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Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2798-2818页

作者： Peng Liu Caifang Gao Hongguo Chen Chi Teng Vong Xu Wu Xudong Tang shengpeng wang Yitao wang State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhou 646000China Department of Gastroenterology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China

Inflammatory bowel disease(IBD)is a chronic intestinal disease with painful clinical manifestations and high risks of *** no curative therapy for IBD at present,the development of effective therapeutics is highly *** delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention(EPR)effect caused by the ***,the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug *** researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs,ligandmodified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative *** review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ***,challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

关键词： Receptor-mediated target Inflammatory bowel disease Crohn’s disease Ulcerative colitis Drug delivery Cell adhesion molecule Active target Targeted therapy

A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3367-3382页

作者： Zhejie Chen Wei Hao Caifang Gao Yangyang Zhou Chen Zhang Jinming Zhang Ruibing wang Yitao wang shengpeng wang State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Macao Centre for Research and Development in Chinese Medicine University of MacaoMacao 999078China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China

With the development of synthesis technology, modified messenger RNA(mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 ***-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

关键词： Polyphenol mRNA IL-10 Colitis Inflammatory bowel disease Drug delivery mRNA delivery Supramolecular binding

Rapid Simultaneous Determination of Four Ganoderic Acids in Ganoderma(Chinese Name:Lingzhi)by Direct Infusion-Multiple Reaction Monitoring Cubed

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Journal of Analysis and Testing 2024年第1期8卷 52-62页

作者： Nian Wu Bo Peng Ting Li Pengfei Tu shengpeng wang Bo Li Wenjing Liu Yuelin Song Modern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Amway(China)Botanical Research Center Wuxi 214011China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipa 999078China Amway(Shanghai)Innovation&Science Co. LtdShanghai 201508China School of Pharmacy Henan University of Chinese MedicineZhengzhou 450046China

Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing ***,it is urgent to pursue more efficient approaches for the quality *** of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC *** current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was *** validation assays demonstrated the method to be sensitive,precise,accurate,and *** quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in *** differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and ***,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted *** importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.

关键词： Direct infusion Multiple reaction monitoring cubed High-throughput quantitative analysis Ganoderic acids Ganoderma

Rabdosia serra alleviates dextran sulfate sodium salt-induced colitis in mice through anti-inflammation,regulating Th17/Treg balance,maintaining intestinal barrier integrity,and modulating gut microbiota

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Journal of Pharmaceutical Analysis 2022年第6期12卷 824-838页

作者： Hongyi Li Yi wang Shumin Shao Hui Yu Deqin wang Chuyuan Li Qin Yuan Wen Liu Jiliang Cao Xiaojuan wang Haibiao Guo Xu Wu shengpeng wang State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co. Ltd.Guangzhou510000China College of Pharmacy Shenzhen Technology UniversityShenzhenGuangdong518118China School of Pharmacy Lanzhou UniversityLanzhou730000China Macao Centre for Research and Development in Chinese Medicine University of MacaoMacao999078China

Rabdosia serra(***),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and ***,the chemical composition of *** and its effect against colitis remain *** this study,the chemical composition of the water extract of *** was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of ***,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory factors,and restoring the balance of T helper 17/T regulatory *** also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic *** addition,*** modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-001),and decreasing the abundance of pathogenic bacteria(Turicibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that *** alleviated colitis in a microbiota-dependent ***,our findings provide chemical and biological evidence for the potential application of *** in the management of colitis.

关键词： Rabdosia serra Chemical profile Colitis Inflammation Gut microbiota

Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease

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Research 2021年第1期2021卷 1046-1058页

作者： Yun Tan Yao Liu Yujing Liu Rui Ma Jingshan Luo Huijie Hong Xiaojia Chen shengpeng wang Chuntai Liu Yi Zhang Tongkai Chen Hunan Provincial Key Laboratory of Micro&Nano Materials Interface Science College of Chemistry and Chemical EngineeringCentral South UniversityChangsha 410083China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Key Laboratory of Materials Processing and Mold Ministry of EducationZhengzhou UniversityZhengzhou 450002China

Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson’s disease(PD),presenting within the form of excessive reactive oxygen species(ROS)generation as well as energy *** this dysfunction within brain tissues is an effective approach to treat PD,while unluckily,the blood-brain barrier(BBB)substantially impedes intracerebral drug *** an effort to improve the delivery of efficacious therapeutic drugs to the brain,a drug delivery platform hydrogel(MAG-NCs@Gel)was designed by complexing magnolol(MAG)-nanocrystals(MAG-NCs)into the noninvasive thermosensitive poly(Nisopropylacrylamide)(PNIPAM)with *** as-prepared MAG-NCs@Gel exhibited obvious improvements in drug solubility,the duration of residence with the nasal cavity,and the efficiency of brain targeting,*** all,continuous intranasal MAG-NCs@Gel delivery enabled MAG to cross the BBB and enter dopaminergic neurons,thereby effectively alleviating the symptoms of MPTP-induced *** advantage of the lower critical solution temperature(LCST)behavior of this delivery platform increases its viscoelasticity in nasal cavity,thus improving the efficiency of MAG-NCs transit across the *** such,MAG-NCs@Gel represented an effective delivery platform capable of normalizing ROS and adenosine triphosphate(ATP)in the mitochondria of dopaminergic neurons,consequently reversing the mitochondrial dysfunction and enhancing the behavioral skills of PD mice without adversely affecting normal tissues.

关键词： nasal drugs Rational

Exceptionally flame-retardant flexible polyurethane foam composites:synergistic effect of the silicone resin/graphene oxide coating

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Frontiers of Chemical Science and Engineering 2021年第4期15卷 969-983页

作者： Qian Wu Jincheng Zhang shengpeng wang Bajin Chen Yijun Feng Yongbing Pei Yue Yan Longcheng Tang Huayu Qiu Lianbin Wu Key Laboratory of Organosilicon Chemistry and Materials Technology of Ministry of Education Hangzhou Normal UniversityHangzhou 311121China Collaborative Innovation Center of Zhejiang Province for Manufacturing of Fluorine Silicon Fine Chemicals and Materials Hangzhou Normal UniversityHangzhou 311121China Transfar Zhilian Co. Ltd.Hangzhou 311215China

A facile strategy was developed to fabricate flexible polyurethane(PU)foam composites with exceptional flame *** approach involves the incorporation of graphene oxide(GO)into a silicone resin(SiR)solution,which is then deposited onto a PU foam surface via the dip-coating technique and ***-transform infrared spectroscopy,scanning electron microscopy,and Raman spectroscopy measurements demonstrated that the SiR and GO were successfully coated onto the PU skeleton and the intrinsic porous structure of the PU foam remained *** effects of SiR and GO on the mechanical and thermal stability and flame retardancy of PU composites were evaluated through compression tests,thermogravimetric analysis,vertical combustion tests,and the limiting oxygen *** measurement results revealed that the composites(PU@SiR-GO)showed superior flame retardancy and thermal and mechanical stability compared to pristine PU or PU coated with SiR *** mechanical and thermal stability and the flame-retardant properties of the PU composites were enhanced significantly with increasing GO *** on the composition,microstructure,and surface morphology of PU@SiR-GO composites before and after combustion tests,a possible flame-retardance mechanism is *** work provides a simple and effective strategy for fabricating flame retardant composites with improved mechanical performance.

关键词： flame retardancy flexible polyurethane foam graphene oxide silicone resin

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases

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Journal of Pharmaceutical Analysis 2023年第6期13卷 545-562页

作者： Jiuping Zeng Mingxing Li Qianyun Zhao Meijuan Chen Long Zhao Shulin Wei Huan Yang Yueshui Zhao Anqi wang Jing Shen Fukuan Du Yu Chen Shuai Deng Fang wang Zhuo Zhang Zhi Li Tiangang wang shengpeng wang Zhangang Xiao Xu Wu Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Cell Therapy&Cell Drugs of Luzhou Key Laboratory LuzhouSichuan646000China South Sichuan Institute of Translational Medicine LuzhouSichuan646000China Department of Spleen and Stomach Diseases The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouSichuan646000China School of Medicine Chengdu UniversityChengdu610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan646000China

As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune *** emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 *** RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding *** of small-molecule inhibitors have entered clinical ***,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was ***,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical *** limitations of current development in this area were also discussed to facilitate future research.

关键词： T helper 17 RORγt Small-molecule inhibitor Inflammatory disease Autoimmune disease

Paclitaxel and Cryptotanshinone Loaded Temporal-controlled Nanoparticles for Combinatorial Cancer Therapy

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Paclitaxel and Cryptotanshinone Loaded Temporal-controlled N...

Conditional reprogramming:next generation cell culture

第十四届全国中药和天然药物学术研讨会

作者： shengpeng wang Meiwan Chen Yitao wang University of Macau

Combination therapy has emerged as a promising strategy for treating multidrug resistant（MDR） *** the previous studies,we found that cryptotanshinone（CPT）,an active compound from Salvia miltiorrhiza（Danshen）,can reverse paclitaxel（PTX）-resistant ovarian cancer cells through regulating multiple MDR *** ensure CPT and PTX could be synchronously delivered to cancer cells at the optimum ratio,and CPT could be released faster and earlier than PTX to inactivate P-glycoprotein（P-gp） and inhibit apoptosis barriers,a temporal-controlled nanoparticle system with high drug loading and precise drug ratio was designed and *** core-shell nanoparticles were accomplished through a double self-assembly procedure:the hydrophobic polymeric core containing PTX was obtained by interfacial deposition;then the preformed core was coated with a phospholipid bilayer shell to entrap *** co-delivery nanoparticles enabled a temporal release profile for CPT and PTX:CPT in the outer phase was released faster to inhibit the expression of P-gp and restore apoptotic pathways,while PTX in the core was released in a sustained and slower manner and highly accumulated in drug resistant ovarian cancer cells to further exert therapeutic *** smart co-delivery system was very effective in enhancing the cytotoxicity by increasing the intracellular accumulation of PTX and promoting cell *** a word,such smart co-delivery system has significant promise for an integrative therapy of resistant ovarian cancer.

关键词： Combination therapy multidrug resistance temporal nanoparticles paclitaxel cryptotanshinone

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1360-1381页

作者： Xiaoxiao Wu shengpeng wang Mingxing Li Jing Li Jing Shen Yueshui Zhao Jun Pang Qinglian Wen Meijuan Chen Bin Wei Parham Jabbarzadeh Kaboli Fukuan Du Qijie Zhao Chi Hin Cho Yitao wang Zhangang Xiao Xu Wu Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhou 646000China South Sichuan Institute of Translational Medicine Luzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Department of Oncology and Hematology Hospital(T.C.M)Affiliated to Southwest Medical UniversityLuzhou 646000China Center of Radiation Oncology Hospital(T.C.M)Affiliated to Southwest Medical UniversityLuzhou 646000China Department of Oncology the Affiliated Hospital of Southwest Medical UniversitySouthwest Medical UniversityLuzhou 646000China College of Pharmaceutical Science&Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals Zhejiang University of TechnologyHangzhou 310014China School of Biomedical Sciences Faculty of Medicinethe Chinese University of Hong KongHong KongChina

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming(CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR cocultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase(ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

关键词： culture epithelium programming