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| 1 | ROS-responsive drug delivery systems for biomedical applications显示文摘In the field of biomedicine, stimuli-responsive drug delivery systems(DDSs) have become increasingly popular due to their site-specific release ability in response to a certain physiological stimulus, which may result in both enhanced treatment outcome and reduced side effects. Reactive oxygen species(ROS) are the unavoidable consequence of cell oxidative metabolism. ROS play a crucial part in regulating biological and physiological processes,whereas excessive intracellular ROS usually lead to the oxidation stress which has implications in several typical diseases such as cancer, inflammation and atherosclerosis. Therefore,ROS-responsive DDSs have elicited widespread popularity for their promising applications in a series of biomedical research because the payload is only released in targeted cells or tissues that overproduce ROS. According to the design of ROS-responsive DDSs, the main release mechanisms of therapeutic agents can be ascribed to ROS-induced carrier solubility change, ROS-induced carrier cleavage or ROS-induced prodrug linker cleavage. This review summarized the latest development and novel design of ROS-responsive DDSs and discussed their design concepts and the applications in the biomedical field. | Wenhui Tao Zhonggui He | 2018 | Asian Journal of Pharmaceutical Sciences2018，13，2： | 12 |
| 2 | The endocytosis and intracellular fate of nanomedicines: Implication for rational design显示文摘Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines. | Longfa Kou Jin Sun Yinglei Zhai Zhonggui He | 2013 | Asian Journal of Pharmaceutical Sciences2013，8，1： | 10 |
| 3 | Redox-sensitive prodrug nanoassemblies based on linoleic acid-modified docetaxel to resist breast cancers显示文摘Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione(GSH) and reactive oxygen species(ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid(LA) and docetaxel(DTX). This mono thioether-linked conjugates(DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve(AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4 T1 xenograft. It turned out this nanoassemblies couldenhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy. | Meng Li Liwen Zhao Tao Zhang Yue Shu Zhonggui He Yan Ma Dan Liu Yongjun Wang | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 10 |
| 4 | Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy显示文摘Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a 'stealth' state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a 'recognition' state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution. | Lu Zhong Lu Xu Yanying Liu Qingsong Li Dongyang Zhao Zhenbao Li Huicong Zhang Haotian Zhang Qiming Kan Yongjun Wang Jin Sun Zhonggui He | 2019 | Acta Pharmaceutica Sinica B2019，9，2： | 7 |
| 5 | Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs显示文摘The aim of the present study was to investigate virtual population pharmacokinetic using physiologically based pharmacokinetic(PBPK) model for evaluating bioequivalence of oral lacidipine formulations in dogs. The dissolution behaviors of three lacidipine formulations including one commercial product and two self-made amorphous solid dispersions(ASDs)capsules were determined in 0.07% Tween 80 media. A randomized 3-period crossover design in 6 healthy beagle dogs after oral administration of the three formulations at a single dose of 4 mg was conducted. The PBPK modeling was utilized for the virtual bioequivalence study.In vitro dissolution experiment showed that the dissolution behaviors of lacidipine amorphous solid dispersions(ASDs) capsules, which was respectively prepared by HPMC-E5 or Soluplus, as polymer displayed similar curves compared with the reference formulation in 0.07% Tween 80 media. In vivo pharmacokinetics experiments showed that three formulations had comparable maximum plasma drug concentration(Cmax), and the time(Tmax) to reach Cmax of lacidipine tablet, which was prepared by Soluplus, as polymer was slower than other two formulations in consistency with the in vitro dissolution rate. The 90% confidence interval(CI) for the Cmax, AUC0–24 h and AUC0–∞ of the ratio of the test drug to the reference drug exceeded the acceptable bioequivalence(BE) limits(0.80–1.25). However, the 90% CI of the AUC0–24 h, AUC0–∞ and Cmax of the ratio of test to reference drug were within the BE limit,calculated using PBPK modeling when the virtual subjects reached 24 dogs. The results all demonstrated that virtual bioequivalence study can overcome the inequivalence caused by inter-subject variability of the 6 beagle dogs involved in in vivo experiments. | Bin Yang Chunnuan Wu Bin Ji Mingrui Wu Zhonggui He Lei Shang Jin Sun | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，1： | 5 |
| 6 | Emerging role of natural products in cancer immunotherapy显示文摘Cancer immunotherapy has become a new generation of anti-tumor treatment,but its indications still focus on several types of tumors that are sensitive to the immune system.Therefore,effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy.Natural products are reported to have this effect on cancer immunotherapy,including cancer vaccines,immune-check points inhibitors,and adoptive immune-cells therapy.And the mechanism of that is mainly attributed to the remodeling of the tumorimmunosuppressive microenvironment,which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy.Therefore,this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism.And we found that saponins,polysaccharides,and flavonoids are mainly three categories of natural products,which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment.Besides,this review also collected the studies about nano-technology used to improve the disadvantages of natural products.All of these studies showed the great potential of natural products in cancer immunotherapy. | Songtao Dong Xiangnan Guo Fei Han Zhonggui He Yongjun Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 5 |
| 7 | Application of hot melt extrusion to enhance the dissolution and oral bioavailability of oleanolic acid显示文摘The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA. | Nannan Gao Mengran Guo Qiang Fu Zhonggui He | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，1： | 5 |
| 8 | Ratiometric delivery of doxorubicin and berberine by liposome enables superior therapeutic index than Doxil?显示文摘Although the appearance of Doxil alleviated the cardiotoxicity of DOX, the progression-free survival of patients was not prolonged compared with traditional medication regimens, and side effects such as hand-foot syndrome has occurred. In order to solve this dilemma, we have designed a novel co-delivery strategy to construct a co-loaded liposome of berberine(BER) and doxorubicin(DOX), which was called Lipo Be Do. The optimal synergistic ratio of the two drugs was screened by cell cytotoxicity experiments in vitro, and the optimal attenuation ratio was further determined by in vivo cardiac H&E staining pathological sections. The optimal combination treatment caused a robust increase in apoptotic cells of 4T1, as compared to drug alone treatment. The prepared co-loaded liposome, Lipo Be Do, had high encapsulation efficiency and good stability. The nanoliposome carrier controlled the biological fate of the drugs and maintained a pre-defined optimal ratio in vivo. The Lipo Be Do significantly inhibited tumor growth in 4T1 murine mammary carcinoma model compared with Doxil(P < 0.05), and completely overcame the myocardial rupture toxicity caused by Doxil in mice. Our co-loaded liposome delivery platform technology provided a new direction for the clinical treatment of triple-negative breast cancer and the safe application of DOX. | Ruoshi Zhang Yingxi Zhang Yue Zhang Xin Wang Xuanming Gao Yuyan Liu Xuanbo Zhang Zhonggui He Dun Wang Yongjun Wang | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，3： | 4 |
| 9 | Can semipermeable membranes coating materials influence in vivo performance for paliperidone tri-layer ascending release osmotic pump tablet:In vitro evaluation and in vivo pharmacokinetics study显示文摘One purpose of this study was to develop a paliperidone(PAL)tri-layer ascending release pushepull osmotic pump(TA-PPOP)tablet which could meet the needs of clinical applications.And another purpose was to investigate whether different coating materials influenced in vivo performance of TA-PPOP.The ascending release mechanism of this trilayer delivery system on theory was elaborated.TA-PPOP was prepared by means of coating with cellulose acetate(CA)or ethyl cellulose(EC).Several important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated.The optimization of formulation and process was conducted by comparing different in vitro release behaviors of PAL.In vitro dissolution studies indicated that both the two formulations of different coating materials were able to deliver PAL at an ascending release rate during the whole 24 h test.The in vivo pharmacokinetics study showed that both self-made PPOP tablets with different coating had a good in vitro-in vivo correlation(IVIVC)and were bioequivalent with the brand product,which demonstrated no significant influence of the coating materials on the in vivo release acceleration of TA-PPOP. | Guangjing Li Yongjun Wang Hongming Chen Donglei Leng Panqin Ma Yanjie Dong Lifang Gao Zhonggui He | 2015 | Asian Journal of Pharmaceutical Sciences2015，10，2： | 4 |
| 10 | Erythrocyte membrane-camouflaged carrier-free nanoassembly of FRET photosensitizer pairs with high therapeutic efficiency and high security for programmed cancer synergistic phototherapy显示文摘Phototherapy has been intensively investigated as a non-invasive cancer treatment option.However,its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity.To achieve high therapeutic efficiency and high security,a nanoassembly of Forster Resonance Energy Transfer(FRET)photosensitizer pairs is developed on basis of dual-mode photosensitizer co-loading and photocaging strategy.For proof-of-concept,an erythrocyte-camouflaged FRET pair co-assembly of chlorine e6(Ce6,FRET donor)and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide(DiR,FRET acceptor)is investigated for breast cancer treatment.Notably,Ce6 in the nanoassemby is quenched by DiR and could be unlocked for photodynamic therapy(PDT)only when DiR is photobleached by 808-nm laser.As a result,Ce6-caused phototoxicity could be well controlled.Under cascaded laser irradiation(808-660 nm),tumor-localizing temperature rise following laser irradiation on DiR not only induces tumor cell apoptosis but also facilitates the tumor penetration of NPs,relieves tumor hypoxia,and promotes the PDT efficacy of Ce6.Such FRET pair-based nanoassembly provides a new strategy for developing multimodal phototherapy nanomedicines with high efficiency and good security. | Xuanbo Zhang Jianchen Xiong Kaiyuan Wang Han Yu Bingjun Sun Hao Ye Zhiqiang Zhao Ning Wang Yuequan Wang Shenwu Zhang Wutong Zhao Haotian Zhang Zhonggui He Cong Luo Jin Sun | 2021 | Bioactive Materials2021，6，8： | 4 |
| 11 | Intestinal OCTN2-and MCT1-targeted drug delivery to improve oral bioavailability显示文摘Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs,thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery.In particular,intestinal carnitine/organic cation transporter 2(OCTN2)and mono-carboxylate transporter protein 1(MCT1)possess high transport capacities and complementary distributions.Therefore,we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review.First,basic information of the two transporters is reviewed,including their topological structures,characteristics and functions,expression and key features of their substrates.Furthermore,progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed,including improvements in the oral absorption of anti-inflammatory drugs,antiepileptic drugs and anticancer drugs.Finally,the potential of a dual transporter-targeting strategy is discussed. | Gang Wang Lichun Zhao Qikun jiang Yixin Sun Dongyang Zhao Mengchi Sun Zhonggui He Jin sun Yang Wang | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，2： | 3 |
| 12 | Bacteria-Mediated Synergistic Cancer Therapy:Small Microbiome Has a Big Hope显示文摘The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations. | Xinyu Lou Zhichao Chen Zhonggui He Mengchi Sun Jin Sun | 2021 | Nano-Micro Letters2021，13，2： | 3 |
| 13 | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies显示文摘Homodimeric prodrug-based self-assembled nanoparticles,with carrier-free structure and ultrahigh drug loading,is drawing more and more attentions.Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage.The influence of the linkages on the self-assembly,in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research.Herein,three docetaxel(DTX)homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages.Interestingly,compared with the other two linkages,the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs,thus improving the stability,circulation time and tumor targeting of prodrug nanoassemblies.Besides,the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells.Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells,their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells,which finally“turned the table”.Our study illustrates the crucial role of linkages in homodimeric prodrugs,and gives valuable proposal for the development of advanced nano-DDS for cancer treatment. | Lingxiao Li Shiyi Zuo Fudan Dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He | 2021 | Asian Journal of Pharmaceutical Sciences2021，16，3： | 3 |
| 14 | Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy显示文摘Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines. | Shenwu Zhang Yuequan Wang Zhiqiang Kong Xuanbo Zhang Bingjun Sun Han Yu Qin Chen Cong Luo Jin Sun Zhonggui He | 2021 | Acta Pharmaceutica Sinica B2021，11，11： | 3 |
| 15 | Recent advances in bacteriophage-based therapeutics:Insight into the post-antibiotic era显示文摘Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again.As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages(such as bacteriophage phi X174 and Pyo bacteriophage complex liquid) entered into phase Ⅲ clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced(i) the pharmacological mechanisms and advantages of antibacterial bacteriophages,(ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and(iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development. | Hao Ling Xinyu Lou Qiuhua Luo Zhonggui He Mengchi Sun Jin Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，12： | 3 |
| 16 | Co-amorphous solid dispersion systems of lacidipine-spironolactone with improved dissolution rate and enhanced physical stability显示文摘Co-amorphous solid dispersion(C-ASD)systems have attracted great attention to improve the solubility of poorly soluble drugs,but the selection of an appropriate stabilizer to stabilize amorphous forms is still a huge challenge.Herein,C-ASD system of two clinical combined used drugs(lacidipine(LCDP)and spironolactone(SPL))as stabilizers to each other,was prepared by solvent evaporation method.The effects of variation in molar ratio of LCDP and SPL(3:1,1:1,1:3,1:6,and 1:9)on the drug release characteristics were explored.Polarized light microscopy(PLM),powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC)and thermogravimetric analysis(TGA)were employed to evaluate the solid states.Prepared C-ASDs were further studied for their stability under the high humidity(RH 92.5%).Further analysis of C-ASDs via Fourier-transform infrared spectroscopy(FTIR)and Raman spectroscopy confirmed that hydrogen bond interactions between the two drugs played a significant role in maintaining the stability of the C-ASDs systems.Moreover,molecular dynamic(MD)simulations provided a clear insight into the stability mechanism at the molecular level.This study demonstrated the novel drug-drug C-ASDs systems is a promising formulation strategy for improved dissolution rate and enhanced physical stability of poorly soluble drugs. | Zhaomeng Wang Mengchi Sun Tian Liu Zisen Gao Qing Ye Xiao Tan Yanxian Hou Jin Sun Dun Wang Zhonggui He | 2019 | Asian Journal of Pharmaceutical Sciences2019，14，1： | 2 |
| 17 | The effect of cephalexin in influencing the pharmacokinetics of a novel drug–5’-valyl-cytarabine hydrochloride显示文摘The aim of this study is to investigate the pharmacokinetics of 5′-valyl-cytarabine hydrochloride(OPC) when co-administered with cephalexin, which are both the substrates of PepT 1.The drugs were administered orally by gavage. Blood samples were collected from the orbital plexus of the rats after oral administration of drug solutions. A new high-performance liquid chromatographic method was validated and used for determination of the two drugs. Pharmacokinetic parameters were calculated using DAS 2.1.1 software with noncompartmental analysis. After oral administration of OPC and co-administration of OPC and cephalexin,there were significant differences in the main pharmacokinetic parameters. The main pharmacokinetic parameters for the OPC group and the co-administrative group were as follows:AUC0-10(18,168.7 ± 2561.4) ng·h/ml and(13,448.5 ± 2544.73) ng·h/ml, AUC0-∞(18,683.1 ± 3066.5)ng·h/ml and(13,721.1 ± 2683.0) ng·h/ml, Cmax(6654.8 ± 481.3) ng/ml and(4765.1 ± 928.9) ng/ml, respectively. The results showed that the bioavailability of OPC could be reduced when co-administered with cephalexin, suggesting that the efficacy of a novel drug might be reduced when it came to combination use of β-lactam antibiotics. | Xiaotong Song Yinghua Sun Chenyao Zhao Zhonggui He | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，2： | 2 |
| 18 | Emerging systemic delivery strategies of oncolytic viruses:A key step toward cancer immunotherapy显示文摘Oncolytic virotherapy(OVT)is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus(OV)-mediated immunostimulation.Notably,talimogene laherparepvec(T-Vec)developed by the Amgen company in 2015,is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment.However,the systemic administration of OVs still faces huge challenges,including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy.Recently,state-of-the-art progress has been made in the development of systemic delivery of OVs,which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery.Herein,this review describes the general characteristics of OVs,focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT.The emerging multiple systemic administration approaches of OVs are summarized in the past five years.In addition,the combination treatments between OVT and traditional therapies(chemotherapy,thermotherapy,immunotherapy,and radiotherapy,etc.)are highlighted.Last but not least,the future prospects and challenges of OVT are also discussed,with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy. | Weiyue Ban Jianhuan Guan Hanwei Huang Zhonggui He Mengchi Sun Funan Liu Jin Sun | 2022 | Nano Research2022，15，5： | 2 |
| 19 | Development and validation of a UPLC–MS/MS assay for the determination of gemcitabine and its L-carnitine ester derivative in rat plasma and its application in oral pharmacokinetics显示文摘A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats. | Gang Wang Dongyang Zhao Hongxiang Chen Dawei Ding Longfa Kou Lifang Sun Chenxia Hao Xincong Li Kai Jia Qiming Kan Xiaohong Liu Zhonggui He Jin Sun | 2017 | Asian Journal of Pharmaceutical Sciences2017，12，5： | 2 |
| 20 | Naringenin nanocrystals for improving antirheumatoid arthritis activity显示文摘Naringenin(NAR)is recognized for its anti-inflammatory activity.However,the clinical application of NAR is limited by low bioavailability,which is attributed to its poor aqueous solubility.In this study,we aimed to improve the therapeutic efficacy of NAR by formulating it into nanocrystals(NCs)via wet milling.The obtained NARNCs exhibited superior dissolution behaviors,increased cellular uptake,and enhanced transcellular diffusion relative to those of bulk NAR.Oral administration of NARNCs also significantly improved bioavailability in rats.In addition,the NARNCs effectively improved rheumatoid arthritis treatment in collagen-induced arthritic rats by reducing inflammatory cell infiltration and synovial damage.These results indicate that NARNCs provides a promising strategy for rheumatoid arthritis treatment. | Guangshuai Zhang Guangyuan Sun Haishan Guan Mo Li Yanhua Liu Baocheng Tian Zhonggui He Qiang Fu | 2021 | Asian Journal of Pharmaceutical Sciences2021，16，6： | 1 |
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