Multidrug nanomedicine is an effective therapeutic approach for the treatment of chronic diseases and cancers. However, co-encapsulation and release of drug combination at a fixed ratio by nanoparticles, particularly for long acting ocular formulations, remains challenging. Herein, poly (lactic-co-glycolic acid) nanoparticles ratiometrically co-encapsulating hydrophilic dual drugs, mitomycin C and doxorubicin, was obtained (D/M PLGANPs) by combining microfluidics and the Design of Experiments approaches. The formulation variable of lactide-to-glycolide ratios (L/G 50:50, 75:15 and 85:15) was used to achieve fast, medium and slow drug release rates of D/M PLGANPs. The dissolution of D/M PLGANPs in simulated intraocular fluid exhibited sustained release of dual drugs at the fixed ratio over 7 days, and analysis using the Korsmeyer-Peppas model showed mechanism of drug release to be governed by diffusion. More importantly, in human lens epithelial cells, the drug release rate was negatively correlated with drug potency. The slower drug release from D/M PLGANPs led to lower efficacy of drug combination against pathogenesis of cellular migration and proliferation, the key pathogenic processes of capsular opacification after cataract surgery. Compared to fast (L/G 50:50) and medium (L/G 75:15) drug release rate of D/M PLGANPs, the slow release formulation (L/G 85:15) exhibited the least cellular uptake of the dual drugs and the ratio of drug combination was not maintained intracellularly. The present study implicates the potential of using microfluidics for synthesizing polymeric nanoparticles of ratiometric drug combination and highlights the drug release rate as the critical determinant of efficacy for the long-acting nanomedicine design.

In this paper, a pelletizing method has been researched to enhance the subsequent iron-making process applying Guisha limonite, with advantages including large reserves and low price. The purpose is to provide an alternative for the sinter, thus reducing the greenhouse gas emission during the iron-making process. The response surface method is used to optimize the experimental design of the pelleting process. A multivariate regression model for estimating the compressive strength of pellets was developed using Box-Behnken experimental methodology, where the relevant factors were the roasting temperature, pellet diameter, and bentonite content. The maximum influencing factors of each experimental design response are determined using analysis of variance (ANOVA). Under optimum conditions, the compressive strength of pure limonite pellets is 2705 N, similar to the response goal value of 2570.3 N, with a relative error of 5.20%. Since the high-grade iron ore resources are depleted, the comprehensive utilization of ore resources is becoming increasingly important. The aim of this paper was to provide a valuable technical foundation for lignite pellet-roasting processes in the iron and steel industries, since steel companies is increasing its imports of Guisha limonite.

[This corrects the article DOI: 10.3389/fphar.2017.00966.].

Accurate analysis of all of the impurities present in a substance is critical for controlling the impurity profiles of drugs. Penicillins can easily yield a formidable array of degradation-related impurities (DRIs) with significantly different polarities and charge properties, which renders identifying each one a complicated matter. In this work, phenoxymethylpenicillin potassium (Pen V) was selected to find a way to quickly establish a robust analysis method for the impurity profiling of penicillin. Based on the analytical quality by design (AQbD) concept and the degradation mechanism of the drug, structures of all of the DRIs were first proposed. Then Pen V and its detected DRIs were separated and identified by liquid chromatography-tandem mass spectrometry method (LC-MS). Characteristic fragment ions and mass fragmentation process of Pen V and its detected DRIs were summarized. In addition, a quantitative structure-retention relationship (QSRR) model was constructed to predict the retention times of undetected impurities and to evaluate whether the chromatographic system can separate them. Finally, a stability-indicating high-performance liquid chromatography (HPLC) method was developed that can separate all of the DRIs of Pen V.

Background:Dendrobium officinale, a traditional Chinese medical herb with high value that is widely used in Asia, possesses many positive effects on human health, including anti-chronic inflammation, anti-obesity, and immune modulation properties; however, whether D. officinale has inhibitory effects on postmenopausal osteoporosis remains unknown. Objective: We investigated the effects of D. officinale extract (DOE) on ovariectomy-induced bone loss in vivo and on osteoclastogenesis in vitro. Methods:In vivo, female rats were divided into a sham-operated (sham) group and five ovariectomized (OVX) subgroups: OVX with vehicle (OVX), OVX with Xian-Ling-Gu-Bao capsule (240 mg/kg body weight/day), and OVX with low-, medium-, and high-dose DOE (150, 300, and 600 mg/kg body weight/day, respectively). Animals in each group were administered their corresponding treatments for 13 weeks. Body weight, serum biochemical parameters, uterine and femoral physical parameters, bone mineral density (BMD), bone biomechanical properties, and bone microarchitecture were obtained. In vitro, the effects of DOE on osteoclastogenesis were examined using RAW264.7 cells. The effects of DOE on osteoclastogenesis and the expression of osteoclast-specific marker genes and proteins were determined. Results: DOE effectively ameliorated serum biochemical parameters, especially alleviated estradiol (E2) deficiency and maintained calcium and phosphorus homeostasis. DOE improved uterine and femoral physical parameters. In addition, DOE improved femoral BMD and biomechanical properties. DOE significantly ameliorated bone microarchitecture. Moreover, DOE inhibited osteoclastogenesis independent of its cytoxicity and suppressed the expression of osteoclast-specific marker genes and proteins. Conclusion: DOE can effectively prevent ovariectomy-induced bone loss in vivo and inhibit osteoclastogenesis in vitro.

Design of experiment (DoE) is a statistics-based technique for experimental design that could overcome the shortcomings of traditional one-factor-at-a-time (OFAT) approach for protein purification optimization. In this study, a DoE approach was applied for optimizing purification of a recombinant single-chain variable fragment (scFv) against type 1 insulin-like growth factor receptor (IGF-1R) expressed in Escherichia coli. In first capture step using Capto L, a 2-level fractional factorial analysis and successively a central composite circumscribed (CCC) design were used to identify the optimal elution conditions. Two main effects, pH and trehalose, were identified, and high recovery (above 95%) and low aggregates ratio (below 10%) were achieved at the pH range from 2.9 to 3.0 with 32-35% (w/v) trehalose added. In the second step using cation exchange chromatography, an initial screening of media and elution pH and a following CCC design were performed, whereby the optimal selectivity of the scFv was obtained on Capto S at pH near 6.0, and the optimal conditions for fulfilling high DBC and purity were identified as pH range of 5.9-6.1 and loading conductivity range of 5-12.5 mS/cm. Upon a further gel filtration, the final purified scFv with a purity of 98% was obtained. Finally, the optimized conditions were verified by a 20-fold scale-up experiment. The purities and yields of intermediate and final products all fell within the regions predicted by DoE approach, suggesting the robustness of the optimized conditions. We proposed that the DoE approach described here is also applicable in production of other recombinant antibody constructs.