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Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

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Asian Journal of Pharmaceutical Sciences 2020年第3期15卷 347-355页

作者： Ni Dong Chune Zhu Junhuang Jiang Di Huang Xing Li Guilan Quan Yang Liu Wen Tan Xin Pan chuanbin wu School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Institute of Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006China Shenyang Pharmaceutical University Benxi 117004China College of Pharmacy Chongqing Medical and Pharmaceutical CollegeChongqing 401331China

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable *** pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

关键词： Microspheres PLGA Peptides Lipid nanoparticles Sustained drug release

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A triple-enhanced chemodynamic approach based on glucosepowered hybrid nanoreactors for effective bacteria killing

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Nano Research 2023年第2期16卷 2682-2694页

作者： Jintao Fu Yixian Zhou Ting Liu Wenhao Wang Yiting Zhao Ying Sun Yiming Zhang Wenxuan Qin Zhongwei Chen Chao Lu Guilan Quan chuanbin wu Xin Pan School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China College of Pharmacy Jinan UniversityGuangzhou 511443China

Rapid evolution of multidrug resistance in bacterial pathogens is outpacing the development of new antibiotics,and chemodynamic therapy(CDT)provides an excellent ***,achieving highly efficient CDT is still a great challenge,since the pH in the infection site is close to neutral and the supply of H_(2)O_(2)is *** herein constructed the antibacterial *** green(ICG)and glucose oxidase(GOx)were incorporated into homologous zeolitic imidazolate framework-8(ZIF-8)nanoparticles coating with metal polyphenol network(MPN)composed by Fe^(3+)and tannic acid(TA).The well-designed nanoreactors could simultaneously break the pH and H_(2)O_(2)limitations,and generate hyperthermia under irradiation,thus realizing a triple-enhanced CDT for high-efficiency ***,the nanoreactors could combine CDT with photothermal therapy(PTT)and photodynamic therapy(PDT),which not only improved the bactericidal efficiency and broadened the antibacterial spectrum,but also alleviated the antibiotics resistance ***,the proposed nanoreactors achieved a robust in vitro bacterial killing against Gram-positive methicillin-resistant Staphylococcus aureus(MRSA)and Gram-negative Pseudomonas *** nanoreactors achieved an 99.7%MRSA reduction in an MRSA-induced murine abscess model accompanied with negligible ***,this study provides a promising strategy for multiple-enhanced CDT and multimodal combined therapy for pathogenic infections.

关键词： metal-organic frameworks glucose oxidase photothermal therapy photodynamic therapy localized bacterial infection

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Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal,intragastric and intravenous administration

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Acta Pharmaceutica Sinica B 2014年第1期4卷 74-78页

作者： Dongmei Meng Haoyang Lu Shanshan Huang Minyan Wei Pingtian Ding Xianglin Xiao Yuehong Xu chuanbin wu School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China The First Affiliated Hospital of Guangzhou Medical College Guangzhou 510120China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang110016China

The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),intragastric(i.g.)and intravenous(i.v.)*** i.n.,*** *** of a single-dose at 10 mg/kg,cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed *** concentration of TMPP in the samples was analyzed by *** area under the concentration-time curve(AUC)and the ratio of the AUCbrain to the AUCplasma(drug targeting efficiency,DTE)was calculated to evaluate the brain targeting efficiency of the drug via these different routes of *** ***,TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex(t_(max)=15 min).The ratio of the AUCbrain dialysates value between *** and *** was 0.68,which was greater than that obtained after ***(0.43).The systemic bioavailability obtained with *** was greater than that obtained by the ***(86.33%vs.50.39%),whereas the DTE of the nasal route was 78.89%,close to that of oral administration(85.69%).These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation,and then crosses the blood-brain barrier(BBB)to reach the cerebral *** administration of TMPP could be a promising alternative to intravenous and oral approaches.

关键词： Tetramethylpyrazine phosphate Intranasal delivery Pharmacokinetics Microdialysis Rat

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Synthesis of taurine-fluorescein conjugate and evaluation of its retina-targeted efficiency in vitro

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Acta Pharmaceutica Sinica B 2014年第6期4卷 447-453页

作者： Meihong Huang Jiaqi Song Bingzheng Lu Huizhi Huang Yizhen Chen Wei Yin Wenbo Zhu Xinwen Su chuanbin wu Haiyan Hu Laboratory of Pharmaceutics School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Pharmacy Department of Guangxi Minzu Hospital Nanning 530001China Department of Pharmacology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F-Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F-Tau. The cellular uptake of F-Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F-Tau compared with fluorescein. As compared with fluorescein, F-Tau showed little toxicity, and was retained longer by cells in uptake experiments. F-Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (Po0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.

关键词： Taurine Taurine-fluorescein con-jugate Retina-targeting ARPE-19 hRMECs Transepithelial permeability

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Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2609-2644页

作者： Liming Lin Jiaying Chi Yilang Yan Rui Luo Xiaoqian Feng Yuwei Zheng Dongyi Xian Xin Li Guilan Quan Daojun Liu chuanbin wu Chao Lu Xin Pan School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China College of Pharmacy Jinan UniversityGuangzhou 511443China Shantou University Medical College Shantou 515041China The Third Affiliated Hospital Sun Yat-sen UniversityGuangzhou 510630China

Membrane-disruptive peptides/peptidomimetics(MDPs)are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes,in contrast to conventional chemotherapeutic drugs,which act on precise targets such as DNA or specific *** to their rapid action,broad-spectrum activity,and mechanisms of action that potentially hinder the development of resistance,MDPs have been increasingly considered as future therapeutics in the drug-resistant ***,growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other *** this review,we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs,and summarize the current development and mechanisms of MDPs alone or in combination with other ***,this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs,minimize side effects,and promote the codelivery of multiple chemotherapeutics,for more efficient antimicrobial and anticancer therapy.

关键词： Membrane-disruptive peptides/peptidomimetics Drug-resistance Drug delivery systems Combination therapy

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Virus-inspired surface-nanoengineered antimicrobial liposome:A potential system to simultaneously achieve high activity and selectivity

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Bioactive Materials 2021年第10期6卷 3207-3217页

作者： Yin Shi Xiaoqian Feng Liming Lin Jing Wang Jiaying Chi Biyuan wu Guilin Zhou Feiyuan Yu Qian Xu Daojun Liu Guilan Quan Chao Lu Xin Pan Jianfeng Cai chuanbin wu College of Pharmacy Jinan UniversityGuangzhouGuangdong511443China Department of Pharmaceutics School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhouGuangdong510006China Medical College Shantou UniversityShantouGuangdong15041China Department of Chemistry University of South FloridaTampaFL33620United States

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and *** simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches,we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side ***,a surface-nanoengineered antimicrobial liposome(SNAL)is developed with the morphological features of enveloped viruses,including a moderate size range,lipid-based membrane structure,and highly lipopeptide-enriched bilayer *** SNAL possesses virus-like infection to bacterial cells,which can mediate high-efficiency and high-selectivity bacteria binding,rapidly attack and invade bacteria via plasma membrane fusion pathway,and induce a local“burst”release of lipopeptide to produce irreversible damage of cell ***,viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations(1.6-6.3μg mL􀀀1),high bactericidal efficiency of>99%within 2 h,>10-fold enhanced selectivity over free lipopeptide,99.8%reduction in skin MRSA load after a single treatment,and negligible *** bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

关键词： Virus-inspired mimics Antimicrobial lipopeptides Liposomes Virus-like infections Activity and selectivity

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Optimization of a doxycycline hydroxypropyl-β-cyclodextrin inclusion complex based on computational modeling

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Acta Pharmaceutica Sinica B 2013年第2期3卷 130-139页

作者： Zhouhua Wang Zixin He Lei Zhang Haohao Zhang Meimei Zhang Xinguo Wen Guilan Quan Xintian Huang Xin Pan chuanbin wu School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Research and Development Center of Pharmaceutical Engineering Sun Yat-sen UniversityGuangzhou 510006China Zhong Yi Pharmaceutical Company Ltd. Guangzhou 510530China School of Mathematics&Computational Sciences Sun Yat-sen UniversityGuangzhou 510275China

To prepare a stable complex of doxycycline(Doxy)and hydroxypropy-β-cyclodextrin(HP-β-CD)for ophthalmic delivery,the optimum formulation and preparation conditions were investigated using response surface methodology(RSM),artificial neural network(ANN)and support vector machine(SVM)*** molar ratios of HP-β-CD/Doxy and Mg^(2+)/Doxy,inclusion time and temperature were selected as independent variables (X_(1)-X_(4)) and inclusion efficiency and stability of the Doxy-HP-β-CD complex were selected as dependent(response)variables(Y_(1) and Y_(2)).The optimal formulation predicted by genetic algorithm(GA)combined with the models was characterized by microscopy and nuclear magnetic resonance spectrometry,and the stability of Doxy in the complex was *** highest values of Y_(1) and Y_(2) were obtained using an ANN model combined with GA which predicted the values of X_(1)-X_(4) to be 4,10.8,12 h and 25℃,*** modeling and optimization results indicated that a feed-forward back-propagation ANN with one hidden layer and 10 hidden units showed better fitting to both responses compared to the RSM and SVM *** proved to be an efficient tool in multiobjective optimization of a pharmaceutical formulation.

关键词： Doxycycline Hydroxypropy-β-cyclo-dextrin Response surface methodology Artificial neural network Support vector machine Genetic algorithm

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PLGA Porous Microspheres Co-loading Afatinib Solid Lipid Nanoparticles and Paclitaxel for EGFR Mutation Drug Resistant NSCLC

PLGA Porous Microspheres Co-loading Afatinib Solid Lipid Nan...

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2018年第十二届中国药物制剂大会

作者：杨堯 Zhengwei Huang Ying Huang Xin Pan chuanbin wu School of Pharmaceutical Sciences Sun Yat-sen University

＜正＞Non-small-cell lung cancers（NSCLCs）,the most common lung cancers,are reported to specifically respond to the epidermal growth factor receptor（EGFR）tyrosine kinase inhibitor（TKI）.Afatinib（AFT）is the secondgeneration EGFR-TKIs and first line treatment in advanced EGFR-mutated NSCLC ***,treatment of these EGFR-TKIs poses unexpected therapeutic challenges,such as emerging of acquired

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Four-Armed Host Defense Peptidomimetics Augmented Vanadium Carbide MXene-Based Microneedle Array for Combined Membranolytic-Photothermal-Photocatalytic Therapy

Four-Armed Host Defense Peptidomimetics Augmented Vanadium C...

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ASTF2023（第五届）抗菌科学与技术论坛

作者：冼冬意 Xiaoqian Feng Chao Lu chuanbin wu College of Pharmacy Jinan University

To fight against localized multidrug-resistant(MDR) bacterial infections,a vanadiumbased MXene composite nanosheet 4 K10@V2C was constructed using a simple procedure by electrostatically driving a four-armed host defense peptidomimetic 4 K10 for coating vanadium carbide(V2C) *** system integrates membranolytic,photothermal,and photocatalytic abilities,realizing a great potential for efficient photo-excited bacteria-killing of focal infections via a microneedle-assisted *** proposed host-defense peptidomimetic augmenting MXene strategy achieves synergistic membranolytic-photothermal effects against biofilm bacteria by mediating high-selectivity bacteria binding,reducing bacteria heat resistance and increasing MXene-to-bacteria heat transfer ***,it is highlight that the degradation products of V2C exert persistent photocatalytic disinfection and adjuvant effects on bacterial rebound *** the 4 K10@V2C nanosheets demonstrate impressive in vitro antimicrobial activity with a ～99.9996%(5.5 log) reduction of methicillin-resistant Staphylococcus aureus and 100% reduction of Pseudomonas aeruginosa at a low photothermal temperature of 54.1℃,the dissolving microneedle system facilitates the transdermal delivery of the 4 K10@V2C nanosheets to eradicate infections with an efficacy superior to that of commercial Bactroban and with no significant in vivo *** a human ex vivo skin infection models,the 4 K10@V2C nanosheets are highly efficacious in eradicating biofilm-associated infections with>99.98%(3.86 log) reduction in the skin MRS A burden after only 15 min of ***,these results indicate that the antibacterial microneedles based on 4 K10@V2C may be used to effectively treat focal biofilm-associated infections caused by MDR bacteria.

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Rapidly Separating Dissolving Microneedles for suppressing inflammatory responses

Rapidly Separating Dissolving Microneedles for suppressing i...

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2018年第十二届中国药物制剂大会

作者：侯嫒琳 Guilan Quan Beibei Yang Xin Pan chuanbin wu School of Pharmaceutical Sciences Sun Yat-sen University

Objective: Recently, the dissolving microneedle（DMN） has become a promising alternative strategy for suppressing inflammatory responses due to its unique properties, including lower pain and higher transdermal permeation. However, the drug delivery efficiency of traditional dissolving microneedles（TDMNs） was often limited by the incomplete insertion of microneedles into the skin, and the long patch application time might increase the skin irritation. The purpose of this study was to establish a rapidly separating dissolving microneedle（RSDMN） system with a rapidly dissolving and separating part to shorten the application time and improve transdermal delivery efficiency. Methods: RSDMN was prepared by a multi-step casting process, diclofenac sodium（DS） was encapsulated within the pyramidal structures（dextran） of the needles while the separating part（hyaluronic acid and sucrose） allowed it to counteract skin indentation during insertion. The morphology, mechanical strength, separating rate, drug permeation profile, skin recovery and irritation of the obtained RSDMNs were examined. The antiinflammatory effects of RSDMNs were investigated in a carrageenan-induced rat paw edema model by calculating the inhibition rate of carrageenan-induced paw edema thickness and evaluating the expression of pro-inflammatory cytokines. The commercial diclofenac sodium cream, TDMNs without the separating part were selected as references. Results: The obtained MNs exhibited a regular and uniform array as observed by SEM. The penetration and separation results showed that the prepared RSDMNs successfully inserted into the rat dorsal skin, dissolved within 30 s and 2 min in gelatin gel and rat dorsal skin, respectively. The skin microchannel caused by the needle penetration could resealed within 1 day and the RSDMNs could decrease the skin irritation by shortening the patch wearing time. The ex-vivo skin permeation results demonstrated that the embedded tips could permeate 50% of the encaps

关键词： Rapidly separating dissolving microneedles anti-inflammatory effect improved permeation efficiency skin irritation

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