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Acta Pharmaceutica Sinica B 2023年第7期13卷 3106-3120页

作者： Jingwen Dong Chenfei Zhu Ying Huang Quanhao Li Jing Li Zheng Wang Yixin Wang Zhanwei Zhou Minjie Sun nmpa key laboratory for research and evaluation of pharmaceutical preparations and excipients State Key Laboratory of Natural MedicinesDepartment of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China

Fibrosis is one of the key factors that lead to the immune exclusion of solid *** degradation of fiber is a promising strategy,its application was still bottlenecked by the side effects of causing metastasis,resulting in the failure of ***,we developed an antimetastatic polymer(HPA)for the delivery of chemo-drug and antifibrotic siPAI-1 to form the ***-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis,and further promoted the sustained infiltration and activation of T cells for killing tumor ***,metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant *** administration of stroma-alleviated immunotherapy increased the infiltration of CD8+T cells to 52.5%in tumor tissues,inhibiting nearly 90%metastasis by HPA in distant *** nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

关键词： Immune exclusion PAI-1 Fibrosis Deep penetration AMD3100 CXCR4/CXCL12 Metastasis Immunotherapy

Natural polysaccharide-based smart CXCR4-targeted nano-system for magnified liver fibrosis therapy

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Chinese Chemical Letters 2024年第2期35卷 341-346页

作者： Liqiong Sun Xinping Luo Chenxi Zhou Zhanwei Zhou Minjie Sun College of Horticulture Nanjing Agricultural UniversityNanjing 210095China nmpa key laboratory for research and evaluation of pharmaceutical preparations and excipients State Key Laboratory of Natural MedicinesDepartment of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China

Activated hepatic stellate cells(aHSCs),the main source of extracellular matrix deposition,are key targets in liver ***,no effective drug specific to aHSCs has been clinically applied due to poor drug delivery ***,we designed a CXC chemokine receptor 4(CXCR4)-targeted reactive oxygen species(ROS)-responsive platform AMD-Dex-ROS-responsive-sorafenib(ARS)based on natural polysaccharide and thioctic acid frame,which can deliver anti-fibrosis drug represented by sorafenib specifically to aHSCs on account of CXCR4 over-expression on aHSCs,and smartly disassemble via ROS-responsive thioketal rupture relying on high intracellular ROS in HSCs,realized on-demand drug release and effective liver fibrosis ***,in this platform,the CXCR4 antagonist AMD3100 not only enhanced aHSCs targeting efficiency of sorafenib but also effectively magnified the aHSCs elimination of sorafenib by blocking stroma cell derived factor-1(SDF-1)/CXCR4-induced aHSCs protection,resulting in synergistic anti-fibrosis *** platform provided a new approach for drug delivery system design and liver fibrosis treatment.

关键词： Nanoparticle CXCR4 antagonism ROS-responsive Hepatic stellate cells Liver fibrosis

Nanomedicine potentiates mild photothermal therapy for tumor ablation

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Asian Journal of pharmaceutical Sciences 2021年第6期16卷 738-761页

作者： Zijun Jiang Tianyi Li Hao Cheng Feng Zhang Xiaoyu Yang Shihao Wang Jianping Zhou Yang Ding key laboratory of Drug Quality Control and Pharmacovigilance(Ministry of Education) State Key Laboratory of Natural MedicinesNMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and ExcipientsDepartment of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China

The booming photothermal therapy(PTT)has achieved great progress in non-invasive oncotherapy,and paves a novel way for clinical *** note,mild temperature PTT(mPTT)of 42–45°C could avoid treatment bottleneck of the traditional PTT,including nonspecific injury to normal tissues,vasculature and host antitumor ***,cancer cells can resist mPTT via heat shock response and autophagy,thus leading to insufficient mPTT monotherapy to ablate *** overcome the deficient antitumor efficacy caused by thermo-resistance of cancer cells and mono mPTT,synergistic therapies towards cancer cells have been conducted with *** review summarizes the recent advances in nanomedicine-potentiated mPTT for cancer treatment,including strategies for enhanced single-mode mPTT and mPTT plus synergistic ***,challenges and prospects for clinical translation of nanomedicine-potentiated mPTT are discussed.

关键词： Nanomedicine Mild temperature PTT Thermo-resistance Promote mPTT monotherapy Synergistic therapy

Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

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Chinese Chemical Letters 2024年第7期35卷 377-382页

作者： Mengjuan Sun Muye Zhou Yifang Xiao Hailei Tang Jinhua Chen Ruitao Zhang Chunjiayu Li Qi Ya Qian Chen Jiasheng Tu Qiyue Wang Chunmeng Sun nmpa key laboratory for research and evaluation of pharmaceutical preparations and excipients China Pharmaceutical UniversityNanjing 210009China State key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 211198China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Jiangsu Provincial key laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityNanjing 210009China School of pharmaceutical Science Nanjing Tech UniversityNanjing 211816China

Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral *** with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid *** address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this *** micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),*** net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of ***-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral *** indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse ***,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

关键词： Polyion complex micelle Size-switchable Revisable size-change pH response Antiangiogenic cancer

Leveraging nano-engineered mesenchymal stem cells for intramedullary spinal cord tumor treatment

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Chinese Chemical Letters 2023年第5期34卷 449-455页

作者： Lu Tang Mengying Xie Jing Li Yijun Mei Yuqi Cao Qiaqia Xiao Haijuan Dong Yuhui Zhang Wei Wang Department of Pharmaceutics State Key Laboratory of Natural MedicinesSchool of PharmacyChina Pharmaceutical UniversityNanjing 210009China nmpa key laboratory for research and evaluation of pharmaceutical preparations and excipients China Pharmaceutical UniversityNanjing 210009China The Public laboratory Platform China Pharmaceutical UniversityNanjing 210009China Department of Spine Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Intramedullary spinal cord tumor(IMSCT)is comparatively rare malignant tumor in the central nervous system and is very difficult accessible by conventional chemotherapy ***,there are very limited researches for IMSCT treatment using *** fill this gap,we originally reported a targeted strategy by leveraging nano-engineered mesenchymal stem cells(MSCs)for synergistic antiIMSCT *** this study,two mode drugs paclitaxel(PTX)and metformin(MET)were co-loaded in maleimide-modified poly(lactic-co-glycolicacid)(PLGA-MAL)nanoparticles,which were further conjugated onto MSCs surface via the thioether bond formed between PLGA-MAL and MSCs without affecting the migration ability of *** to the excellent tumor tropism and penetrability of MSCs and good biodegradability of PLGA,the designed drug delivery platform could accurately target IMSCT sites to exert long-term synergistic antitumor efficacy,exhibiting promising research value for alternative IMSCT management beyond surgery.

关键词： Mesenchymal stem cell Intramedullary spinal cord tumor Metformin Nanosystem Targeted drug delivery

Multifunctional inorganic nanomaterials for cancer photoimmunotherapy

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Cancer Communications 2022年第2期42卷 141-163页

作者： Lu Tang Aining Zhang Ziyao Zhang Qingqing Zhao Jing Li Yijun Mei Yue Yin Wei Wang State key laboratory of Natural Medicines Department of PharmaceuticsSchool of PharmacyChina Pharmaceutical UniversityNanjingJiangsuP.R.China National Medical Products Administration key laboratory for research and evaluation of pharmaceutical preparations and excipients China Pharmaceutical UniversityNanjingJiangsuP.R.China

Phototherapy and immunotherapy in combination is regarded as the ideal ther-apeutic modality to treat both primary and metastatic ***-apy uses different immunological approaches to stimulate the immune system to identify tumor cells for targeted *** destroys the pri-mary tumors by light irradiation,which induces a series of immune responses through triggering immunogenic cancer cell ***,when integrat-ing immunotherapy with phototherapy,a novel anti-cancer strategy called pho-toimmunotherapy(PIT)is *** synergistic treatment modality can not only enhance the effectiveness of both therapies but also overcome their inherent limitations,opening a new era for the current anti-cancer ***,the advancement of nanomaterials affords a platform for *** all these nanomaterials,inorganic nanomaterials stand out as idealmediators in PIT due to their unique physiochemical *** nanomaterials can not only serve as carriers to transport immunomodulatory agents in immunotherapy owing to their excellent drug-loading capacity but also function as photother-mal agents or photosensitizers in phototherapy because of their great optical *** this review,the recent advances of multifunctional inorganic nanomaterial-mediated drug delivery and their contributions to cancer PIT will be highlighted.

关键词： biodegradability cancer photoimmunotherapy immune stimulation inorganic nanomaterial nanoparticles targeted drug delivery

Structure based release kinetics analysis of doxazosin mesylate sustained-release tablets using micro-computed tomography

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Asian Journal of pharmaceutical Sciences 2024年第6期19卷 154-162页

作者： Qian Liu Mengqing Zan Hanhan Huang Hai Su Wenjing Zhang Lingyun Ma Guangchao Zhang Zunjian Zhang Jiwen Zhang Jianzhao Niu Mingdi Xu nmpa key laboratory for Quality research and evaluation of Chemical Drugs National Institutes for Food and Drug ControlBeijing 100050China China pharmaceutical University Nanjing 210009China nmpa key laboratory for Quality research and evaluation of pharmaceutical excipients National Institutes for Food and Drug ControlBeijing 100050China Center for Drug Delivery System Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage ***,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping *** their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release *** structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic ***,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic ***,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%*** conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.

关键词： Doxazosin mesylate sustained-release tablets Osmotic pump tablets Micro-computed tomography Three-dimensional structures Ethanol

Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

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Nano-Micro Letters 2021年第9期13卷 223-237页

作者： Liping Huang Yiyi Zhang Yanan Li Fanling Meng Hongyu Li Huimin Zhang Jiasheng Tu Chunmeng Sun Liang Luo College of Life Science and Technology National Engineering Research Center for NanomedicineHuazhong University of Science and TechnologyWuhan 430074People’s Republic of China State key laboratory of Natural Medicines NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipientsand Department of PharmaceuticsSchool of PharmacyChina Pharmaceutical University24 Tong Jia XiangNanjing 210009China Hubei key laboratory of Bioinorganic Chemistry and Materia Medica School of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan 430074People’s Republic of China School of Food Science and pharmaceutical Engineering Nanjing Normal UniversityNanjing 210023People’s Republic of China

The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer *** delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising,yet greatly challenging,to reverse postoperative ***,an injectable hierarchical gel matrix,composed of dual lipid gel(DLG)layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios,was developed to achieve the time-programmed sequential delivery of combined cancer *** outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide(GO)*** under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages(TAMs)and promote an immunogenic tumor *** inner layer,loaded with anti-CD47 antibody(aCD47),could maintain the gel state for a much longer time,enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory proteinα(SIRPα)pathway for a long-term antitumor *** vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape,thereby boosting the systemic immune responses.

关键词： Hierarchical hydrogel Sorafenib Postoperative immunosuppression reversal Tumor-associated macrophages Anti-CD47 antibody

Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2006-2025页

作者： Bingwen Ding Zhu Zhu Cong Guo Jiaxin Li Yong Gan Miaorong Yu State key laboratory of Drug research and Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China School of Pharmacy Henan UniversityKaifeng 475004China nmpa key laboratory for Quality research and evaluation of pharmaceutical excipients National Institutes for Food and Drug ControlBeijing 100050China

Diabetes,characterized by hyperglycemia,is a major cause of death and disability ***,such as insulin and glucagon-like peptide-1(GLP-1)analogs,have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the *** to subcutaneous injection,oral administration of anti-diabetic peptides is a preferred ***,biological barriers significantly reduce the efficacy of oral peptide *** advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating *** review will highlight(1)the benefits of oral anti-diabetic peptide therapeutics;(2)the biological barriers for oral peptide delivery,including pH and enzyme degradation,intestinal mucosa barrier,and biodistribution barrier;(3)the delivery platforms to overcome these biological ***,the review will discuss the prospects in this *** information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.

关键词： Oral peptides Diabetes Delivery platforms Insulin Glucagon-like peptide-1 Biodistribution Biological barriers Targeted delivery

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1709-1718页

作者： Kena Zhao Tao Guo Caifen Wang Yong Zhou Ting Xiong Li Wub Xue Li Priyanka Mittal Senlin Shi Ruxandra Gref Jiwen Zhang College of pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 311402China Center for Drug Delivery System Shanghai Institute of Materia MedicaState Key Laboratory of Drug ResearchChinese Academy of SciencesShanghai 201203China nmpa key laboratory for Quality research and evaluation of pharmaceutical excipients National Institutes for Food and Drug ControlBeijing 100050China key laboratory of Modern Chinese Medicine preparations Ministry of EducationJiangxi University of Traditional Chinese MedicineNanchang 330004China Universite´Paris-Saclay CNRS 8214Institut des Sciences Mole´culaires d’OrsayOrsay 91405France University of Chinese Academy of Sciences Beijing 100049China

It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related *** the inhalable micron-sized crystals ofγ-cyclodextrin metal-organic framework(CD-MOF)was utilized as dry powder inhalers(DPIs)carrier with high fine particle fraction(FPF),it was found in this research that the encapsulation of a glycoside compound,namely,scutellarin(SCU)in CD-MOF could significantly enhance its laryngeal ***,SCU loading into CD-MOF was optimized by ***,a series of characterizations were carried out to elucidate the mechanisms of drug ***,the laryngeal deposition rate of CD-MOF was 57.72±2.19%improved by SCU,about two times higher than that of CD-MOF,when it was determined by Next Generation Impactor(NGI)at 65 L/*** a proof of concept,pharyngolaryngitis therapeutic agent dexamethasone(DEX)had improved laryngeal deposition after being co-encapsulated with SCU in *** molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the SCU@CD-MOF,which defined the enhanced laryngeal *** conclusion,the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases.

关键词： Laryngeal delivery g-Cyclodextrin metalorganic framework Scutellarin Dexamethasone Molecular simulation