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.

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.

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.

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.

A Review on Edible Vaccines and Biopharmaceutical Products from Plants.

Plants have substantial potential for the development of various biopharmaceuticals. Plants provide a cost-effective and direct source for the production of biopharmaceuticals such as vaccines, antibodies, proteins, enzymes, and hormones. In most cases, purification is an important and expensive step in the production of these substances. The problem can be resolved when it is produced in plants and the whole plant can be consumed. Direct ingestion of plant materials may help in overcoming the purification step. Being produced in seeds, fruits and tubers, it helps in providing more immunization in developing countries at a cheaper rate. Moreover, it can be administered more efficiently than any other dosage forms. This review focuses on various immunization and therapeutic products that are produced in plants along with currently available formulations in each category.

Understanding the role of endothelial cells in brain tumor formation and metastasis: a proposition to be explored for better therapy.

Glioblastoma is one of the most devastating central nervous system disorders. Being a highly vascular brain tumor, it is distinguished by aberrant vessel architecture. This lends credence to the idea that endothelial cells (ECs) linked with glioblastoma vary fundamentally from ECs seen in the healthy human brain. To effectively design an antiangiogenic treatment, it is crucial to identify the functional and phenotypic characteristics of tumor-associated ECs. The ECs associated with glioblastoma are less prone to apoptosis than control cells and are resistant to cytotoxic treatments. Additionally, ECs associated with glioblastoma migrate more quickly than control ECs and naturally produce large amounts of growth factors such as endothelin-1, interleukin-8, and vascular endothelial growth factor (VEGF). For designing innovative antiangiogenic drugs that particularly target tumor-related ECs in gliomas, it is critical to comprehend these distinctive features of ECs associated with gliomas. This review discusses the process of angiogenesis, other factors involved in the genesis of tumors, and the possibility of ECs as a potential target in combating glioblastoma. It also sheds light on the association of tumor microenvironment and ECs with immunotherapy. This review, thus gives us the hope that neuro endothelial targeting with growth factors and angiogenesis regulators combined with gene therapy would open up new doorways and change our traditional perspective of treating cancer.

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.

Meropenem-Loaded Nanostructured Lipid Carriers For Skin and Soft Tissue Infection Caused by Staphylococcus aureus: Formulation, Design, and Evaluation.

AIM: Meropenem hydrochloride (MpM)-loaded nanostructured lipid carriers were designed for the effective management of skin infection caused by Staphylococcus aureus via topical route. The solvent evaporation tactic was preferred to develop nanostructured lipid carriers (NLCs). Stearic acid was used as a solid fatty acid; oleic acid was used as liquid fatty acid and Tween 80 as a surfactant. The Staphylococcus aureus burden was analyzed by pharmacodynamic studies. The skin retention was analyzed by fluorescence microscopy. Spherical shape of NLCs was confirmed by TEM. The optimum particle size of the MpM-NLCs was ~ 126.5 ± 0.9 nm with 79.1 ± 2.3% entrapment (EE) and 0.967 mV zeta potential. The in vitro release studies revealed 81.5 ± 3.1% release of drug in 48 h, while the pure drug was almost completely released (98.4 ± 1.4%) within 24 h confirming the potential of NLCs for sustained topical drug delivery. Skin permeation study also revealed better permeation of drug from NLCs than of plain drug. The prepared MpM-NLCs when stored at 4 ± 2°C for 90 days were found to be more stable when the formulation was stored at 28 ± 2°C. The S. aureus burden was analyzed by evaluating the zone of inhibition (ZOI). The ZOI of MpM alone and MpM-NLC gel was measured and compared with that of the control group. The MpM was found significantly effective when its gel was prepared with NLCs because of its enhanced adhesion property occlusion and ability to sustain release. In overall, the study's outcomes validated the relevance of NLC's composition as a vehicle for topical MpM administration in skin diseases caused by Staphylococcus aureus.

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.

Biomedical applications and toxicities of carbon nanotubes.

Carbon nanotubes are newer generation material broadly emerged for biomedical applications due to its tempting properties such as size and aspect ratio covering surface area to the length, electrical, mechanical and thermal properties in addition to their unique architecture. The view for CNT-based nanomedicines is attractive and promising. Carbon nanotubes compared to other nanocarriers can be easily modified for conjugation of bioactive compounds and ligands for targeting. The applications of carbon nanotubes are not only limited to drug delivery but also in diagnostic applications. Due to a variety of applications in drug delivery, it is necessary to bear in mind the toxicities of carbon nanotubes and catch the way to overcome the problems related to toxicities. Currently, many studies have explored the biodegradation mechanism of carbon nanotubes. Biodegradation shows a conspicuous pathway that enables degradation and removal of CNTs from living body and catalyzes the release of the load from the CNTs. Many articles have been published till date which evidentiary provides the promising applications of CNTs. The present review seeks to provide an overview on intracellular fate, applications and toxicities of CNTs.

Minicapsules encapsulating nanoparticles for targeting, apoptosis induction and treatment of colon cancer.

Cancer therapies are aimed at eliminating the rapidly growing tumor cells by surgery and radiotherapy. The present therapies are only fruitful in early identified cases. The present study involves the preparation and characterization of eudragit S100-coated mini-capsules filled with chitosan nanoparticles-unconjugated and folic acid (FA)-conjugated encapsulating caspase 3 activator (7-hydroxystaurosporine). The formulated nanoparticles were compared for the cancer targeting and curing ability of the same by pre-investigation through drug release in organ-imitated fluids and ex vivo studies (cell viability, DNA fragmentation, caspase 3 activity), and then its confirmation through in vivo studies (tumor regression and distribution). The prepared nanoparticles were nearly spherical in shape, having positive zeta potential. From the cell line studies, it can be concluded that both the conjugated formulations showed better uptake, apoptosis, caspase 3 activation and DNA fragmentation. Stability study was performed according to ICH guidelines and formulation stored at 5° ± 3 °C was found to be most stable. The in vivo studies also supported the findings and showed better comprehensive residence time (23.61 ± 1.75 h), tumor distribution profile than UCN 01 alone. The results of in vitro, ex vivo and in vivo studies lead to the conclusion that the coated minicapsules specifically deliver the drug in the colon showing high therapeutic value and low side effects.

Topical Delivery of Erythromycin Through Cubosomes for Acne.

BACKGROUND: Topical delivery is an attractive route for local and systemic treatment. The novel topical application has many advantages like averting the GI-irritation, preventing the metabolism of drugs in the liver and increasing the bioavailability of the drug over the conventional dosage forms. OBJECTIVE: The aim of present work was to prepare and characterized erythromycin encapsulated cubosomes using different concentrations of glyceryl monooleate and poloxamer 407 by the emulsification method. METHODS: The prepared dispersion of cubosomes was characterized for surface morphology, particle size, entrapment efficiency and in vitro release. Further, optimized formulation was converted to cubosomal gel by incorporating carbopol 934 at different concentrations. The prepared gel was characterized for homogeneity, pH, viscosity, spreadibility, drug content and in vitro drug release study. RESULTS: The result of optimized cubosomes showed average particle size of 264.5±2.84nm and entrapment efficiency about 95.29±1.32 % and the pH of optimized cubosomal was found to be 6.5, viscosity 2475-8901(cp), drug content 95.29% and the spreadability was found to be 11.74 gm.cm/sec. The in vitro drug release kinetics of optimized formulation was found to follow Korsmeyer peppas model having highest R2 value 0.835 and in vitro drug release of optimized erythromycin loaded cubosomal gel and plain drug gel in 24 hr was found to be 89.91±0.73 and 88.64±2.16, while in 36 hr plain drug gel and cubosomal gel showed drug release about 87.64±0.97 and 91.55±1.09, and sustained release was obtained after 24 hr in case of cubosomal gel. CONCLUSION: Thus, as a whole it can be concluded that erythromycin loaded cubosomes are effective in topically delivering drug in sustained and non-invasive manner for treatment and prevention of acne.

Feather hydrolysate from Streptomyces sampsonii GS 1322: A potential low cost soil amendment.

Process parameters for obtaining hydrolysate from hen feathers, i.e., initial pH (5.0-9.0) and incubation period (1-6 day), were set and studied, using Streptomyces sampsonii GS 1322 in submerged and solid state conditions. Under submerged conditions, complete hydrolysis of feathers was observed on fifth day [initial pH 8.0, 28 ± 2°C, shaking (150 rpm)] with release of soluble protein (2985 µg ml(-1)) and amino acids (2407 µg ml(-1)). Cell free hydrolysate showed hydrolysis of casein (18 mm), gelatin (26 mm), collagen (31 mm), hemoglobin (23 mm) and Tween 80 (35 mm) while 445 U keratinase activity. Total soluble protein reached 5 mg ml(-1) in solid state conditions. During Pot experimentation using barren agriculture soil the effect of feather hydrolysate on wheat crop were recorded. Significant increase (p<0.01) in wheat seed germination was observed in treated soils as compared to untreated. Treatment significantly increased plant height from 30 to 60 days and 30-90 days (p<0.001). Treated soil showed an increase in total microbial count, proteolytic activity, phosphate solubilizing bacteria and ammonifying bacteria, whereas pathogenic fungi load was reduced. S. sampsonii GS 1322 can be used for bio-processing of poultry wastes yielding feather hydrolysate rich in proteins and amino acids for development of low-cost organic amendment to accelerate wheat crop growth in barren agricultural land.

Coated chitosan nanoparticles encapsulating caspase 3 activator for effective treatment of colorectral cancer.

Cancer is the second leading cause of death worldwide, the deaths are projected to continue rising, with an estimated 12 million deaths in 2030. The aim of the present investigation is to prepare and compare the uncoated (U-CH NP) and eudragit S 100-coated (E-U-CH NP) chitosan nanoparticles encapsulating a caspase 3 activator (UCN 01), by ionic gelation method. The prepared formulations were studied for various parameters like particles size, zeta potential, transmission electron microscopy, atomic force microscopy, in vitro release study, ex vivo study using Caco 2 colon cancer cell line, and in vivo studies. The particle size and zeta potential of developed formulation was found to be particle size of 168 ± 3.7 nm and +35.8 ± 3.7 for U-CH NP and 265 ± 4.1 nm and +22.3 ± 1.1 for E-U-CH NP. TEM and AFM images revealed that U-CH NPs were round in shape and smoother at surface as compared to E-U-CH NP which have irregular surface due to coating. The E-U-CH NP showed better in vitro release than uncoated formulation in SCF (pH 6.8) than in SGF (pH 1.2). The cytotoxicity was performed by MTT assay. U-CH NP showed enhanced cytotoxicity as compared to blank (without drug) formulation. There was an increase in caspase 3 activity of U-CH NP as compared to UCN 01 alone. E-U-CH NP showed better tumor regression ability than U-CH NP. The results of plasma profile and tumor regression study demonstrated that E-U-CH NP has continuous release profile of UCN 01 and comprehensive residence time. Thus, it is better acceptable than free UCN 01 and may be a potential delivery system for the targeting and treatment of colon cancer.

Treatment of cutaneous candidiasis through fluconazole encapsulated cubosomes.

Cubosomes encapsulating fluconazole were prepared by emulsification method and characterized for particle size, entrapment efficiency, SEM, in vitro release, skin irritation studies, and confocal laser scanning microscopy. The cubosomes prepared were 257.2 ± 2.94 nm in size and with drug entrapment efficiency of 66.2 ± 2.69 %. The prepared formulation was characterized for surface morphology by SEM analysis which revealed their smooth surface. The cumulative percentage of fluconazole from cubosomes permeated via dialysis membrane (molecular weight cutoff (MWCO) 12-14 kD) showed 76.86 % cumulative drug release, while fluconazole solution showed release up to 91.04 % in 24 h in phosphate-buffered saline (PBS) (pH 6.5), and sustained release is obtained after 24 h in case of cubosomes. The animal studies also revealed that the cubosomes are non-irritant and have sustained antifungal activity.