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Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders

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Acta Pharmaceutica Sinica B 2023年第5期13卷 1866-1886页

作者： Rania Awad Avi Avital Alejandro Sosnik Laboratory of Pharmaceutical Nanomaterials Science Department of Materials Science and EngineeringTechnion-Israel Institute of TechnologyHaifa 3200003Israel Behavioral Neurobiology Laboratory Department of Occupational TherapyFaculty of Social Welfare and Health SciencesUniversity of HaifaHaifa 3498838Israel

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.

关键词： Neurodegenerative diseases Neurodevelopmental disorders Central nervous system Blood—brain barrier Nano-drug delivery systems Nose-to-brain pathway Intranasal administration Polymeric nanoparticles Polymeric micelles Dendrimers

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Editorial of Special Column on Delivery Nanotechnologies to Modulate the Immune System and Combat Inflammation and Infection

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药学学报:英文版 2023年第6期13卷 2296-2297页

作者： Wei He Alejandro Sosnik Chenjie Xu School of Pharmacy China Pharmaceutical UniversityNanjing 211198China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China Laboratory of Pharmaceutical Nanomaterials Science Department of Materials Science and EngineeringTechnion-Israel Institute of TechnologyHaifa 3200003Israel Department of Biomedical Engineering City University of Hong KongHong Kong 999077China

Our immune system has a vital role,and any variation because of either heritable or non-heritable stimuli might cause health disorders such as cancer,diabetes,and cardiovascular diseases1.In addition,the complexity of the anatomical barriers,such as the blood brain barrier,challenges the therapy of central nervous system(CNS)diseases.The goal of nano-dimensional drugs(nanomedicines)is to improve the efficacy of treatments while minimizing systemic toxicity and side effects.

关键词： drugs cardiovascular Immune

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Electrospun poly（vinylidene fluoride-trifluoroethylene）/ zinc oxide nanocomposite tissue engineering scaffolds with enhanced cell adhesion and blood vessel formation

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Nano Research 2017年第10期10卷 3358-3376页

作者： Robin Augustine Pan Dan Alejandro Sosnik Nandakumar Kalarikkal Nguyen Tran Brice Vincent Sabu Thomas Patrick Menu Didier Rouxel Laboratory of Pharmaceutical Nanomaterials Science Department of Materials Science and Engineering Technion-lsrael Institute of Technology De-Jur Building Technion City Haifa 3200003 Israel Intemationaland Inter University Centre for Nanoscience and Nanotechnology Mahatma Gandhi University Kottayam Kerala 686560 India Ingenierie Moleculaire et Physiopathologie Articulaire UMR 7365 CNRS-Universite de Lorraine Vandoeuvre-Ies Nancy F-54500 France School of Pure and Applied Physics Mahatma Gandhi University Kottayam Kerala 686560 India School of Surgery Faculty of Medicine Universite de Lorraine Vandoeuvre-Ies-Nancy F-54500 France Institut Jean Lamour UMR 7198 CNRS-Universite de Lorraine Vandoeuvre-Ies-Nancy F-54500 France School of Chemical Sciences Mahatma Gandhi University Kottayam Kerala 686560 India

Piezoelectric materials that generate electrical signals in response to mechanical strain can be used in tissue engineering to stimulate cell proliferation. Poly （vinylidene fluoride-trifluoroethylene）（P（VDF-TrFE））, a piezoelectric polymer, is widely used in biomaterial applications. We hypothesized that incorporation of zinc oxide （ZnO） nanoparticles into the P（VDF-TrFE） matrix could promote adhesion, migration, and proliferation of cells, as well as blood vessel formation （angiogenesis）. In this study, we fabricated and comprehensively characterized a novel electrospun P（VDF-TrFE）/ZnO nanocomposite tissue engineering scaffold. We analyzed the morphological features of the polymeric matrix by scanning electron microscopy, and utilized Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry to examine changes in the crystalline phases of the copolymer due to addition of the nanoparticles. We detected no or minimal adverse effects of the biomaterials with regard to blood compatibility in vitro, biocompatibility, and cytotoxicity, indicating that P（VDF-TrFE）/ZnO nanocomposite scaffolds are suitable for tissue engineering applications. Interestingly, human mesenchymal stem cells （hMSCs） and human umbilical vein endothelial cells cultured on the nanocomposite scaffolds exhibited higher cell viability, adhesion, and proliferation compared to cells cultured on tissue culture plates or neat P（VDF-TrFE） scaffolds. Nanocomposite scaffolds implanted into rats with or without hMSCs did not elicit immunological responses, as assessed by macroscopic analysis and histology. Importantly, nanocomposite scaffolds promoted angiogenesis, which was increased in scaffolds pre-seeded with hMSCs. Overall, our results highlight the potential of these novel P（VDF-TrFE）/ZnO nanocomposites for use in tissue engineering, due to their biocompatibility and ability to promote cell adhesion and angiogenesis.

关键词： scaffolds electrospinning poly（vinylidene fluoride-trifluoroethylene）（P（VDF-TrFE）） ZnO angiogenesis cell adhesion stem cells

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Stimulating Extracellular Vesicles Production from Engineered Tissues by Mechanical Forces

Stimulating Extracellular Vesicles Production from Engineere...

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2021海峡两岸暨港澳精准医学青年博士论坛

作者： Shaowei Guo Lior Debbi Barak Zohar Roee Samuel Roni S.Arzi Adina I.Fried Tahel Carmon Dudi Shevach Idan Redenski Inbar Schlachet Alejandro Sosnik Shulamit Levenberg Faculty of Biomedical Engineering Technion-Israel Institute of Technology The First Affiliated Hospital Shantou University Medical College Laboratory of Pharmaceutical Nanomaterials Science Department of Material Science and Engineering Technion-Israel Institute of Technology

Background: Extracellular vesicles (EVs) have emerged as a promising strategy to promote tissue regeneration. However, overcoming the low EV production yield remains a big challenge in translating EV-based therapies to the clinical practice. Current EV production relies heavily on 2D cell culture, which is not only less physiologically relevant to cells, but also requires substantial medium and space. Therefore, we aimed to boost EVs secretion by a novel method combining tissue engineering and biomechanics.

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