高强度聚焦超声在药物控制释放的应用及进展

高强度聚焦超声能够以一种非侵入性的方式有效地穿透身体内部组织,聚焦在深层组织中一个很小的空间区域内,产生很强的声能,这些能量被组织吸收引起局部温度的升高。当温度到达热敏脂质体的相变温度时,磷脂烷基链构象的会发生改变,导致脂质体的通透性增强,从而能够促进药物的释放。因此,高强度聚焦超声可以被用作外源刺激控制体内特定位置热敏脂质体的药物释放。本文对高强度聚焦超声在药物控制释放领域的应用及进展进行综述。     

Artificial cationic peptides that increase nuclease resistance of siRNA without disturbing RNAi activity

Properties of cationic peptides bearing amino or guanidino groups with various side chain lengths that bind to double stranded RNAs (dsRNAs) were investigated. Peptides with shorter side chain lengths effectively bound to dsRNAs (12mers) increasing their thermal stability. NMR measurements suggested that the cationic peptide binds to the inner side of the major groove of dsRNA. These peptides also increased the thermal stability of siRNA and effectively protected from RNase A digestion. On the other hand, both peptides containing amino groups and guanidine groups did not disturb RNAi activity.     

Effect of curcumin-nanoemulsion associated with photodynamic therapy in breast adenocarcinoma cell line

Curcumin, a natural compound has several antineoplastic activities and is a promising natural photosensitizer used in photodynamic therapy. However, its low solubility in physiological medium limit the clinical use of curcumin. This study aimed to analyze the action of curcumin-nanoemulsion, a new and well-designed Drug Delivery System (DDS+) molecule, used as a photosensitizing agent in photodynamic therapy in an in vitro breast cancer model, MCF-7 cells. The empty nanoemulsion fulfils all necessary requirements to be an excellent DDS. Furthermore, the use of curcumin-nanoemulsion in photodynamic therapy resulted in a high phototoxic effect after activation at 440?nm, decreasing to <10% viable tumor cells after two irradiations and increasing the reactive oxygen species (ROS) production. The use of curcumin-nanoemulsion associated with photodynamic therapy resulted in an increase in the levels of caspase 3/7 activity for the studied MCF-7 cell model, indicating that this therapy triggers a cascade of events that lead to cell death, such as cellular apoptosis. In conclusion, curcumin-nanoemulsion proved to be efficient as a photosensitizing agent, had phototoxic effects, significantly decreased the proliferation of MCF-7 cells and stimulating the ROS production in combination with photodynamic therapy, so, this formulation has a great potential for use in treatment of breast cancer.     

Quantitative determination of the antitumor alkyl ether phospholipid edelfosine by reversed-phase liquid chromatography-electrospray mass spectrometry: application to cell uptake studies and characterization of drug delivery systems

Edelfosine is a synthetic alkyl ether phospholipid that represents a promising class of antitumor agents. However, analytical methods to measure these type compounds are scarce. The lack of a reliable methodology to quantify edelfosine is a major problem in ongoing and scheduled preclinical and clinical trials with this drug. We evaluated the applicability of high-performance liquid chromatography-mass spectrometry to determine edelfosine in biological samples and polymeric delivery systems. Sample pre-treatment involved polymer precipitation or cell lysis with methanol. HPLC separation was performed on an Alltima RPC(18) narrow-bore column and edelfosine quantification was done by electrospray ionization mass spectrometry (ESI-MS) using positive ion mode and selected ion monitoring. Assays were linear in the tested range of 0.3-10 microg/ml. The limit of quantification was 0.3 ng/sample in both matrices, namely biological samples and polymeric delivery systems. The interassay precision ranging from 0.79 to 1.49%, with relative errors of -6.7 and 12.8%. Mean extraction recovery was 95.6%. HPLC-ESI-MS is a reliable system for edelfosine analysis and quantification in samples from different sources, combining advantages of full automation (rapidity, ease of use, no need of extensive extraction procedures) with high analytical performance and throughput.     

Protein-encapsulated bio-nanocapsules production with ER membrane localization sequences

Bio-nanocapsules (BNCs) are hollow nanoparticles composed of the L protein of hepatitis B virus (HBV) surface antigen (HBsAg), which can specifically introduce genes and drugs into various kinds of target cells. Although the classic electroporation method has typically been used to introduce highly charged molecules such as DNA, it is rarely adopted for proteins due to its very low efficiency. In this study, a novel approach to the preparation of BNC was established whereby a target protein was pre-encapsulated during the course of nanoparticle formation. Briefly, because of the process of BNC formation in a budding manner on the endoplasmic reticulum (ER) membrane, the association of target proteins to the ER membrane with lipidation sequences (ER membrane localization sequences) could directly generate protein-encapsulating BNC in collaboration with co-expression of the L proteins. Since the membrane-localized proteins are automatically enveloped into BNCs during the budding event, this method can be protect the proteins and BNCs from damage caused by electroporation and obviate the need for laborious consideration to study the optimal conditions for protein encapsulation. This approach would be a useful method for encapsulating therapeutic candidate proteins into BNCs.     

Plasmodium berghei: vaccination of mice against malaria with heat inactivated parasitized blood

Heat inactivated Plasmodium berghei-infected blood acted as a vaccine against P. berghei infection in mice. The heat inactivated blood was noninfective. Intact or splenectomized vaccine-treated mice, as well as P. berghei susceptible mice inoculated with whole blood or homogenized spleens from vaccine-treated animals, did not become infected. A/J, DDS and Carworth CF₁ mice were all protected against P. berghei challenge after vaccination. A/J and DDS mice developed good immunity after a single vaccination injection. Similar levels of immunity were obtained in CF₁ mice after at least two vaccine injections. Immunized mice responded to P. berghei challenge with mild anemias and low level parasitemias. Resolution of infection occurred between the first and third weeks after challenge. Nonvaccinated mice developed progressive anemia and parasitemia during the same time period. The immunity appears to be caused by P. berghei antigens; it could not be induced by homologous or heterologous noninfected red blood cells, P. gallinaceum-infected blood or Freund's Complete Adjuvant.     

Solvation-Driven Grain Boundary Passivation Improving the Performance of Perovskite Solar Cells

The efficiency of perovskite solar cells (PSCs) is hindered by substantial defects within the grain boundaries (GBs) of polycrystalline perovskite films. Conventional post-treatment strategies struggle to precisely repair these defects at GBs. Here, a targeted grain boundary passivation strategy through solvent effects by incorporating symmetrical biphenyl molecules is proposed, 4,4′-diaminodiphenyl sulfone (DDS) and 4,4′-sulfodiphenol (SDP), aiming to mitigate defects at GBs and optimize energy level arrangements through their electric dipole effects. Compared to the pristine device, the SDP-modified device exhibits significant improvements, including a champion efficiency of 24.39% and an impressive fill factor, along with excellent operation stability. This work provides an effective and straightforward solution for improving the performance of PSCs.     

复合凝乳酶对功能性消化不良儿童营养状态和摄食行为的影响

目的:观察复合凝乳酶胶囊对不同亚型功能性消化不良儿童临床表现、营养状态和摄食行为的影响及安全性。方法:以2017年8月至2018年9月在湖北省妇幼保健院儿童消化内科就诊的功能性消化不良(Functional dyspepsia,FD)儿童为研究对象进行问卷调查,观察治疗前和复合凝乳酶治疗2 w后患儿临床症状变化及药物相关不良反应的发生情况,监测患儿身高和体重,进行膳食情况的调查。结果:共163例儿童纳入研究,发生餐后不适综合征(Postprandial distress syndrome, PDS)66例,上腹痛综合征(Epigastric pain syndrome, EPS)97例。治疗前,PDS组儿童症状总分明显高于EPS儿童(6.9±2.7 vs 3.6±1.7,t=5.90,P=0.00)。PDS组儿童WAZ、WHZ、HAZ、身高别体质量Z值(weight for height Z score,WHZ)、年龄别身高Z值(height for age Z score,HAZ)、年龄别体质量Z值(weight for age Z score,WAZ)、体质量指数(body mass index,BMI)、膳食多样化分数(Dietary diversity score, DDS)均明显低于EPS组(P均0.05)。治疗2 w后,PDS儿童症状总分明显降低(P=0.00),改善程度依次为:厌食早饱腹痛嗳气恶心腹胀。EPS儿童症状总分无明显变化(P=0.11)。PDS儿童WAZ、WHZ、DDS均有明显升高(P均0.05)。EPS儿童DDS无明显变化(t=0.22,P=0.30)。研究期间未见明显药物相关不良反应。结论:复合凝乳酶胶囊可改善PDS患儿的临床症状、营养状态和膳食多样性,且安全性高。     

Physicochemical properties and in vitro intestinal permeability properties and intestinal cell toxicity of silica particles,performed in simulated gastrointestinal fluids

Background

Amorphous silica particles with the primary dimensions of a few tens of nm, have been widely applied as additives in various fields including medicine and food. Especially, they have been widely applied in powders for making tablets and to coat tablets. However, their behavior and biological effects in the gastrointestinal tracts associated with oral administration remains unknown.

Methods

Amorphous silica particles with diameters of 50, 100, and 200 nm were incubated in the fasted-state and fed-state simulated gastric and intestinal fluids. The sizes, intracellular transport into Caco-2 cells (model cells for intestinal absorption), the Caco-2 monolayer membrane permeability, and the cytotoxicity against Caco-2 cells were then evaluated for the silica particles.

Results

Silica particles agglomerated in fed-state simultaneous intestinal fluids. The agglomeration and increased particles size inhibited the particles' absorption into the Caco-2 cells or particles' transport through the Caco-2 cells. The in vitro cytotoxicity of silica particles was not observed when the average size was larger than 100 nm, independent of the fluid and the concentration.

Conclusion

Our study indicated the effect of diet on the agglomeration of silica particles. The sizes of silica particles affected the particles' absorption into or transport through the Caco-2 cells, and cytotoxicity in vitro, depending on the various biological fluids.

General significance

The findings obtained from our study may offer valuable information to evaluate the behavior of silica particles in the gastrointestinal tracts or safety of medicines or foods containing these materials as additives.