纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Freeze-drying and mechanical redispersion of aqueous PEDOT:PSS

Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films are attracting famous applications in antistatic coating, energy storage and conversion, printed electronics, and biomedical fields due to their conductivity, optical transparency and flexibility. However, PEDOT:PSS has poor dispersion stability during long-term storage and transport. Moreover, the dried PEDOT:PSS films are insoluble in any solvent and cannot be redispersed again. In comparison to bake drying, here, a feasible strategy to achieve mechanically redispersed PEDOT:PSS with the help of freeze-drying process was reported. The redispersed PEDOT:PSS can recover not only the initial characters such as pH, chemical composition, viscosity, and particle size under similar solid contents, but also conductivity and surface morphology of treated films. In addition, the treated film exhibits self-healing properties similar to pristine film in terms of mechanical and electrical properties. This technology enables reuse and overcomes the technical problems of PEDOT:PSS dispersion, realizing real-time processing to meet variable applications.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

Ocular conditions and dry eye due to traditional and new forms of smoking: A review

Addiction to cigarette smoking has high prevalence rates recorded worldwide. Smoking has been linked to several life-threatening systemic conditions such as cancer, heart attack and stroke, in addition to a range of ocular pathologies. In recent years, electronic cigarettes (EC) have emerged as alternatives to smoking. ECs are nicotine delivery devices which produce an aerosol by heating, rather than combusting, a liquid which contains nicotine, flavours and preservatives. This review focuses on the association of traditional and new forms of smoking with dry eye disease, contact lens wear and four other common ocular diseases: cataract, age-related macular degeneration, glaucoma and Graves’ ophthalmopathy. It is concluded that smoking and vaping appear as a risk factor for the aforementioned ocular conditions. An evidence-based, clear link between cigarette smoking, or EC vaping and ocular problems is yet to be discovered.     

Mathematical modeling of growth of Salmonella spp. and spoilage microorganisms in raw oysters

The main objective of this study was to develop the primary and secondary models to describe the growth kinetics of Salmonella as well as background microorganisms in raw, shucked oysters. Samples, inoculated with a cocktail of two Salmonella serotypes, S. Typhimurium (CICC22956) and S. Enteritidis (CICC21482), were incubated at 4, 8, 12, 16, 20, 25, 30, 33, 37, 40, and 43 °C. Growth of Salmonella was observed at all temperatures, except at 4 °C. The background microorganisms grew at all temperatures. All growth curves clearly exhibited lag, exponential and stationary phases, and were analyzed using the Huang growth model. Three secondary models (Ratkowsky square-root, Huang square-root, and Cardinal parameter models) were compared for evaluating the effect of temperature on bacterial growth rates. Data analysis was performed using IPMP 2013, a free predictive microbiology software tool developed by the USDA ARS.The Cardinal parameters model underestimated the specific rates of the microorganisms at low temperatures. The Huang square-root model was more suitable than the Ratkowsky square-root model for describing the effect of temperature on growth of Salmonella, while the Ratkowsky square-root model, on the other hand, was more suitable for background microorganisms. For both Salmonella and background microorganisms, the logarithms of the lag phase were expressed as linear functions of the logarithms of specific growth rates. The results of this study can be used by the food retailers and regulatory agencies to estimate the microbial shelf-life of raw, shucked oysters.     

Automatic generation of variants depending on changes of product properties in a flexible manufacturing environment

Competition forces manufacturing systems to be flexible and to increase product variety and process complexity. These tasks depend on the flexible design of a bill of materials (BOM), one of the most important inputs in manufacturing planning and control systems. Product variety forces systems to generate BOMs with regard to product properties through a BOM pattern. A variant bill of materials provides a structure to manage product variability. In this study, an algorithm is designed to build a BOM pattern using computer-aided design and computer-aided manufacturing (CAD/CAM) data, and another algorithm is designed to generate variants with regard to product specifications. Genetic algorithm is used to generate new products to provide high product variability for testing algorithms. After the test, both algorithms are applied to a real industry problem. The BOM pattern is built automatically using CAD/CAM data, and variants are generated with regard to the pattern, and the results are discussed.     

Stability of probiotic Lactobacillus plantarum in dry microcapsules under accelerated storage conditions

This study investigated the stability of freeze dried and fluid bed dried alginate microcapsules coated with chitosan containing model probiotic bacteria, Lactobacillus plantarum, during storage for up to 45 days at different water activities (0.11, 0.23, 0.40 and 0.70) and temperatures (4, 30 and 37 °C). The loss in cell viability was around 0.8 log in the case of fluid bed drying and around 1.3 in the case of freeze drying, with the former method resulting in dried capsules of smaller size (~ 1 mm vs 1.3 mm), more irregular shape, and with a rougher surface. In both cases, the water activity and water content were less than 0.25 and 10% w/w, respectively, which favours high storage stability. The storage stability studies demonstrated that as the water activity and temperature decreased the survival of the dried encapsulated cells increased. Considerably better survival was observed for fluid bed dried encapsulated cells compared to freeze dried encapsulated cells and freeze dried free cells with 10% sucrose (control), and in some cases, e.g. at 4 and 30 °C at water activities of 0.11, 0.23 and 0.40, there was more than 1 log difference after 45 days, with concentrations higher than 10⁸ CFU/g after 45 days of storage. The results indicate that fluid bed drying is an effective and efficient manufacturing method to produce probiotic containing capsules with enhanced storage stability.     

Heterometallic sulfide cluster [Ag6Sn6S20]10 −: Solvothermal syntheses and characterizations of silver thiostannates with lanthanide complex counter cations

Novel organic hybrid silver thiostannates [Hen]₄[Ln(en)₄]₂[Ag₆Sn₆S₂₀]·3en (Ln = Er, 1; Tm, 2; Yb, 3) were prepared by the reactions of Ln₂O₃, Ag, Sn and S in ethylenediamine (en) under solvothermal conditions. Six SnS₄ tetrahedra and six AgS₃ triangles are connected into the heterometallic sulfide cluster [Ag₆Sn₆S₂₀]^10 − via edge-sharing. In the [Ag₆Sn₆S₂₀]^10 − cluster, a hexanuclear Ag₆S₆ core is enclosed by two Sn₃S₁₀ fragments. The Ag₆S₆ core is the first As–S cluster stabilized by inorganic SnS₄ ligands. In 1–3, all Ln^3 + ions are in 8-fold coordination environments that involved four bidentate en ligands, forming bicapped trigonal prisms. Compounds 1–3 show well-defined absorption edges with band gaps in the range of 2.18–2.47 eV.