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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo Wang Tian Liu Yuetong Huang Chaoying Du Danping Wang Xiyan Wang Qingzhi Lv Zhonggui He Yinglei Zhai Bingjun Sun Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China school of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China school of pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly *** the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug *** study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’*** extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative *** use of C_(20) can balance efficacy and *** results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

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Asian Journal of pharmaceutical Sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China school of Life Science and Biopharmaceutics shenyang pharmaceutical university shenyang 110016 China Department of Basic pharmaceutical Sciences school of pharmacy Husson university Bangor ME 04401USA College of pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies

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Asian Journal of pharmaceutical Sciences 2024年第3期19卷 177-189页

作者： Zhining Ma Yuequan Wang Huiyang He Tong Liu Qikun Jiang Xiaohong Hou school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Liaoning Provincial Institute of Drug Inspection and Testing Shenyang 110036China school of pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory ***,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory ***,the limited corneal permeability of FB significantly restricts its *** this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-***,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer *** the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.

关键词： Flurbiprofen Anti-inflammatory Ophthalmic delivery Chiral resolution Ion-pairing

Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

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Nano Research 2024年第7期17卷 5491-5500页

作者： Yuanhao Yu Shiyi Zuo Jiaxuan Song Lingxiao Li Tian Liu Jiayu Guo Yaqiao Li Danping Wang Qi Lu Helin Wang Dun Zhou Zhonggui He Xiaohong Liu Bingjun Sun Jin Sun school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China

Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting *** present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical *** poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with *** this study,we developed prodrugs by conjugating fatty acids of varying lengths with *** aim was to investigate the balance between efficacy and safety through the selection of appropriate *** synthesized five pH-sensitive doxorubicin-fatty acid *** to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 ***,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor ***,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor *** research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.

关键词： fatty acid prodrug albumin doxorubicin pH-sensitive bond nanomedicines

Long-term efficacy and safety of Huangqi(Radix Astragali Mongolici)-based Traditional Chinese Medicine in diabetic peripheral neuropathy:a Meta-analysis of randomized controlled trials

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Journal of Traditional Chinese Medicine 2024年第2期44卷 229-242页

作者： PING Jing HAO Hongzheng WU Zhenqi ZOU Meijuan LI Zuojing CHENG Gang school of Life Sciences and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110000China Department of Endocrinology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China Department of Research Administration Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110000China

OBJECTIVE:To assess the long-term effectiveness of Huangqi(Radix Astragali Mongolici,HQ)-based Traditional Chinese Medicine(TCM)in the treatment of diabetic peripheral neuropathy(DPN).METHODS:Nine databases were searched to retrieve available randomized controlled trials that compared HQbased TCM and Western Medicines in the treatment of *** methodological quality of the included studies was assessed using the Cochrane bias risk tool,and RevMan 5.4 was used for data *** effect estimates of interest were risk ratio(RR),mean difference(MD)or standardized mean difference(SMD)with 95%confidence interval(CI).RESULTS:The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM[RR=1.30,95%CI(1.21,1.40),P<0.00001]or HQ-based TCM combined with Western Medicines[RR=1.25,95%CI(1.19,1.31),P<0.00001]exhibited higher total efficacy rates than individuals who received Western Medicine *** results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores[MD=-1.50,95%CI(-1.83,-1.17),P<0.00001],and reduced serum interleukin 6[SMD=-0.57,95%CI(-0.87,-0.27),P=0.0002]and tumor necrosis factors-αlevels[SMD=-0.60,95%CI(-0.95,-0.25),P=0.0009].In addition,both HQ-based TCM and HQbased TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine *** terms of blood lipids,oxidative stress and adverse drug reactions,there were no significant differences between the HQ-based TCM groups and the Western Medicine control ***:The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN,although further well-designed RCTs are required to validate these findings.

关键词： Huangqi(Radix Astragali Mongolici) medicine Chinese traditional diabetic peripheral neuropathy Meta-analysis

Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency Department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery ***,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous *** rational design of camptothecins-based prodrug nanoassemblies remains a ***,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug ***,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical *** length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and ***,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and *** findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

Author correction to“Immune-awakening Saccharomyces-inspired nanocarrier for oral target delivery to lymph and tumors”[Acta Pharmaceutica Sinica B 12(2022)4501-4518]

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1478-1482页

作者： Yuling Mao Xiudan Wang Caishun Chen Qinfu Zhao Yanfeng Liu Jinghai Zhang Siling Wang Department of Pharmaceutics School of PharmacyShenyang Pharmaceutical University103 Wenhua RoadShenyang110016China Department of Biomedical Engineering School of Medical DevicesShenyang Pharmaceutical University103 Wenhua RoadShenyang110016China school of Life Science and Bio-pharmaceutics Shenyang Pharmaceutical University103 Wenhua RoadShenyang110016China

The authors regret that there is an error in the article Fig.9D1 due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading,and also a mislabled error in the supp... 详细信息

关键词： correction supporting proof

Glucocorticoids-based prodrug design:Current strategies and research progress

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Asian Journal of pharmaceutical Sciences 2024年第3期19卷 41-78页

作者： Hongbing Liu Muse Ji Peifu Xiao Jingxin Gou Tian Yin Haibing He Xing Tang Yu Zhang Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China school of Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and ***,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and *** notorious side effects seriously compromise patients'quality of life,especially in patients with chronic ***,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive *** them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising *** this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so ***,we also raise issues that need to be focused on during the development of glucocorticoid-based *** review is expected to be helpful for the research and development of novel GCs and prodrugs.

关键词： Glucocorticoids Prodrug design Targeted drug delivery Research progress

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

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Asian Journal of pharmaceutical Sciences 2024年第2期19卷 153-169页

作者： Cong Li Lihong Wang Kexin Zhang Zeyu Wang Zhihang Li Zehao Li Lijiang Chen school of pharmaceutical Science Liaoning UniversityShenyang 110036China

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

关键词： Postoperative tumor treatment Immunotherapy Scaffold-based cancer vaccine Inflammatory neutrophils Sialic acid-modied liposome

β-Carboline alkaloids from the roots of Peganum harmala L.

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Chinese Journal of Natural Medicines 2024年第2期22卷 171-177页

作者： LI Shengge ZHANG Qin WANG Yuetong LIN Bin LI Dahong HUA Huiming HU Xu Henan Key Laboratory of Zhang Zhongjing Formulate and Herbs for Immunoregulation Zhang Zhongjing Traditional School of Chinese MedicineNanyang Institute of TechnologyNanyang 473004China Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China school of pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala *** these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial *** 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-*** structures of these compounds were elucidated by spectroscopic data and quantum mechanical *** biosynthetic pathways of 1−3 were ***,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was ***,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),***,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

关键词： β-Carboline alkaloids Peganum harmala Structure elucidation Cytotoxic activity