Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative disorders include Alzheimer’s and Parkinson’s disease. Although there are several medicines currently approved for managing neurodegenerative disorders, a large majority of them only help with associated symptoms. This lack of pathogenesis-targeting therapies is primarily due to the restrictive effects of the blood–brain barrier (BBB), which keeps close to 99% of all “foreign substances” out of the brain. Since their discovery, nanoparticles have been successfully used for targeted delivery into many organs, including the brain. This review briefly describes the pathophysiology of Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis, and their current management approaches. We then highlight the major challenges of brain-drug delivery, followed by the role of nanotherapeutics for the diagnosis and treatment of various neurological disorders.
Layer-by-layer deposition of cells, tissues and similar molecules provided by additive manufacturing techniques such as 3D bioprinting offers safe, biocompatible, effective and inert methods for the production of biological structures and biomimetic scaffolds. 3D bioprinting assisted through computer programmes and software develops mutli-modal nano-or micro-particulate systems such as biosensors, dosage forms or delivery systems and other biological scaffolds like pharmaceutical implants, prosthetics, etc. This review article focuses on the implementation of 3D bioprinting techniques in the gene expression, in gene editing or therapy and in delivery of genes. The applications of 3D printing are extensive and include gene therapy, modulation and expression in cancers, tissue engineering, osteogenesis, skin and vascular regeneration. Inclusion of nanotechnology with genomic bioprinting parameters such as gene conjugated or gene encapsulated 3D printed nanostructures may offer new avenues in the future for efficient and controlled treatment and help in overcoming the limitations faced in conventional methods. Moreover, expansion of the benefits from such techniques is advantageous in real-time delivery or in-situ production of nucleic acids into the host cells.
The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.
Multifunctional fatty acid grafted polymeric micelles are an effective and promising approach for drug and gene delivery to the brain. An alternative approach to bypass the blood–brain barrier is administration through intranasal route. Multifunctional fatty acid grafted polymeric micelles were prepared and characterized for pVGF delivery to the brain. In vitro pVGF expression was analyzed in bEnd.3 cells, primary astrocytes, and neurons. Comparative in-vivo pVGF expression was analyzed to evaluate the effective route of administration between intranasal and intravenous. Biocompatible, multifunctional polymeric micelles were prepared, having an average size of 200 nm, and cationic zeta potential. Modified polymers were found to be hemo- and cyto-compatible. When transfected with the different modified chitosan formulations, significantly (p < 0.05) higher VGF expression was observed in primary astrocytes and neurons using the mannose, Tat peptide, and oleic acid grafted chitosan polymer. Compared to intravenous administration, intranasal administration of pVGF in polyplex formulation led to significantly (p < 0.05) higher pVGF expression. Developed multifunctional polymeric micelles were an effective pVGF delivery platform to the brain. Mannose and Tat ligand tagging improved the pVGF delivery to the brain.
Epilepsy is a common but a complex neurological disorder with limited practices for successful management due to the complicated neuronal network and lack of knowledge of epileptic pathophysiology. Theranostic systems such as implantable devices and biodegradable nanomaterials offer better tailor‐made methods for the detection and treatment using nanotechnology‐based approaches for patients with epilepsy. Miniaturized nano‐implantable devices and biosensors equipped with operations to mimic neurostimulation demonstrate excellent opportunities in profiling the disease and assist in comprehension of the relationship between the disease and host. This strategy is developed for diagnoses and mapping brain activities to integrate and target therapeutic nanosystems in epilepsy. Non‐invasive class of nanotheranostics such as biodegradable and stimuli‐responsive polymers includes nanomaterials that utilize bio‐physico‐chemical processes or stimuli as a source for detecting the state and progress of the disease. The superior form of nanotheranostics encompasses in‐situ diagnostics with triggered release at the specific site. This review article focuses on the nanotheranostic strategies for epilepsy, their implications, challenges and new potentials for detection and therapy in personalized medicine. The concept of “on‐demand” release of drugs at the site of action using bio‐responsive theranostic approach reveals a potential for developing a point of primary care for epilepsy in the future.
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for efficient SARS coronavirus 2 (SARS-CoV-2) preventative vaccines to limit the burden and spread of SARS-CoV-2 in humans. Intranasal immunization is a promising technique for preventing COVID-19 because the nasal mucosa acts as a first line of defense against SARS-CoV-2 entrance before the virus spreads to the lungs. Nasal vaccination has many advantages over traditional vaccine administration methods. These include the simplicity of administration without the use of needles, which decreases the risks of needle stick injuries and disposal. This channel also provides simple access to a crucial portion of the immune system that can stimulate other mucosal sites throughout the body. By targeting immunoglobulin A (IgA), antibodies found only in the mucosa, an intranasal vaccination would elicit immunological responses in the nose, throat, and lungs. Potential pathogens are trapped by the mucosa, which acts as a physical barrier to prevent them from entering the body. Given this, the intranasal vaccine would prevent virus transmission via exhaled droplets or aerosols because there would be no virus in the body to expel .There are several intranasal vaccines for protection against sars-cov2 are under preclinical and clinical trials .The key challenge is in Designing delivery strategies that take into account the wide range of diseases, populations, and healthcare delivery settings that stand to benefit from this unique mucosal route should be prioritized. Keywords: COVID-19, Intranasal vaccine, Immunoglobulin A, Permeation
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