½ke) as well as mean residence time (MRT) of DoxHcl from 5.73 to 9.77 h and from 12.02 to 18.81 h, and those of FF from 12.02 to 26.19 h and from 12.02 to 28.16 h, respectively. The suspension increased the bioavailability of DoxHcl and FF by 1.74 and 1.13-fold, respectively. These results suggest that the compound suspension is a promising formulation for pig pneumonia therapy.