Gut instincts: Unveiling the connection between gut microbiota and Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder marked by neuroinflammation and gradual cognitive decline. Recent research has revealed that the gut microbiota (GM) plays an important role in the pathogenesis of AD through the microbiota-gut-brain axis. However, the mechanism by which GM and microbial metabolites alter brain function is not clearly understood. GM dysbiosis increases the permeability of the intestine, alters the blood-brain barrier permeability, and elevates proinflammatory mediators causing neurodegeneration. This review article introduced us to the composition and functions of GM along with its repercussions of dysbiosis in relation to AD. We also discussed the importance of the gut-brain axis and its role in communication. Later we focused on the mechanism behind gut dysbiosis and the progression of AD including neuroinflammation, oxidative stress, and changes in neurotransmitter levels. Furthermore, we highlighted recent developments in AD management, such as microbiota-based therapy, dietary interventions like prebiotics, probiotics, and fecal microbiota transplantation. Finally, we concluded with challenges and future directions in AD research based on GM.

From lab to ecosystem: Understanding the ecological footprints of engineered nanoparticles.

Nanotechnology has attained significant attention from researchers in past decades due to its numerous advantages, such as biocompatibility, biodegradability, and improved stability over conventional drug delivery systems. The fabrication of engineered nanoparticles (ENPs), including carbon nanotubes (CNTs), fullerenes, metallic and metal oxide-based NPs, has been steadily increasing day due to their wide range of applications from household to industrial applications. Fabricated ENPs can release different materials into the environment during their fabrication process. The effect of such materials on the environment is the primary concern with due diligence on the safety and efficacy of prepared NPs. In addition, an understanding of chemistry, reactivity, fabrication process, and viable mechanism of NPs involved in the interaction with the environment is very important. To date, only a limited number of techniques are available to assess ENPs in the natural environment which makes it difficult to ascertain the impact of ENPs in natural settings. This review extensively examines the environmental effects of ENPs and briefly discusses useful tools for determining NP size, surface charge, surface area, and external appearance. In conclusion, the review highlights the potential risks associated with ENPs and suggests possible solutions.

Exploring the potential of pH-sensitive polymers in targeted drug delivery.

The pH-sensitive polymers have attained significant attention in the arena of targeted drug delivery (TDD) because of their exceptional capability to respond to alteration in pH in various physiological environments. This attribute aids pH-sensitive polymers to act as smart carriers for therapeutic agents, transporting them precisely to target locations while curtailing the release of drugs in off-targeted sites, thereby diminishing side effects. Many pH-responsive polymers in TDD have revealed promising results, with increased therapeutic efficacy and decreased toxic effects. Several pH-sensitive polymers, including, hydroxy-propyl-methyl cellulose, poly (methacrylic acid) (Eudragit series), poly (acrylic acid), and chitosan, have been broadly studied for their myriad applications in the management of various types of diseases. Additionally, the amalgamation of pH-sensitive polymers with, additive manufacturing techniques like 3D printing, has resulted in the progression of novel drug delivery systems that regulate drug release in a controlled manner. Herein, types of pH-sensitive polymers in TDD are systemically reviewed. We have briefly discussed the nanocarriers employed for the delivery of various pH-sensitive polymers in TDD. Finally, miscellaneous applications of pH-sensitive polymers are discussed thoroughly with special attention to the implication of 3D printing in pH-sensitive polymers.

Empowering the Battle: Bioenhancers as Allies against Cancer Drug Resistance.

BACKGROUND: Drug resistance has been a great hindrance in the path of counteracting diseases like cancer and is driven by drugs misuse and overuse. In terms of cancer, resistance has been developed due to cellular changes, altered growth activation pathways, increased expression of efflux proteins, and changes in the local physiology of cancer (blood supply, tissue hydrodynamics, increased mutation rate/epigenetics, tumor cell heterogeneity). One of the approaches to address these challenges is the use of bioenhancers, which can overcome drug resistance, thereby improving bioavailability (BA). CONCLUSION: Bioenhancers when combined with drugs can elicit pharmacological activity. They are generally combined with therapeutic agents at low doses, which increase the BA or therapeutic activity of active pharmaceutical ingredient (API). This review sheds light on the synthesis and classification of bio-enhancers. It also discusses different applications of bio-enhancers like piperine, ginger, quercetin, curcumin, etc. in the treatment of cancer. The review also presents some of the recent advancements in terms of nanocarriers for delivering API combined with bioenhancers.

Functionalized liposomes: an enticing nanocarrier for management of glioma.

Glioma is one of the most severe central nervous systems (CNS)-specific tumors, with rapidly growing malignant glial cells accounting for roughly half of all brain tumors and having a poor survival rate ranging from 12 to 15 months. Despite being the most often used technique for glioma therapy, conventional chemotherapy suffers from low permeability of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) to anticancer drugs. When it comes to nanocarriers, liposomes are thought of as one of the most promising nanocarrier systems for glioma treatment. However, owing to BBB tight junctions, non-targeted liposomes, which passively accumulate in most cancer cells primarily via the increased permeability and retention effect (EPR), would not be suitable for glioma treatment. The surface modification of liposomes with various active targeting ligands has shown encouraging outcomes in the recent times by allowing various chemotherapy drugs to pass across the BBB and BBTB and enter glioma cells. This review article introduces by briefly outlining the landscape of glioma, its classification, and some of the pathogenic causes. Further, it discusses major barriers for delivering drugs to glioma such as the BBB, BBTB, and tumor microenvironment. It further discusses modified liposomes such as long-acting circulating liposomes, actively targeted liposomes, stimuli responsive liposomes. Finally, it highlighted the limitations of liposomes in the treatment of glioma and the various actively targeted liposomes undergoing clinical trials for the treatment of glioma.

Gut microbiota and traumatic central nervous system injuries: Insights into pathophysiology and therapeutic approaches.

Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate in death or cognitive and motor impairment. Over the past decade, researchers have tapped into research to discover the potential role being played by gut bacteria in CNS. After an acute CNS injury, the altered composition of the gut microbiota disturbs the balance of the bidirectional gut-brain axis, aggravating secondary CNS injury, motor dysfunctions, and cognitive deficits, which worsens the patient's prognosis. Some of the well-known therapeutic interventions which can also be used as adjuvant therapy for alleviating CNS injuries include, the use of pro and prebiotics, fecal microbiota transplantation, and microbial engineering. In this review, we aim to discuss the importance of gut microbes in our nervous system, anatomy, and signaling pathways involved in regulating the gut-brain axis, the alteration of the gut microbiome in CNS injuries, and the therapeutic strategies to target gut microbiomes in traumatic CNS injuries.

Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer.

BACKGROUND: Exosomes are nanosized bio vesicles formed when multivesicular bodies and the plasma membrane merge and discharge into bodily fluids. They are well recognized for facilitating intercellular communication by transporting numerous biomolecules, including DNA, RNAs, proteins, and lipids, and have been implicated in varied diseases including cancer. Exosomes may be altered to transport a variety of therapeutic payloads, including as short interfering RNAs, antisense oligonucleotides, chemotherapeutic drugs, and immunological modulators, and can be directed to a specific target. Exosomes also possess the potential to act as a diagnostic biomarker in cancer, in addition to their therapeutic potential. CONCLUSION: In this review, the physiological roles played by exosomes were summarized along with their biogenesis process. Different isolation techniques of exosomes including centrifugation-based, size-based, and polymer precipitation-based techniques have also been described in detail with a special focus on cancer therapeutic applications. The review also shed light on techniques of incubation of drugs with exosomes and their characterization methods covering the most advanced techniques. Myriad applications of exosomes in cancer as diagnostic biomarkers, drug delivery carriers, and chemoresistance-related issues have been discussed at length. Furthermore, a brief overview of exosome-based anti-cancer vaccines and a few prominent challenges concerning exosomal delivery have been concluded at the end.

In vitro-in vivo correlation in nanocarriers: From protein corona to therapeutic implications.

Understanding and establishing a link between the physicochemical characteristics of nanoparticles (NPs) and their biological interactions poses to be a great challenge in the field of nanotherapeutics. Recent analytical advancements concerning bio-nanointerfaces have accelerated the quest to comprehend the fate of nanocarrier systems in vivo. Scientists have discovered that protein corona, an adsorbed layer of biomolecules on the surface of NPs takes a leading part in interacting with cells and in the cellular uptake process, thereby determining the in vivo behaviour of NPs. Another useful method to assess the in vivo fate of NPs is by performing dissolution testing. This forms the basis for in vitro in vivo correlation (IVIVC), relating in vitro dissolution of NPs and their in vivo properties. Scientists are continuously directing their efforts towards establishing IVIVC for different nanocarrier systems while concurrently gaining insights into protein corona. This review primarily summarizes the importance of protein corona and its interaction with nanoparticles. It also gives an insight into the factors affecting the interaction and various in vitro dissolution media used for varied nanocarrier systems. The article concludes with a discussion of the limitations of IVIVC modelling and its position from a regulatory perspective.

Recent advances of polymer based nanosystems in cancer management.

Cancer is still one of the leading causes of death worldwide. Nanotechnology, particularly nanoparticle-based platforms, is at the leading edge of current cancer management research. Polymer-based nanosystems have piqued the interest of researchers owing to their many benefits over other conventional drug delivery systems. Polymers derived from both natural and synthetic sources have various biomedical applications due to unique qualities like porosity, mechanical strength, biocompatibility, and biodegradability. Polymers such as poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and polyethylene glycol (PEG) have been approved by the USFDA and are being researched for drug delivery applications. They have been reported to be potential carriers for drug loading and are used in theranostic applications. In this review, we have primarily focused on the aforementioned polymers and their conjugates. In addition, the therapeutic and diagnostic implications of polymer-based nanosystems have been briefly reviewed. Furthermore, the safety of the developed polymeric formulations is crucial, and we have discussed their biocompatibility in detail. This article also discusses recent developments in block co-polymer-based nanosystems for cancer treatment. The review ends with the challenges of clinical translation of polymer-based nanosystems in drug delivery for cancer therapy.

Emerging theranostics to combat cancer: a perspective on metal-based nanomaterials.

OBJECTIVE: Theranostics, encompassing diagnostics and therapeutics, has emerged as a critical component of cancer treatment. Metal-based theranostics is one such next-generation nanotechnology-based drug delivery system with a myriad of benefits in pre-clinical and clinical medication for the deadly diseases like cancer, where early detection can actually be life-saving. SIGNIFICANCE: Metal theranostics have shown promising outcomes in terms of anticancer medication monitoring, targeted drug delivery, and simultaneous detection and treatment of early-stage cancer. METHODS: For collection of literature data, different search engines including Google scholar, SciFinder, PubMed, ScienceDirect have been employed. With key words like, cancer, theranostics, metal nanoparticles relevant and appropriate data have been generated. RESULTS: Noninvasive administration of the active drug is made possible by theranostics nanoparticulate systems' ability to aggregate at the tumor site and offer morphological and biochemical characteristics of the tumor site. The recent advancement of metal-based theranostics including metallic nanoparticles, metal oxides, metal sulfides, nanocomposites, etc. has been explored at length in this article. CONCLUSION: The review highlights emerging applications in terms of molecular imaging, targeted therapy and different diagnostic approaches of metal theranostics. Possible challenges faced by nanotheranostics in terms of clinical immersion and toxicological aspects which need to be addressed at depth are also discussed at the end.

Recent trends of bioconjugated nanomedicines through nose-to-brain delivery for neurological disorders.

The global burden of neurological disorders has been increasing day by day which calls for immediate attention to the solutions. Novel drug delivery systems are one of the alternatives that we count on to counteract these disorders. As the blood-brain barrier creates a significant hindrance to the delivery of drugs across the endothelium lining of the brain, nose-to-brain delivery has been the favorite option to administer such drugs. In recent times, bioconjugation has been viewed as a rapidly growing area in the field of pharmaceuticals. The pharmaceutical industry and academic research are investing significantly in bioconjugated structures as an attractive and advantageous potential aid to nanoparticulate delivery systems, with all of its flexible benefits in terms of tailor grafting and custom design as well as overcoming the majority of their drawbacks. This review discusses drug delivery via the intranasal route and gives insight into bioconjugation systems for drug molecules, their chemistry, and benefits over other systems. Conjugation of drugs/macromolecules with peptides, carbohydrates, ligands, and nucleic acids has also been discussed in detail. The figure represents few types of novel drug delivery systems and molecules that have been attempted by researchers for nose-to-brain delivery through nasal (mucosal) route for the effective management of epilepsy, Alzheimer's disease, brain cancer, and other brain disorders.