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A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2404-2416页

作者： Yixian Zhou Boyi Niu Biyuan Wu Sulan Luo Jintao Fu Yiting Zhao Guilan Quan Xin Pan Chuanbin Wu School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China College of Pharmacy Jinan UniversityGuangzhou 510632China

pulmonary drug delivery has attracted increasing attention in biomedicine,and porous particles can effectively enhance the aerosolization performance and bioavailability of ***,the existing methods for preparing porous particles using porogens have several drawbacks,such as the inhomogeneous and uncontrollable pores,drug leakage,and high risk of *** this study,a series of cyclodextrin-based metal-organic framework(CD-MOF)particles containing homogenous nanopores were delicately engineered without *** with commercial inhalation carrier,CDMOF showed excellent aerosolization performance because of the homogenous nanoporous *** great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments,including cytotoxicity assay,hemolysis ratio test,lung function evaluation,in vivo lung injury markers measurement,and histological *** results of ex vivo fluorescence imaging showed the high deposition rate of CD-MOF in ***,all results demonstrated that CD-MOF was a promising carrier for pulmonary drug *** study may throw light on the nanoporous particles for effective pulmonary administration.

关键词： pulmonary drug delivery Metal-organic framework Inhalable dry powder Nanoporous particle

Protein microspheres for pulmonary drug delivery

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Frontiers of Chemical Science and Engineering 2010年第1期4卷 82-86页

作者： Yongda SUN Tianjin Crystec Pharmaceutical Technology Limited Tianjin 300457China

A new supercritical fluid(SCF)technique was developed for the preparation of microspheres for pulmonary drug delivery(PDD).This technique,based on the anti-solvent process,has incorporated advanced engineering design features to enable improved control of the particle formation *** recombinant insulin(HRI)was used as a model compound to evaluate the efficiency of this SCF *** aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water,leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.

关键词： supercritical fluid anti-solvent process pulmonary drug delivery protein microsphere human recombinant insulin

Inhalation Devices and pulmonary drug delivery

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Journal of Clinical and Nursing Research 2022年第3期6卷 54-72页

作者： Sara M Tony Mohamed EA Abdelrahim Beni-Suef Specialized Hospital Beni-Suef Egypt Clinical Pharmacy Department Faculty of PharmacyBeni-Suef University Beni-SuefEgypt

Inhaled drug delivery is mainly used to treat pulmonary airway disorders by transporting the drug directly to its targeted location for *** decreases the dose required to exert a therapeutic effect and minimizes any potential adverse *** drug delivery to air passages facilitates a faster onset of action;it also minimizes irritation to the stomach,which frequently occurs with oral medications,and prevents the exposure of drugs to pre-systemic metabolism that takes place in the intestine and *** addition to that,the lung is regarded as a route for transporting medications throughout the entire body's blood *** type of medication and the device used to deliver it are both important elements in carrying the drug to its target in the *** types of inhalation methods are used in inhaled *** differ in the dose delivered,inhalation technique,and other *** paper will discuss these factors in more detail.

关键词： pulmonary drug delivery pMDI,DPI Nebulizer

Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2565-2584页

作者： Yi Guo Hriday Bera Changzhi Shi Li Zhang Dongmei Cun Mingshi Yang Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2100Denmark

pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma,chronic obstructive pulmonary diseases and respiratory infections,and systemic diseases such as *** inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are *** inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration,but also enhance the clinical benefits to the patients with improved therapeutic *** article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled *** starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure,which is followed by recent advances in various strategies to overcome these ***,the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

关键词： pulmonary drug delivery pulmonary clearance pathways pulmonary exposure Pharmaceutical strategies Inhaled sustained release formulations Local lung diseases Systemic diseases pulmonary safety

Increasing stiffness promotes pulmonary retention of ligand-directed dexamethasone-loaded nanoparticle for enhanced acute lung inflammation therapy

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Bioactive Materials 2023年第2期20卷 539-547页

作者： Yinglan Yu Shujie Li Yuan Yao Xinran Shen Lian Li Yuan Huang Key Laboratory of drug-Targeting and drug delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China

Inhaled nanoparticles(NPs)need to penetrate the bronchial mucosa to deliver drug payloads deeply in the lung for amplified local ***,the bronchial mucociliary barrier eliminates NPs rapidly,which considerably limits their mucosal *** this study,we find that surface ligand modification and stiffness adjustment of NPs contribute to the significantly enhanced bronchial mucosal absorption and pulmonary retention of inhaled *** utilize neonatal Fc receptor ligand(FcBP)to modify the rationally designed low stiffness NPs(Soft-NP)and high stiffness NPs(Stiff-NP)to target bronchial *** an acute lung inflammation rat model,after intranasal administration with dexamethasone-loaded NPs,Stiff-NP endowed with FcBP displays superior therapeutic *** in vitro data demonstrate that the promotion effect of FcBP to bronchial mucosal absorption of Stiff-NP dominates over *** could be attributed to the higher affinity between ligand-receptor when incorporating FcBP on the Stiff-NP ***,high stiffness modulates more actin filaments aggregation to mediate endocytosis,along with strengthened Ca2+signal to enhance ***,we highlight that FcBP-modified NPs with higher stiffness would be a potential pulmonary drug delivery system.

关键词： pulmonary drug delivery Mucus barrier Epithelial barrier Stiffness Ligand modification Acute lung inflammation

In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug

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Asian Journal of Pharmaceutical Sciences 2021年第3期16卷 350-362页

作者： Changzhi Shi Jelisaveta Ignjatovic Tingting Liu Meihua Han Dongmei Cun JelenaĐuriš Mingshi Yang Sandra Cvijic Wuya College of Innovation Shenyang Pharmaceutical UniversityWenhua Road No.103110016 ShenyangChina Department of Pharmaceutical Technology and Cosmetology University of Belgrade-Faculty of PharmacyVojvode Stepe 45011221 BelgradeSerbia Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenUniversitetsparken 2DK-2100 CopenhagenDenmark

This study aims to understand the absorption patterns of three different kinds of inhaled formulations via in silico modeling using budesonide(BUD)as a model *** formulations investigated in this study are:(i)commercially available micronized BUD mixed with lactose(BUD-PT),(ii)BUD nanocrystal suspension(BUD-NC),(iii)BUD nanocrystals embedded hyaluronic acid microparticles(BUD-NEM).The deposition patterns of the three inhaled formulations in the rats’lungs were determined in vivo and in silico predicted,which were used as inputs in GastroPlus TM software to predict drug absorption following aerosolization of the tested *** pharmacokinetics,estimated based on intravenous data in rats,was used to establish a drug-specific in silico absorption *** BUD-specific in silico model revealed that drug pulmonary solubility and absorption rate constant were the key factors affecting pulmonary absorption of BUD-NC and BUD-NEM,*** the case of BUD-PT,the in silico model revealed significant gastrointestinal absorption of BUD,which could be overlooked by traditional in vivo experimental *** study demonstrated that in vitro-in vivo-in silico approach was able to identify the key factors that influence the absorption of different inhaled formulations,which may facilitate the development of orally inhaled formulations with different drug release/absorption rates.

关键词： pulmonary drug delivery Budesonide Nanocrystal suspension Nanocrystal-embedded microparticles In silico physiologically-based pharmacokinetic modeling

Applications of the crystallization process in the pharmaceutical industry

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Frontiers of Chemical Science and Engineering 2010年第1期4卷 2-9页

作者： Sohrab ROHANI Department of Chemical and Biochemical Engineering University of Western OntarioLondonOntario N6A 5B9Canada

The applications of the crystallization technique in the pharmaceutical industry as a purification and separation process for the isolation and synthesis of pure active pharmaceutical ingredients(API),co-crystals,controlled release pulmonary drug delivery,and separation of chiral isomers are briefly discussed using a few case *** effect of process variables and solvent on the polymorphism and morphology of stavudine is *** implementation of external control in the form of feedback and real-time optimal control using cooling and antisolvent crystallization of paracetamol in water-isopropyl alcohol is *** methods to prepare micronsized drug particles,namely,micro-crystallization and polymer-coated API-loaded magnetic nanoparticles for pulmonary drug delivery,are *** significance of co-crystals in drug administration is highlighted using the theophylline-nicotinamide co-crystal *** of chloromandelic acid derivatives,a racemic compound,is achieved using direct crystallization and diastereomeric salts *** crystal structures of diastereomeric salts of chloromandelic acid and phenylethylamine are *** structure comparison between the less soluble and more soluble salts shows that weak interactions such as CH/πinteractions and van der Waals forces contribute to chiral recognition when the hydrogen bonding patterns are similar.

关键词： crystallization control of crystal properties polymorphism co-crystals pulmonary drug delivery resolution of chiral isomers

drug/polymer nanoparticles prepared using unique spray nozzles and recent progress of inhaled formulation

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Asian Journal of Pharmaceutical Sciences 2014年第5期9卷 236-243页

作者： Tetsuya Ozeki Tatsuaki Tagami drug delivery and Nano Pharmaceutics Graduate School of Pharmaceutical SciencesNagoya City University3-1 Tanabe-doriMizuho-kuNagoyaAichi 467-8603Japan

Inhaled formulations are promising for pulmonary and systemic non-pulmonary *** engineered particles including drugs and drug-loaded nanocarriers have been anticipated because they can improve drug delivery efficacy against target sites in the lungs or *** this review,unique spray nozzles(e.g.,four-fluid spray nozzle and twosolution mixing type nozzle)for the preparation of nanocomposite particles which mean microparticles containing drug nanoparticles are *** nozzles can produce nanocomposite particles in one-step and their spray drying system is suitable for *** particles are useful in improving drug absorption and delivery efficacy against alveolar *** addition,recent studies on several pulmonary diseases(tuberculosis,lung cancer,cystic fibrosis,pneumonia,vaccine and others)and related inhaled formulations were also reviewed.

关键词： pulmonary drug delivery Inhalation Lung diseases Spray drying One-step preparation of nanocomposite particles

pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy

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Asian Journal of Pharmaceutical Sciences 2023年第4期18卷 153-161页

作者： Yu Tang Lanfang Zhang Rui Sun Baiyi Luo Yu Zhou Yan Zhang Yuqi Liang Bo Xiao Chenhui Wang Chongqing Key Laboratory of Natural Product Synthesis and drug Research Innovative Drug Research CenterSchool of Pharmaceutical SciencesChongqing UniversityChongqing 401331China State Key Laboratory of Silkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing 400715China

The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin(marked as QR-SF(PF127)NPs),aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of *** PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins,thus facilitating the diffusion of SF(PF127)NPs in the mucus *** QR-SF(PF127)NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release *** recovery after photobleaching(FRAP)assay and transepithelial transport test showed that QR-SF(PF127)NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell ***,a large amount of QR-SF(PF127)NPs distributed uniformly in the mice airway section,indicating the good retention of NPs in the respiratory *** lungmetastasismodel was established,and the therapeutic effect of QR-SF(PF127)NPs was significantly improved in ***127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhancemucus penetration efficiency in the pulmonary drug delivery system.

关键词： pulmonary drug delivery Mucus penetration Quercetin Pluronic F127