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From oral formulations to drug-eluting implants:using 3D and 4D printing to develop drug delivery systems and personalized medicine

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Bio-Design and Manufacturing 2022年第1期5卷 85-106页

作者： Niels G.A.Willemen Margaretha A.J.Morsink Devin Veerman Classius F.da Silva Juliana C.Cardoso Eliana B.Souto Patrícia Severino Center for Biomedical Engineering Department of MedicineBrigham and Women&HospitalHarvard Medical School65 Landsdowne StreetMA 02139 CambridgeUSA Department of Developmental BioEngineering Faculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteEnschedeThe Netherlands Translational Liver Research Department of Medical Cell BioPhysicsTechnical Medical CentreFaculty of Science and TechnologyUniversity of TwenteEnschedeThe Netherlands Targeted Therapeutics Department of Biomaterials Science and TechnologyFaculty of Science and TechnologyUniversity of TwenteEnschedeThe Netherlands Department of Chemical Engineering Institute of EnvironmentalChemical and Pharmaceutical SciencesFederal University of São PauloRua São Nicolau210Diadema 09913‑030Brazil University of Tiradentes(Unit) and Institute of Technology and Research(ITP)Av.Murilo Dantas300Aracaju 49010‑390Brazil Faculty of Pharmacy University of CoimbraPólo das Ciências da SaúdeAzinhaga de Santa Comba3000‑548 CoimbraPortugal CEB‑Centre of Biological Engineering University of MinhoCampus de Gualtar4710‑057 BragaPortugal Tiradentes Institute 150 Mt Vernon StDorchesterMA 02125USA

Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown *** short,personalized medicine is a term that describes medical treatment that is tuned to the *** possible way to realize personalized medicine is 3D *** using materials that can be tuned upon stimulation,4D printing is *** recent years,many studies have been exploring a new field that combines 3D and 4D printing with *** has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an ***,the first 3D printed drug,Spritam®,has already found its way to the *** review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.

关键词： drug delivery systems 3D/4D printing drug-eluting implants Microneedles Oral formulations

Binding and conformation of dendrimer-based drug delivery systems:a molecular dynamics study

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Advances in Manufacturing 2015年第3期3卷 221-231页

作者： Fa-Da Zhang Yi Liu Jing-Cheng Xu Sheng-Juan Li Xiu-Nan Wang Yue Sun Xin-Luo Zhao Department of Physics and Materials Genome Institute Shanghai University School of Materials Science and Engineering University of Shanghai for Science and Technology School of Energy & Power Engineering University of Shanghai for Science and Technology

All atomistic molecular dynamics simulations were performed on poly （amidoamine）（PAMAM） dendrimers that compound non-covalently with anticancer drug molecules including DOX, MTX, CE6, and SN38. The binding energies as well as their associated interaction energies and deformation energies were combined to evaluate the relative binding strength among drug, PAMAM, and PEG chains. We find that the deformation of dendrimers due to drug loading plays a crucial role in the drug binding. It is energetically favorable for the drug molecules to bind with PAMAM while the drugs bind with PEG metastable chains via kinetic confinement. Surface PEGylation helps dendrimers to accommodate more drug molecules with greater strength without inducing too much expansion. This work indicates that tuning the functionalized terminal groups of dendrimers is critical to design efficient dendrimer-based drug delivery systems.

关键词： Dendrimer PAMAM - PEGylation-Anticancer drug drug delivery systems Moleculardynamics

pH-Sensitive nanoscale materials as robust drug delivery systems for cancer therapy

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Chinese Chemical Letters 2020年第6期31卷 1345-1356,F0003页

作者： Zhaoqing Shi Qianqian Li Lin Mei School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityShenzhen 518107China Tsinghua Shenzhen International Graduate School.Tsinghua University Shenzhen 518055China

Cancer is one of the diseases that have the highest mortality,which threatens the human *** functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side *** to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and ***,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer ***,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug *** summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.

关键词： Cancer therapy drug delivery systems Nanoparticles pH-sensitive material

Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy:A review of recent advances

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Chinese Chemical Letters 2024年第8期35卷 128-137页

作者： Ningyue Xu Jun Wang Lei Liu Changyang Gong Division of Head&Neck Tumor Multimodality Treatment Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor *** overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic *** review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer ***,we introduce the classification and properties of ***,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and *** also discuss hydrogels used in combination therapy involving RT and ***,we highlight the challenges that hydrogels face in *** surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.

关键词： Radiotherapy drug delivery systems Hydrogel Radiation sensitization Combination therapy

Dynamic covalent chemistry-regulated stimuli-activatable drug delivery systems for improved cancer therapy

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Chinese Chemical Letters 2020年第5期31卷 1051-1059页

作者： Qiwen Zhu Madiha Saeed Rundi Song Tao Sun Chen Jiang Haijun Yu State Key Laboratory of drug Research&1 Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Key Laboratory of Smart drug delivery(Ministry of Education).State Key Laboratory of Medical Neurobiology.Department of Pharmaceutics School of Pharmacy.Fudan University.Shanghai 201203China University of Chinese Academy of Sciences.Beijing 100049 China

drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical ***,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug *** chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release *** review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer *** review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and ***,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.

关键词： Cancer therapy drug delivery systems Dynamic covalent chemistry Acid-responsive Reduction-responsive

Challenges in cell membrane-camouflaged drug delivery systems:Development strategies and future prospects

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Chinese Chemical Letters 2021年第8期32卷 2347-2358页

作者： Xinlong Liu Xin Zhong Chong Li College of Pharmaceutical Sciences Southwest UniversityChongqing 400715China

Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent ***,we provide an overview of the challenges in system preparation,functional design,continuous industrial production of these systems,and solution strategies for these ***,we analyze and discuss the frontier medical applications of cell membrane-camouflaged drug delivery systems in anti-inflammatory,anti-pathogenic microorganisms,and biological *** review takes a challenge-oriented perspective and seeks innovative strategies,provides a literature review of research into cell membrane-camouflaged drug delivery systems,and promotes the development of personalized clinical treatments.

关键词： Cell membrane materials drug delivery systems Multi-functionality Active targeting Biological detoxification

Preparation of Tris（2-aminoethyl）amine-Cross-Linked Cyclodextrin-Based Porous Nanospheres and Their Application as drug delivery systems

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Chinese Journal of Chemistry 2013年第5期31卷 657-662页

作者： Youqing Wang Yanchao Zhao Baohang Han National Center for Nanoscience and Technology Beijing 100190 China

Cyclodextrins （CDs） show functionality, biocompatibility, and host-guest inclusion capacity with a variety of molecules. These unique properties offer great potential for the exploitation of CDs as drug delivery systems. An easy, green, and effective synthetic approach was described to develop CD-based porous nanospheres （CDPNSs） with a size distribution from 100 to 400 nm. A new cross-linker tris（2-aminoethyl）amine was used to cross-link modified β-CD at room temperature. The resulting CD-based polymers （CDPs） were reshaped from a random mor- phology into a spherical shape during a dialysis process, and CDPNSs were obtained. The morphologies of CDPs and CDPNSs were observed with scanning electron microscopy. The average diameter and the size distribution of CDPNSs were determined by dynamic light scattering. The structures of the resulting products were characterized by using Fourier transform infrared spectroscopy, 1H NMR spectroscopy, solid-state 13C CP/MAS NMR spectro- scopy, and X-ray diffraction. Furthermore, a study was conducted on drug loading and in vitro release behavior of CDPNSs, which was monitored by ultraviolet spectroscopy. The prepared CDPNSs show the potential as drug de- livery systems.

关键词： cyclodextrins cross-linking porous nanospheres drug delivery systems

Recent advances in drug delivery systems for targeting cancer stem cells

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Acta Pharmaceutica Sinica B 2021年第1期11卷 55-70页

作者： Hongxia Duan Yanhong Liu Zhonggao Gao Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of drug delivery Technology and Novel Formulations Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem *** few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation *** addition,CSCs have the ability to escape immune ***,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after ***,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under *** the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being *** this review,we summarize the advances in CSC-targeted ***,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.

关键词： Cancer stem cells Targeting strategies drug delivery systems Cancer treatment Niche Biomarker Cellular level Molecular level

A review on phospholipids and their main applications in drug delivery systems

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Asian Journal of Pharmaceutical Sciences 2015年第2期10卷 81-98页

作者： Jing Li Xuling Wang Ting Zhang Chunling Wang Zhenjun Huang Xiang Luo Yihui Deng School of Pharmacy Shenyang Pharmaceutical UniversityNo.103Wenhua RoadShenyang 110016China

Phospholipids have the characteristics of excellent biocompatibility and a especial *** unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery *** aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug *** refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery *** present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.

关键词： Phospholipids Biocompatibility Amphiphilicity drug delivery systems