Exosomes isolated from citrus lemon: a promising candidate for the treatment of Alzheimer's disease.

Aim: To investigate the efficacy of exosome-like nanovesicles from citrus lemon (EXO-CLs) in combating oxidative stress associated with Alzheimer's disease. Materials & methods: EXO-CLs were isolated through differential ultracentrifugation, characterized for particle size and evaluated for antioxidant activity. Results: EXO-CLs exhibited a mean size of 93.77 ± 12.31 nm, demonstrated permeability across the blood-brain barrier (BBB) and displayed antioxidant activity comparable to ascorbic acid. Additionally, they were found to be non-toxic, with over 80% cell viability observed in SH-SY5Y cells. Conclusion: The study proposes that EXO-CLs could serve as an effective treatment for neurodegenerative diseases. This suggests a promising approach for targeted interventions in brain-related disorders, owing to the antioxidant properties and BBB permeability exhibited by EXO-CLs.

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Novel therapeutic approaches for the management of hepatitis infections.

Hepatitis B virus (HBV) & hepatitis C virus (HCV) infection is a substantial reason for morbidity and mortality around the world. Chronic hepatitis B (CHB) infection is connected with an enhanced risk of liver cirrhosis, liver decompensation and hepatocellular carcinoma (HCC). Conventional therapy do face certain challenges, for example, poor tolerability and the growth of active resistance. Thus, novel treatment procedures are essential to accomplish the initiation of strong and stable antiviral immune reactions of the individuals. This review explores the current nanotechnology-based carriers for drug and vaccine delivery to treat HBV and HCV.

Hepatitis infections are a major health problem that affects lots of people across the globe. Without treatment, it can seriously harm the liver and might even lead to a type of liver cancer. The treatments we currently have can sometimes cause side effects or the virus can learn how to fight back against them. This means we need new and better ways to treat it. In our article, we talk about how Hepatitis B and C affects the body and how our natural defenses try to protect us. We then dive into a kind of science called nanotechnology, which uses tiny particles to help deliver medicine or vaccines in a better way. This new method could help medications be better at treating Hepatitis B and C.

Nano Lipid Carriers as a Promising Drug Delivery Carrier for Neurodegenerative Disorders - An Overview of Recent Advances.

The last few decades have seen a rise in the number of deaths caused by neurological disorders. The blood-brain barrier (BBB), which is very complex and has multiple mechanisms, makes drug delivery to the brain challenging for many scientists. Lipid nanoparticles (LNPs) such as nanoemulsions, solid-lipid nanoparticles, liposomes, and nano lipid carriers (NLCs) exhibit enhanced bioavailability and flexibility among these nanocarriers. NLCs are found to be very effective. In the last few decades, they have been a center of attraction for controlled drug delivery. According to the current global status of specific neurological disorders, out of all LNPs, NLC significantly reduces the cross-permeability of drugs through the BBB due to their peculiar properties. They offer a host of advantages over other carriers because of their biocompatibility, safety, non-toxicity, non-irritating behavior, stability, high encapsulation efficiency, high drug loading, high drug targeting, control of drug release, and ease in manufacturing. The biocompatible lipid matrix is ideally suited as a drug carrier system due to the nano-size range. For certain neurological conditions such as Parkinsonism, Alzheimer's, Epilepsy, Multiple sclerosis, and Brain cancer, we examined recent advances in NLCs to improve brain targeting of bioactive with special attention to formulation aspects and pharmacokinetic characteristics. This article also provides a brief overview of a critical approach for brain targeting, i.e., direct nose-to-brain drug delivery and some recent patents published on NLC".

Brain tuberculoma: a 52-year-old woman case report.

Introduction: One of the most serious extrapulmonary type of tuberculosis that affects people under the age of 40 is brain tuberculoma. They are space-occupying masses of granulomatous tissue that result from hematogenous spread from a distant focus of tuberculous infection by Mycobacterium tuberculosis . Symptoms and radiologic features being nonspecific usually leads to misdiagnosis and mimics a variety of other infectious diseases. Anti-tubercular drugs are essential for the successful treatment of cerebral tuberculomas. Case Report: The authors present a case report of a 52-year-old diabetic woman, who presented to the Emergency Department of a tertiary care hospital and was diagnosed with brain tuberculomas with a brain biopsy. Brain tuberculomas are rare and could be overlooked. Therefore, this is an important consideration in cases with higher suspicions, given the rapid decline in patient condition. Conclusion: Due to their rarity, ambiguous symptoms, and radiographic characteristics, intracranial tuberculomas continue to provide a clinical challenge and must always be considered in the differential diagnosis of cerebral space occupying lesions. As CSF may not yield positivity for both CBNAAT and smear examination, a brain biopsy specimen for culture should always be kept in mind for detecting tuberculoma and initiating anti-tubercular treatment at the earliest.

Propranolol HCL-loaded liposomes for intranasal delivery: in vitro and ex vivo evaluation of optimized formulation using design of experiments.

Aim: To develop a propranolol HCL-loaded liposomal nasal formulation for migraine prophylaxis. Materials & methods: Formulated the liposomes through thin layer hydration method and optimized via design of experiments (DOE). The prepared liposomes were characterized for particle size, zeta potential, PDI, drug entrapment and drug loading. Assessed for in vitro release kinetics, ex vivo permeability, histopathology and stability. Results: Optimized liposomes: 135.52 ± 5.87 nm, -19.9 ± 0.075 mV, 95.41 ± 0.05% entrapment, 43.37 ± 0.02% loading. Showed immediate (30.07 ± 2.09%) and sustained release (95.69 ± 4.58%) over 10 h. Enhanced permeation compared with controls; well-tolerated histopathologically. Conclusion: Liposomal formulation offers promise for intranasal propranolol HCL delivery in migraine prophylaxis, with stability under refrigeration.

Migraines (a type of long-lasting headache) can be helped by a medicine called propranolol HCL. In this study, scientists developed tiny bubbles, called liposomes, which contained propranolol HCL. The liposomes are designed to be inhaled via the nose, where the medicine is released slowly from the liposomes to treat the migraine. In this study, the researchers made the propranolol HCL-containing liposomes and analyzed them in the lab. They found that the liposomes were safe, and can be kept in a cool place for a long time. So, may be able to help treat migraines.

Vitreoretinal disease: a critical review on current technological perspectives and innovative drug-delivery strategies.

Aim: To review the state of the art aspects and contemporary innovative drug delivery strategies, for the treatment of vitreoretinal diseases, their mechanism of action through ocular routes and their future perspectives. Materials & methods: Scientific databases such as PubMed, Science Direct, Google scholar were used to obtain 156 papers for review. The keywords searched were vitreoretinal diseases; ocular barriers; intravitreal injections; nanotechnology; biopharmaceuticals. Results & conclusion: The review explored the various routes which can be used to facilitate drug delivery adopting novel strategies, the pharmacokinetic aspects of novel drug-delivery strategies in treating posterior segment eye diseases and current research. Therefore, this review drives focus into the same and underlines their implications to the healthcare sector in making necessary interventions.

Eye diseases that affect the major part of the eye can create eyesight loss in patients. Even though medicines are now available, there is a need to drive the existing techniques further. These can be done by the use of small sized particles in the treatment, which are easy to reach the site wherever healing is required. Natural medicines and treatment can also benefit people. In this paper, we discuss treatment approaches on these factors and their importance in curing people with eye diseases.

Nanomaterials: an intra-periodontal pocket drug-delivery system for periodontitis.

Periodontitis is a microbiological condition that affects the tissues supporting the teeth. The fundamental to effective periodontal therapy is choosing the suitable antimicrobial and anti-inflammatory agent, together with the proper route of drug administration and delivery system. Intra-periodontal pocket approach with nano drug-delivery systems (NDDS) such as polymeric nanoparticles, gold nanoparticles, silica nanoparticles, magnetic nanoparticles, liposomes, polymersomes, exosomes, nano micelles, niosome, solid lipid nanoparticles, nano lipid carriers, nanocomposites, nanogels, nanofibers, scaffolds, dendrimers, quantum dots, etc., will be appropriate route of drug administration and delivery system. This NDDS delivers the drugs at the site of infection to inhibit growth and promote tissue regeneration. The present review focused on providing comprehensive information on the NDDS for periodontitis, which enhanced therapeutic outcomes via intra-periodontal pocket delivery.

Periodontitis is a problem that can make your teeth fall out. It happens when the tissues that hold your teeth start to break down. Scientists have found a way to help treat it by using tiny things called 'nano drug-delivery systems' or NDDS. These NDDS carry medicine to the infected area and stop the germs from growing. They can also help the tissue around your teeth to heal. Some examples of NDDS are liposomes, polymersomes, exosomes, nanomicelles, and more. Regular treatment with antibiotics may not work as well as NDDS. Using NDDS can make a big difference in how well your teeth and gums heal. In the future, scientists hope to use NDDS to prevent the problem from coming back. This new way of treating periodontitis could be a big help for people with this problem.

Current trends and future perspectives for enhanced drug delivery to central nervous system in treatment of stroke.

Stroke, one of the leading causes of death around the globe, is expected to rise considerably by 2050. The expanding nanotechnology science offers a promising future for medical research treating stroke. Nanomaterials are expanding their application in stroke management by structure and function as in perfluorocarbon, iron oxide nanoparticles, gold nanoparticles, dendrimers, quantum dots, nanospheres, and other organic and inorganic nanostructures. Nanotechnology integrated with stem-cell therapy is a different hit in stroke treatment. Nonetheless, some challenges must be resolved before globalizing the use of nanomaterials in stroke treatment and other neurological disorders.

A stroke is an emergency medical condition that affects the brain. Stroke is the third leading cause of death in the US and fifth in other developing countries. Taking blood-clotting medicines, helps relieve symptoms by preventing blood clots. However, they cannot treat the cause of the disease that is causing them. Therefore, using body fluids for identifying and treating strokes will give better results. In general, giving medicine to the brain is difficult, and it is a big challenge. Nanosized small molecules help to overcome this problem. This review aims to summarize how stroke is managed and how these molecules can help.

Generation of a Live-Attenuated Strain of Chikungunya Virus from an Indian Isolate for Vaccine Development.

Chikungunya virus (CHIKV) re-emergence in the last decade has resulted in explosive epidemics. Along with the classical symptoms of fever and debilitating arthralgia, there were occurrences of unusual clinical presentations such as neurovirulence and mortality. These generated a renewed global interest to develop prophylactic vaccines. Here, using the classical approach of virus attenuation, we developed an attenuated CHIKV strain (RGCB355/KL08-p75) for the purpose. Repeated passaging (75 times) of a local clinical isolate of ECSA lineage virus in U-87 MG human astrocytoma cells, an interferon-response-deficient cell line, resulted in efficient adaptation and attenuation. While experimental infection of 3-day old CHIKV-susceptible BALB/c pups with the parent strain RGCB355/KL08-p4 resulted in death of all the animals, there was 100% survival in mice infected with the attenuated p75. In adult, immunocompetent, CHIKV-non-susceptible C57BL/6 mice, inoculation with p75 induced high antibody response without any signs of disease. Both p4 and p75 strains are uniformly lethal to interferon-response-deficient AG129 mice. Passive protection studies in AG129 mice using immune serum against p75 resulted in complete survival. Whole-genome sequencing identified novel mutations that might be responsible for virus attenuation. Our results establish the usefulness of RGCB355/KL08-p75 as a strain for vaccine development against chikungunya.

Nanotechnology Approaches for Enhanced CNS Drug Delivery in the Management of Schizophrenia.

Schizophrenia is a neuropsychiatric disorder mainly affecting the central nervous system (CNS), presented with auditory and visual hallucinations, delusion and withdrawal from society. Abnormal dopamine levels mainly characterise the disease; various theories of neurotransmitters explain the pathophysiology of the disease. The current therapeutic approach deals with the systemic administration of drugs other than the enteral route, altering the neurotransmitter levels within the brain and providing symptomatic relief. Fluid biomarkers help in the early detection of the disease, which would improve the therapeutic efficacy. However, the major challenge faced in CNS drug delivery is the blood-brain barrier (BBB). Nanotherapeutic approaches may overcome these limitations, which will improve safety, efficacy, and targeted drug delivery. This review article addresses the main challenges faced in CNS drug delivery and the significance of current therapeutic strategies and nanotherapeutic approaches for a better understanding and enhanced drug delivery to the brain, which improve the quality of life of schizophrenia patients.

Preservation of Streptococcus pneumoniae quality control strains using chocolate agar blocks in glycerol at minus 70 degrees celsius.

We present a method for storage of the quality control strain of S. pneumoniae that could be used in low resource settings. Small blocks of chocolate agar with growth were placed in glycerol (60%V/V) and stored at minus 70 °C. Viability and cultural characteristics were maintained for the testing period of 10 months. The wide availability of both chocolate agar and glycerol make this a suitable alternative to other specialized formulations usually used to maintain stocks of S. pneumoniae ATCC 49619 strain required for quality control of susceptibility testing.

Development of a Novel Methotrexate-Loaded Nanoemulsion for Rheumatoid Arthritis Treatment with Site-Specific Targeting Subcutaneous Delivery.

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease that causes disability due to progressive inflammation and destruction of the tissues around the joints. Methotrexate is mainly used to prevent the progression of joint destruction and reduce the deformity. The major challenge in treating RA with methotrexate is the systemic side effects that limit dose escalation. Hence, a novel formulation of a methotrexate-loaded nanoemulsion for subcutaneous administration was developed that aims to deliver methotrexate into the system via the lymph. The methotrexate-loaded nanoemulsion was prepared by using the aqueous-titration method. The prepared nanoemulsion was investigated for particle size, surface charge, surface morphology, entrapment efficiency, DSC (differential scanning colorimetry), drug release, hemocompatibility assay, and cytotoxicity, as well as anti-arthritic and stability studies. The vesicle size, zeta potential, PDI (polydispersity index), and entrapment efficiency of the optimized nanoemulsion were 87.89 ± 2.86 nm, 35.9 ± 0.73 mV, 0.27, and 87 ± 0.25%, respectively. The DSC study showed that the crystalline methotrexate was converted to an amorphous form and the drug was fully incorporated into the vesicles. After 72 h, the optimized nanoemulsion showed a drug release of 96.77 ± 0.63%, indicating a sustained-release dosage form. Cytocompatibility testing by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay on macrophage cell lines showed that the nanoemulsion was non-toxic. The formulation showed significant anti-arthritic activity compared to the marketed drug solution. In addition, the nanoemulsion containing methotrexate remained stable for three months when stored at a low temperature. Since the nanoemulsion containing methotrexate has excellent physicochemical properties and lowers systemic side effects by targeted delivery, it is a desirable technology for subcutaneous drug delivery.

Renal Salt-Wasting Syndrome Induced by Neoadjuvant Chemotherapy Containing Cisplatin - A Case Report.

Hyponatremia is one of the most common electrolyte abnormality seen in oncology practice. The underlying pathogenetic mechanism for chemotherapy-induced hyponatremia is renal salt-wasting syndrome (RSWS) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction is the treatment of choice in SIADH, whereas salt supplements is the mode of treatment in RSWS. Hence, differentiation between RSWS and SIADH is very important though difficult. Case reports of cisplatin (cis-dichloro-diammine-platinum-2)-induced RSWS and SIADH are rare in the literature. We report about a patient who developed hyponatremia, hypokalemia with excessive urinary excretion of sodium and potassium, renal glycosuria, and aminoaciduria on the third day of the first cycle of cisplatin-containing chemotherapy.

Isoniazid resistance in patients with Extrapulmonary Tuberculosis using line probe assay in a private multispecialty hospital in Bangalore, India.

We aimed to study the rate of isoniazid (INH) resistance in Extrapulmonary Tuberculosis samples from a private care setting. A Line probe assay was performed on 74 culture isolates of Mycobacterium tuberculosis or directly on extrapulmonary samples received in our laboratory from 2018 to 2021. The INH mono-resistance among these extrapulmonary samples was 6.7%. (5 among 74) (95% CI: 1.04%-12.48%) Resistance to rifampicin was not detected. Increasing the availability and leveraging public private partnerships in hospitals for universal testing for INH resistance may increase detection of INH monoresistance in EP-TB and improve the strategy for TB elimination.

Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies.

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50-100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.

Naturally occurring and tumor-associated variants of RNF167 promote lysosomal exocytosis and plasma membrane resealing.

Lysosomal exocytosis and resealing of damaged plasma membrane are essential for cellular homeostasis and tumor invasion. However, very little is known of the molecular machinery that regulates these physiological processes. Moreover, no mutations in any of the known regulators of lysosomal exocytosis in primary tumors of patients have been characterized. Here we demonstrate that RNF167-a, a lysosomal-associated ubiquitin ligase, negatively regulates lysosomal exocytosis by inducing perinuclear clustering of lysosomes. Importantly, we also characterized a set of novel natural mutations in RNF167-a, which are commonly found in diverse tumor types. We found that RNF167-a-K97N mutant, unlike the wild type, localizes in the cytoplasm and does not promote perinuclear lysosomal clustering. Furthermore, cells expressing RNF167-a-K97N exhibit dispersed lysosomes, increased exocytosis and enhanced plasma membrane repair. Interestingly, these functional features of RNF167-a-K97N were shared with a naturally occurring short version of RNF167 (isoform RNF167-b). In brief, the results presented here reveal a novel role of RNF167-a, as well as its natural variants RNF167-a-K97N and RNF167-b, as an upstream regulator of lysosomal exocytosis and plasma membrane resealing.

Stimuli-Responsive Polymeric Nanosystem for Colon Specific Drug Delivery.

An ideal colon specific drug delivery system needs to perform multiple functions like greater bio availability, less toxicity and higher therapeutic efficacy, all of which require high degree of smartness. This article focuses on the overview of the stimuli-responsive polymers and various nanodrug delivery systems which have found applications in colon specific delivery of drugs as this system provide a link between therapeutic need and drug delivery. These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties. Stimuli responsive polymers display a significant physio chemical change in response to small changes in their environment (temperature, pH, light etc.). Colonic drug delivery has gained increased importance in treating diseases like Crohn's disease, ulcerative colitis, colon cancer etc. The expansion in the development of polymers based system with greater flexibility, versatility and unexplored potential enables new opportunities for them in uplifting bio medicine. Applying the concepts of smartness in the context of clinically relevant therapeutic and diagnostic systems, it can prelude in a new era of 'smart' therapeutics that can improve the health care fields. In particular, due to its high sensitivity to the stimuli, this system has been identified as a sensible platform for releasing drug at suitable site and at appropriate time.

The ubiquitin ligase FBXW7 targets the centriolar assembly protein HsSAS-6 for degradation and thereby regulates centriole duplication.

Formation of a single new centriole from a pre-existing centriole is strictly controlled to maintain correct centrosome number and spindle polarity in cells. However, the mechanisms that govern this process are incompletely understood. Here, using several human cell lines, immunofluorescence and structured illumination microscopy methods, and ubiquitination assays, we show that the E3 ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7), a subunit of the SCF ubiquitin ligase, down-regulates spindle assembly 6 homolog (HsSAS-6), a key protein required for procentriole cartwheel assembly, and thereby regulates centriole duplication. We found that FBXW7 abrogation stabilizes HsSAS-6 and increases its recruitment to the mother centriole at multiple sites, leading to supernumerary centrioles. Ultrastructural analyses revealed that FBXW7 is broadly localized on the mother centriole and that its presence is reduced at the site where the HsSAS-6-containing procentriole is formed. This observation suggested that FBXW7 restricts procentriole assembly to a specific site to generate a single new centriole. In contrast, during HsSAS-6 overexpression, FBXW7 strongly associated with HsSAS-6 at the centriole. We also found that SCFFBXW7 interacts with HsSAS-6 and targets it for ubiquitin-mediated degradation. Further, we identified putative phosphodegron sites in HsSAS-6, whose substitutions rendered it insensitive to FBXW7-mediated degradation and control of centriole number. In summary, SCFFBXW7 targets HsSAS-6 for degradation and thereby controls centriole biogenesis by restraining HsSAS-6 recruitment to the mother centriole, a molecular mechanism that controls supernumerary centrioles/centrosomes and the maintenance of bipolar spindles.

UV stabilization of wood by nano metal oxides dispersed in propylene glycol.

Nanoparticles of some of the metal oxides are known to have high UV protective efficiency. The UV filtering efficiency of nanoparticles invariably depends on their size and stability in the dispersion. In the present work, a stable dispersion of nanoparticles of three metal oxides, zinc oxide (ZnO), cerium oxide (CeO2) and titanium dioxide (TiO2), was prepared in propylene glycol (PG) using ultrasonication. The method is easy and useful as no additional surfactant or dispersant is needed. The particle size and its distribution was confirmed by Scanning Electron Microscopy and Dynamic Light Scattering. The stability of dispersion was assessed by UV-visible absorption spectroscopy. The UV stability of wood surfaces of Wrightia tinctoria coated with nanodispersions of ZnO, CeO2 and TiO2 was evaluated under laboratory conditions in an accelerated weathering tester. Changes in the colour and FTIR spectra of exposed specimens were measured periodically. Rapid colour darkening (yellowing) was observed in uncoated and PG coated specimens. In contrast, nanodispersion coated specimens prevented photo-yellowing considerably with significant reduction in colour changes examined by CIE L*, a*, b* and ΔE*. Increase in concentration of nanoparticles in the dispersion imparted higher resistance to UV induced degradation. However, increased concentration of nanoparticles reduced the transparency of the coating. FTIR analysis indicated rapid degradation of lignin in uncoated and PG coated specimens due to UV exposure. Coating of wood surfaces with nanodispersions restricted lignin degradation. The study also demonstrates the potential of propylene glycol as a dispersant for developing stable and efficient UV protective nanodispersions for wood coating.