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

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.

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

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.

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

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.