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Nanocrystal technology for drug formulation and delivery

Tzu-Lan CHANG, Honglei ZHAN, Danni LIANG, Jun F. LIANG

《化学科学与工程前沿（英文）》 2015年第9卷第1期页码 1-14 doi: 10.1007/s11705-015-1509-3

摘要： With the development of modern technology like high throughput screening, combinatorial chemistry and computer aid drug design, the drug discovery process has been dramatically accelerated. However, new drug candidates often exhibit poor aqueous or even organic medium solubility. Additionally, many of them may have low dissolution velocity and low oral bioavailability. Nanocrystal formulation sheds new light on advanced drug development. Due to small (nano- or micro- meters) sizes, the increased surface-volume ratio leads to dramatically enhanced drug dissolution velocity and saturation solubility. The simplicity in preparation and the potential for various administration routes allow drug nanocrystals to be a novel drug delivery system for specific diseases (i.e. cancer). In addition to the comprehensive review of different technologies and methods in drug nanocrystal preparation, suspension, and stabilization, we will also compare nano- and micro-sized drug crystals in pharmaceutical applications and discuss current nanocrystal drugs on the market and their limitations.

关键词： drug nanocrystal nanotechnology formulation bioavailability stabilizers drug delivery

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Photocatalytic degradation of the acetaminophen by nanocrystal-engineered TiO

Reza Katal, Mohammad Tanhaei, Jiangyong Hu

《环境科学与工程前沿（英文）》 2021年第15卷第2期 doi: 10.1007/s11783-020-1319-9

摘要： Abstract • Photocatalytic activity was improved in TiO2 thin film by rapid thermal annealing. • Photoreactor was designed for TiO2 thin film. • Considerable reusability and durability of prepared photocatalysts were studied. Un-biodegradable pharmaceuticals are one of the major growing threats in the wastewaters. In the current study, TiO2 thin film photocatalysts were designed by nanocrystal engineering and fabricated for degradation of the acetaminophen (ACE) in a photocatalytic reaction under UV light irradiation in batch and continuous systems. The photocatalyst was prepared by sputtering and then engineered by thermal treatment (annealing at 300℃ (T300) and 650℃ (T650)). The annealing effects on the crystallinity and photocatalytic activity of the TiO2 film were completely studied; it was found that annealing at higher temperatures increases the surface roughness and grain size which are favorable for photocatalytic activity due to the reduction in the recombination rate of photo-generated electron-hole pairs. For the continuous system, a flat plate reactor (FPR) was designed and manufactured. The photocatalytic performance was decreased with the increase of flow rate because the higher flow rate caused to form the thicker film of the liquid in the reactor and reduced the UV light received by photocatalyst. The reusability and durability of the samples after 6 h of photocatalytic reaction showed promising performance for the T650 sample (annealed samples in higher temperatures).

关键词： Acetaminophen TiO₂ Thin film Batch Continuous

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Dialdehyde cellulose nanocrystal cross-linked chitosan foam with high adsorption capacity for removal

《化学科学与工程前沿（英文）》 2023年第17卷第7期页码 853-866 doi: 10.1007/s11705-022-2256-x

摘要： The discharge of large amounts of dye-containing wastewater seriously threats the environment. Adsorbents have been adopted to remove these dyes present in the wastewater. However, the high adsorption capacity, predominant pH-responsibility, and excellent recyclability are three challenges to the development of efficient adsorbents. The poly(acryloxyethyl trimethylammonium chloride)-graft-dialdehyde cellulose nanocrystals were synthesized in our work. Subsequently, the cationic dialdehyde cellulose nanocrystal cross-linked chitosan nanocomposite foam was fabricated via freeze-drying of the hydrogel. Under the optimal ratio of the cationic dialdehyde cellulose nanocrystal/chitosan (w/w) of 12/100, the resultant foam (Foam-12) possesses excellent absorption properties, such as high porosity, high content of active sites, strong acid resistance, and high amorphous region. Then, Foam-12 was applied as an eco-friendly adsorbent to remove acid red 134 (a representative of anionic dyes) from aqueous solutions. The maximum dye adsorption capacity of 1238.1 mg∙g^‒1 is achieved under the conditions of 20 mg∙L^‒1 adsorbents, 100 mg∙L^‒1 dye, pH 3.5, 24 h, and 25 °C. The dominant adsorption mechanism for the anionic dye adsorption is electrostatic attraction, and Foam-12 can effectively adsorb acid red 134 at pH 2.5–5.5 and be desorbed at pH 8. Its easy recovery and good reusability are verified by the repeated acid adsorption–alkaline desorption experiments.

关键词： chitosan foam cellulose nanocrystals acid red 134 adsorption

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Taking advantage of drug resistance, a new approach in the war on cancer

null

《医学前沿（英文）》 2018年第12卷第4期页码 490-495 doi: 10.1007/s11684-018-0647-7

摘要：

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer drug resistance genetic screens senescence targeted therapy

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Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

《化学科学与工程前沿（英文）》 2013年第7卷第1期页码 116-122 doi: 10.1007/s11705-013-1310-0

摘要： Polymethacrylic acid (PMA) was synthesized on the backbone of psyllium (Psy) by a microwave assisted method to prepare polymeric grafted materials designated as (Psy- -PMA). Various grades of Psy- -PMA were prepared by changing the degree of grafting from 35%–58% and the materials were then made into tablets. Swelling and biodegradability studies of the tablets were carried out. Acetyl salicylic acid was incorporated in the various Psy- -PMA samples and tablets were prepared to study the in vitro drug release in acidic (pH= 4), neutral (pH= 7), and basic (pH= 9) media. In the acidic medium, the swelling was more than 1300%. In addition, the biodegradable Psy- -PMA had the highest drug release in the acidic medium. This may be attributed to Fickian diffusion since the drug and the medium in which it was released have the same acidic nature.

关键词： psyllium acetyl salicylic acid in-vitro drug release swelling biodegradation

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Protein microspheres for pulmonary drug delivery

Yongda SUN,

《化学科学与工程前沿（英文）》 2010年第4卷第1期页码 82-86 doi: 10.1007/s11705-009-0307-1

摘要： A new supercritical fluid (SCF) technique was developed for the preparation of microspheres for pulmonary drug delivery (PDD). This technique, based on the anti-solvent process, has incorporated advanced engineering design features to enable improved control of the particle formation process. Human recombinant insulin (HRI) was used as a model compound to evaluate the efficiency of this SCF process. An aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water, leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.

关键词： advanced engineering improved pressure aqueous technique

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Semi-solid materials for controlled release drug formulation: current status and future prospects

Michelle TRAN,Chun WANG

《化学科学与工程前沿（英文）》 2014年第8卷第2期页码 225-232 doi: 10.1007/s11705-014-1429-7

摘要： Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semi-solid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.

关键词： controlled release drug delivery semi-solids polymer excipient

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Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

Xiaojing ZHANG, Weixin ZHANG, Zeheng YANG, Zhao ZHANG

《化学科学与工程前沿（英文）》 2012年第6卷第3期页码 246-252 doi: 10.1007/s11705-012-1299-9

摘要： A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite (HA) hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy (TEM) and field-emission scanning electron microscopy (FESEM) images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 μm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen (IBU) was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

关键词： hydroxyapatite hollow spheres synthesis drug release

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Prevalence of antifolate drug resistance markers in in China

《医学前沿（英文）》 2022年第16卷第1期页码 83-92 doi: 10.1007/s11684-021-0894-x

摘要： The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax and antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009–2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

关键词： drug resistance antifolates molecular markers Plasmodium vivax China

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Clinical analysis of 275 cases of acute drug-induced liver disease

LI Lei, JIANG Wei, WANG Jiyao

《医学前沿（英文）》 2007年第1卷第1期页码 58-61 doi: 10.1007/s11684-007-0012-8

摘要： In order to analyze the causative drugs, clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease, from January 2000 to December 2005, 275 cases diagnosed as acute drug-induced liver diseases according to Maria Criterion and hospitalized in Zhongshan Hospital of Fudan University were retrospectively reviewed. Each was determined by drug history, clinical symptoms and signs, laboratory tests and therapeutic effects. In 41 cases, the diagnosis was confirmed by liver biopsy. The proportion of acute drug-induced liver disease among all of the acute liver injuries was annually increased. The most common drugs which induced acute liver injuries were traditional Chinese herb medicine (23.3%, 64/275 cases), antineoplastics (15.3%, 42/275), hormones and other immunosuppressant agents (13.8%, 38/275), antihypertensive drugs and other cardiovascular drugs (10.2%, 28/275), NSAIDs (8.7%, 24/275) respectively. Hepatocellular injury was the predominant type in these cases (132 cases, 48%). The principal clinical manifestation included nausea (54.8%), fatigue (50.2%), jaundice (35.6%). 27.9% patients were asymptomatic. Most patients were cured with good prognosis. The total effective rate was 94.2% after treatment. The clinicians should pay attention to the prevention, diagnosis and therapy of drug-induced liver disease.

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Introduction to the special issue of the 2009 International Symposium on Crystal Engineering & Drug Delivery

Zhijian CHEN, Wei LI,

《化学科学与工程前沿（英文）》 2010年第4卷第1期页码 1-1 doi: 10.1007/s11705-009-0306-2

摘要：

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Bioorthogonal chemistry based on-demand drug delivery system in cancer therapy

《化学科学与工程前沿（英文）》 2023年第17卷第4期页码 483-489 doi: 10.1007/s11705-022-2227-2

摘要： Benefiting from the advantage of taking place in biological environments without interfering with an innate biochemical process, the bioorthogonal reaction that commonly contains the “bond formation” and “bond cleavage” system has been widely used in targeted therapy for a variety of tumors. Herein, several prominent cases based on the bioorthogonal reaction that tailoring the metabolic glycoengineering tactics to modified cells for cancer immunotherapy, and the innovative tactics for reducing the metal ions’ toxic and side effects with microneedle patches will be highlighted. Based on these applications, the complexities, potential pitfalls, and opportunities of bioorthogonal chemistry in future cancer therapy will be evaluated.

关键词： bioorthogonal reaction cancer therapy metabolic glycoengineering bioorthogonal catalytic patch

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Engineering platelet-mimicking drug delivery vehicles

Quanyin Hu, Hunter N. Bomba, Zhen Gu

《化学科学与工程前沿（英文）》 2017年第11卷第4期页码 624-632 doi: 10.1007/s11705-017-1614-6

摘要： Platelets dynamically participate in various physiological processes, including wound repair, bacterial clearance, immune response, and tumor metastasis. Recreating the specific biological features of platelets by mimicking the structure of the platelet or translocating the platelet membrane to synthetic particles holds great promise in disease treatment. This review highlights recent advancements made in the platelet-mimicking strategies. The future opportunities and translational challenges are also discussed.

关键词： drug delivery platelets nanomedicine bio-inspired biomimetic

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Detection of AmpC β-lactamase and drug resistance of

Rong WANG, Shangwei WU, Xue LI, Ping HE, Yunde LIU

《医学前沿（英文）》 2009年第3卷第1期页码 72-75 doi: 10.1007/s11684-009-0004-y

摘要： In order to provide useful information for effective control and clinical therapy of infection, the resistance status and the rate of carryingAmpC β-lactamase of ( ) were investigated. By VITEK (Bacterial automatic biochemical analyzer), the isolates of were identified and the drug resistance was measured. The AmpC enzyme was detected by the five-disk diffusion test.Antibiotic sensitivity test showed that the resistance effects of to cefazolin, cefoxitin and ampicillin were more serious, with resistant rates of 80.5%, 75.3% and 70.1%, respectively. However, it was more sensitive to Sulperazone (cefoperazone/sulbactam, 13.0%), amikacin (16.9%) and ciprofloxacin (19.5%). Meanwhile, the phenotype detection showed that 35.06% (27/77) isolates of produced AmpC β-lactamase. Most of are multi-drug resistant strains. Sulperazone (cefoperazone/sulbactam), a kind of component β-lactamase, is a more effective antibiotic for treating infection caused by . Unreasonable application of the third generation cephalosporins plays an important role in leading to emergence of high-yield AmpC β-lactamase strains, so antibiotics should be used wisely.

关键词： Enterobacter cloacae AmpC β-lactamase drug resistance

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Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

《医学前沿（英文）》 2012年第6卷第4期页码 376-380 doi: 10.1007/s11684-012-0228-0

摘要：

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

关键词： FOXO3a FOXM1 transcription factor cancer drug resistance tumorigenesis