Construction and evaluation in vitro and in vivo of tedizolid phosphate loaded cationic liposomes.

First, the SA-TDZA-Lips were prepared by reverse-phase evaporation method. Then, the drug release behaviour was evaluated by dynamic membrane dialysis in vitro and the preliminary safety was evaluated by haemolysis method. Finally, with tedizolid phosphate injection (TDZA-Inj) and tedizolid phosphate loaded liposomes (TDZA-Lips) as the control groups, the pharmacokinetic characteristic and tissues distribution of SA-TDZA-Lips were evaluated after intravenous injection. As a result, the stearylamine modified tedizolid phosphate liposomal delivery system was constructed successfully and the particle size was 194.9 ± 2.93 nm. The encapsulation efficiency (EE) was 53.52 ± 2.18%. The in vitro release of SA-TDZA-Lips was in accordance with Weibull equation. And there was no haemolysis happened, which indicated good preliminary safety for injection. The results of pharmacokinetics showed that the t1/2ß increased by 0.74 times and 0.51 times higher than that of TDZA-Inj group and TDZA-Lips group, respectively. The MRT of SA-TDZA-Lips was 1.30 and 1.09 times higher than that of TDZA-Inj group and TDZA-Lips group, respectively. The AUC was 2.40 times and 0.23 times higher than that of TDZA-Inj group and TDZA-Lips group, respectively. The tissue distribution results showed that the relative uptake rate (Re) of TDZA in the lung was 1.527, which indicated the targeting. In conclusion, the SA-TDZA-Lips prepared in this study had several advantages like positive charge, strong cell affinity, prolonged circulation time in vivo, sustained release effect, and increased drug concentration in lungs. All advantages above provided significant clinical value of application for the treatment of bacterial pneumonia with tedizolid phosphate.

Tamibarotene-Loaded PLGA Microspheres for Intratumoral Injection Administration: Preparation and Evaluation.

Tamibarotene (Am80) has good curative effect on advanced hepatocellular carcinoma (HCC). To improve the therapeutic efficacy furtherly, we prepared tamibarotene-loaded PLGA microspheres (Am80-PLGA-MS) for intratumoral injection. Firstly, Am80-PLGA-MS were prepared by emulsion-solvent evaporation method. Subsequently, microspheres were characterized by particle size analysis, drug loading (DL), and entrapment efficiency (EE). Finally, the drug release characteristics in vitro, pharmacokinetic, and pharmacodynamics were studied separately. According to results obtained, microspheres were spherical with a uniform particle size 7.04 ± 0.03 µm and its EE and DL were 82.23 ± 0.74 and 11.74 ± 0.11%, respectively. In vitro, Am80-PLGA-MS can release drug for 14 days and its release behavior was fitted with the Higuchi equation. In pharmacokinetic studies, the t1/2ß, MRT, and AUC of microspheres were 15.43-fold, 8.62-fold, and 9.98-fold those of Am80 solution, respectively, which revealed that the utilization of drug was improved obviously. The pharmacodynamics studies showed that the tumor doubling time, growth inhibition rate, and specific growth rate of tumor of Am80-PLGA-MS were 1.34 times, 2.63 times, and 0.72 times those of drug solution, respectively, indicating that the inhibitory effect on tumor by the microspheres was significantly improved. In summary, Am80-PLGA-MS are promising carrier to enhance the inhibitory effect on tumor, which will provide significantly clinical value for treatment of HCC.

Preparation and Evaluation of Artemether Liposomes for Enhanced Anti-Tumor Therapy.

The aim of the study was to design liposomes (Lips) of artemether (ARM), a plant-derived drug for treatment of metastatic tumors, for the intravenous delivery. The ARM-Lips were prepared using ethanol injection method. Based on the optimization of formulation with single-factor experiments, ARM-Lips were spherical with a uniform particle size (187.3 ± 1.83) nm and its EE and DL were (94.49 ± 1.18)% and (10.94 ± 0.10)%, respectively. The in vitro drug release characteristics of ARM-Lips possessed a sustained release characteristic, and their behavior was in accordance with the first-order kinetics equation. In vivo, after intravenous injection to mice, the t1/2ß, MRT, and AUC of ARM-Lips were 8.38-, 3.38-, and 3.11-fold those of ARM solution (ARM-Sol), respectively. In the pharmacodynamics studies, the tumor doubling time, growth inhibition rate, and specific growth rate of tumor of ARM-Lips were 1.97 times, 1.54 times, and 0.51 times those of ARM-Sol, respectively, which indicated that the anti-tumor effect of ARM-Lips was significantly stronger than that of ARM-Sol. These encouraging results revealed that ARM-Lips would serve as an efficient carrier for ARM for increasing therapeutic efficacy on tumor.

Canine retraction and anchorage loss self-ligating versus conventional brackets: a systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review is to identify and review the orthodontic literature with regards to assessing possible differences in canine retraction rate and the amount of antero-posterior anchorage (AP) loss during maxillary canine retraction, using conventional brackets (CBs) and self-ligating brackets (SLBs). METHODS: An electronic search without time or language restrictions was undertake in September 2014 in the following electronic databases: The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, Web of science. We also searched the reference lists of relevant articles. Quality assessment of the included articles was performed. Two of the authors were responsible for study selection, validity assessment and data extraction. RESULTS: Six studies met the inclusion criteria, including 2 randomized controlled trials and 4 control clinical studies. One was assessed as being at low risk of bias. Five trials were assessed as being at moderate risk of bias. The meta-analysis from 6 eligible studies showed that no statistically significant difference was observed between the 2 groups in the rate of canine retraction and loss of antero-posterior anchorage of the molars. CONCLUSION: There is some evidence from this review that both brackets showed the same rate of canine retraction and loss of antero-posterior anchorage of the molars. The results of the present systematic review should be viewed with caution due to the presence of uncontrolled interpreted factors in the included studies. Further well-designed and conducted randomized controlled trials are required, to facilitate comparisons of the results.

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome.

The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 individuals, for both the tongue dorsum (n = 2017) and saliva (n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 × 10-11). Four of the five associations were well replicated in an independent cohort of 1439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of host genome-microbiome associations including six genome-wide significant associations mutually validated between the two niches. As many of the oral microbiome-associated genetic variants lie near miRNA genes, we tentatively validated the potential of host miRNAs to modulate the growth of specific oral bacteria. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk scores dominated over oral microbiome in predicting risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.