A nanoemulsified formulation of dolutegravir and epigallocatechin gallate inhibits HIV-1 replication in cellular models.

Nanotechnology offers promising avenues for enhancing drug delivery systems, particularly in HIV-1 treatment. This study investigates a nanoemulsified formulation combining epigallocatechin gallate (EGCG) with dolutegravir (DTG) for managing HIV-1 infection. The combinatorial interaction between EGCG and DTG was explored through cellular, enzymatic, and molecular studies. In vitro assays demonstrated the potential of a dual drug-loaded nanoemulsion, NE-DTG-EGCG, in inhibiting HIV-1 replication, with EGCG serving as a supplementary treatment containing DTG. In silico molecular interaction studies highlighted EGCG's multifaceted inhibitory potential against HIV-1 integrase and reverse transcriptase enzymes. Further investigations are needed to validate the formulation's efficacy across diverse contexts. Overall, by integrating nanotechnology into drug delivery systems, this study represents a significant advancement in managing HIV-1 infection.

Targeting brain tumors with innovative nanocarriers: bridging the gap through the blood-brain barrier.

Background: Glioblastoma multiforme (GBM) is recognized as the most lethal and most highly invasive tumor. The high likelihood of treatment failure arises from the presence of the blood-brain barrier (BBB) and stem cells around GBM, which avert the entry of chemotherapeutic drugs into the tumor mass. Objective: Recently, several researchers have designed novel nanocarrier systems like liposomes, dendrimers, metallic nanoparticles, nanodiamonds, and nanorobot approaches, allowing drugs to infiltrate the BBB more efficiently, opening up innovative avenues to prevail over therapy problems and radiation therapy. Methods: Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases, for example, PubMed, Science Direct, Google Scholar, and others, using specific keyword combinations, including "glioblastoma," "brain tumor," "nanocarriers," and several others. Conclusion: This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management. Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies.

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.

Potential of Nanocarrier-Associated Approaches for Better Therapeutic Intervention in the Management of Glioblastoma.

Glioblastoma, commonly known as glioblastoma multiforme (GBM), is one of the deadliest and most invasive types of brain cancer. Two factors account for the majority of the treatment limitations for GBM. First, the presence of the blood-brain barrier (BBB) renders malignancy treatment ineffective, leading to recurrence without full recovery. Second, several adverse effects are associated with the drugs used in conventional GBM treatment. Recent studies have developed nanocarrier systems, such as liposomes, polymeric micelles, dendrimers, nanosuspensions, nanoemulsions, nanostructured lipid carriers, solid lipid nanocarriers, metal particles, and silica nanoparticles, which allow drug-loaded formulations to penetrate the BBB more effectively. This has opened up new possibilities for overcoming therapy issues. Extensive and methodical searches of databases such as PubMed, Science Direct, Google Scholar, and others were conducted to gather relevant literature for this work, using precise keyword combinations such as "GBM," "brain tumor," and "nanocarriers." This review provides deep insights into the administration of drugs using nanocarriers for the management of GBM and explores new advancements in nanotechnology. It also highlights how scientific developments can be explained in connection with hopeful findings about the potential of nanocarriers for the future successful management of GBM.

Biofabrication paradigms in corneal regeneration: bridging bioprinting techniques, natural bioinks, and stem cell therapeutics.

Corneal diseases are a major cause of vision loss worldwide. Traditional methods like corneal transplants from donors are effective but face challenges like limited donor availability and the risk of graft rejection. Therefore, new treatment methods are essential. This review examines the growing field of bioprinting and biofabrication in corneal tissue engineering. We begin by discussing various bioprinting methods such as stereolithography, inkjet, and extrusion printing, highlighting their strengths and weaknesses for eye-related uses. We also explore how biological tissues are made suitable for bioprinting through a process called decellularization, which can be achieved using chemical, physical, or biological methods. The review then looks at natural materials, known as bioinks, used in bioprinting. We focus on materials like gelatin, collagen, fibrin, chitin, chitosan, silk fibroin, and alginate, examining their mechanical and biological properties. The importance of hydrogel scaffolds, particularly those based on collagen and other materials, is also discussed in the context of repairing corneal tissue. Another key area we cover is the use of stem cells in corneal regeneration. We pay special attention to limbal epithelial stem cells and mesenchymal stromal cells, highlighting their roles in this process. The review concludes with an overview of the latest advancements in corneal tissue bioprinting, from early techniques to advanced methods of delivering stem cells using bioengineered materials. In summary, this review presents the current state and future potential of bioprinting and biofabrication in creating functional corneal tissues, highlighting new developments and ongoing challenges with a view towards restoring vision.

Antiretroviral action of Rosemary oil-based atazanavir formulation and the role of self-nanoemulsifying drug delivery system in the management of HIV-1 infection.

Atazanavir or ATV is an FDA-approved, HIV-1 protease inhibitor that belongs to the azapeptide group. Over time, it has been observed that ATV can cause multiple adverse side effects in the form of liver diseases including elevations in serum aminotransferase, indirect hyper-bilirubinemia, and idiosyncratic acute liver injury aggravating the underlying chronic viral hepatitis. Hence, there is an incessant need to explore the safe and efficacious method of delivering ATV in a controlled manner that may reduce the proportion of its idiosyncratic reactions in patients who are on antiretroviral therapy for years. In this study, we assessed ATV formulation along with Rosemary oil to enhance the anti-HIV-1 activity and its controlled delivery through self-nanoemulsifying drug delivery system or SNEDDS to enhance its oral bioavailability. While the designing, development, and characterization of ATV-SNEDDS were addressed through various evaluation parameters and pharmacokinetic-based studies, in vitro cell-based experiments assured the safety and efficacy of the designed ATV formulation. The study discovered the potential of ATV-SNEDDS to inhibit HIV-1 infection at a lower concentration as compared to its pure counterpart. Simultaneously, we could also demonstrate the ATV and Rosemary oil providing leads for designing and developing such formulations for the management of HIV-1 infections with the alleviation in the risk of adverse reactions.

Advancing the one health approach through integration of Ayush systems: Opportunities and way forward.

The Ayush systems in India, specifically Ayurveda, have a large pool of infrastructure, human resources, and unique modalities for disease prevention, wellness, and management. These systems have seen significant growth in recent years, with the budget allocation for the Ayush Ministry increasing fourfold from INR 691 crore to INR 3050 crore over the last seven years. The Ayush systems can contribute significantly to the One Health approach, which addresses the interconnectedness of human, animal, and environmental health. The current commentary explores the areas of work related to the One Health approach, the potential role of the Ayush system in addressing these existing policies that support the integration of Ayush in the One Health approach, and future perspectives on the role of Ayush in One Health. Ayush systems advocate preventive measures, such as daily and seasonal regimens and the use of rejuvenating herbs and drugs, as well as therapeutic interventions for a range of health issues. Ayurveda also addresses environmental, animal, and plant health issues and promotes the creation of a healthy ecosystem between humans, animals, and the environment. In addition, Ayush can play a role in addressing zoonotic diseases, noncommunicable diseases, antimicrobial resistance, food safety and health of the elderly, children, and environment. To fully utilize the potential of Ayush in the One Health approach, these systems should be integrated into the healthcare infrastructure and network. Furthermore, initiation of collaborative projects, focused research, training and sensitization of Ayush human resources, and promotion of Ayush-based lifestyles and practices are some of the critical steps required to be taken.

siRNA therapeutics: insights, challenges, remedies and future prospects.

INTRODUCTION: Among conventional and novel therapeutic approaches, the siRNA strategy stands out for treating disease by silencing the gene responsible for the corresponding disorder. Gene silencing is supposedly intended to target any disease-causing gene, and therefore, several attempts and investments were made to exploit siRNA gene therapy and advance it into clinical settings. Despite the remarkable beneficial prospects, the applicability of siRNA therapeutics is very challenging due to various pathophysiological barriers that hamper its target reach, which is the cytosol, and execution of gene silencing action. AREAS COVERED: The present review provides insights into the field of siRNA therapeutics, significant in vivo hurdles that mitigate the target accessibility of siRNA, and remedies to overcome these siRNA delivery challenges. Nonetheless, the current review also highlights the on-going clinical trials and the regulatory aspects of siRNA modalities. EXPERT OPINION: The siRNAs have the potential to reach previously untreated target sites and silence the concerned gene owing to their modification as polymeric or lipidic nanoparticles, conjugates, and the application of advanced drug delivery strategies. With such mounting research attempts to improve the delivery of siRNA to target tissue, we might shortly witness revolutionary therapeutic outcomes, new approvals, and clinical implications.

Nanotechnology revolutionises breast cancer treatment: harnessing lipid-based nanocarriers to combat cancer cells.

One of the most common cancers that occur in females is breast cancer. Despite the significant leaps and bounds that have been made in treatment of breast cancer, the disease remains one of the leading causes of death among women and a major public health challenge. The therapeutic efficacy of chemotherapeutics is hindered by chemoresistance and toxicity. Nano-based lipid drug delivery systems offer controlled drug release, nanometric size and site-specific targeting. Breast cancer treatment includes surgery, chemotherapy and radiotherapy. Despite this, no single method of treatment for the condition is currently effective due to cancer stem cell metastasis and chemo-resistance. Therefore, the employment of nanocarrier systems is necessary in order to target breast cancer stem cells. This article addresses breast cancer treatment options, including modern treatment procedures such as chemotherapy, etc. and some innovative therapeutic options highlighting the role of lipidic nanocarriers loaded with chemotherapeutic drugs such as nanoemulsion, solid-lipid nanoparticles, nanostructured lipid carriers and liposomes, and their investigations have demonstrated that they can limit cancer cell growth, reduce the risk of recurrence, as well as minimise post-chemotherapy metastasis. This article also explores FDA-approved lipid-based nanocarriers, commercially available formulations, and ligand-based formulations that are being considered for further research.

Monoclonal antibodies and antibody-drug conjugates as emerging therapeutics for breast cancer treatment.

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multispecific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

Designing lisuride intranasal nanocarrier system for reduction of oxidative damage with enhanced dopamine level in brain for Parkinsonism.

In the present study, nanoemulsion (NE) loaded with lisuride were formulated for delivering drug to brain via intranasal route. Dopamine levels, pharmacokinetic, and antioxidant activity were estimated. Antioxidant effect of lisuride NE was assessed in-vivo using oxidative stress models revealing symptoms like those of Parkinson's disease. Intranasally administered lisuride NE-treated group revealed a greater number of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione (GSH) as compared to the intravenously administered lisuride suspension in haloperidol rat model. Additionally, it was observed that lisuride NE can decrease dopamine loss. When lisuride NE was administered intranasally resulted in considerably higher dopamine concentrations (17.48 ± 0.05 ng/mL) in comparison to rats receiving haloperidol (7.28 ± 0.02 ng/mL). From study, it is suggested that NE is a possible strategy to deliver lisuride intranasally to lower free radical damage and prevent the biochemical alterations associated with Parkinson's disease.

Cardiac synovial sarcoma masquerading as effusive constrictive pericarditis.

Primary cardiac synovial sarcoma is a rare entity, arising from the pericardium or the chambers of the heart. It presents in the 4th decade of life with a striking male predisposition. We describe an unusual case of a 22-year-old female who presented with complaints of dyspnoea on exertion, palpitations, and chest pain. Trans-thoracic echocardiography was suggestive of a cystic pericardial mass with pericardial effusion anterior and lateral to the right ventricle. Computed tomography scan (CT scan) revealed thick-walled predominantly cystic lesion over the left ventricle with gross pericardial effusion with internal septations. These findings were suggestive of an infected pericardial cyst. Upon surgery, an adherent mass in the pericardial cavity was found which was not separable from the right heart structures, the great vessels, and the left ventricle. Biopsy was taken, histopathology was suggestive of spindle cell neoplasm, and an immunohistochemistry analysis revealed Transducin-like enhancer of split 1 (TLE 1)-positive malignant spindle cell tumour likely synovial sarcoma. After surgery, the patient received serial adjuvant chemo-radiation therapy. The synovial sarcoma masqueraded as effusive constrictive pericarditis, due to which it eluded preoperative diagnosis.

Mechanistic Role of Methanolic Extract of Taraxacum officinale Roots as Cardioprotective Against Ischemia-Reperfusion Injury-Induced Myocardial Infarction in Rats.

Taraxacum officinale play an important role in the prophylaxis and treatment of cardiovascular disease (CVD). Taraxacum officinale is proven as promising antioxidant in earlier studies and one of its constituent "cichoric acid" is shown to have vasorelaxant property. Therefore, present study mainly designed to investigate the cardioprotective effects of Taraxacum officinale against ischemia-reperfusion injury (I/R injury)-induced myocardial dysfunction in rats. This study not only explored the overall cardioprotective potential but also tried to explore its molecular mechanism using pharmacological inhibition via L-NAME and glibenclamide. Pretreatment of methanolic extract of Taraxacum officinale significantly attenuated (p < 0.001) increased levels of lactate dehydrogenase (LDH), creatine kinase (CK), infarct size, and thiobarbituric acid reactive substance (TBARS), while it increased the reduced levels of protein content, glutathione (GSH), and catalase (CAT) activity. Results showed that pretreatment with methanolic extract of Taraxacum officinale provides cardioprotection against I/R induced myocardial dysfunction, at least, may be mediated through the endogenous release of nitric oxide.

Closing human resources gap in health: Moving beyond production to proactive recruitments.

Human Resources for Health (HRH) plays an integral role in healthcare service delivery. Gap in HRH has been a major concern with our healthcare ecosystem for a long time. It is vital to have adequately staffed public healthcare facilities, which are freely accessible to the population. To understand the reasons, we looked at the production, availability, and vacancies of HRH existing in public sector as well as measures taken for closing HRH gap during the period 2014-2015 to 2019-2020 and best practices adopted by the some of the State/UTs. We relied on official websites and official reports/statistics. While teaching capacity has increased significantly in recent past, and there are sufficient numbers of registered HRH, it has not translated into the recruitment of HRH in public facilities. Measures like campus placement, assured career progression, efficient and transparent recruitment process, modern and responsive HR management system, financial and non-financial incentives and notification of the vacant posts can play a vital role in filling the existing gaps. Some of the states have taken proactive measures for filling the vacancies, which can be replicated. The vacancies need to be filled in a mission mode. States also need to sanction required posts as per the norms. The ratio between different categories of healhtcare staff should be taken into consideration while sanctioning posts for these cadres. Availability of HRH in public sector as per norms would contribute toward achieving Sustainable Development Goal-3, reducing out of pocket expenditure and bring enormous socioeconomic gains.

Mechanistic Insights into the Pharmacological Significance of Silymarin.

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, ß-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

WITHDRAWN: Pharmaceutical Nanoemulsion System: A Strategy to Enhance the Bioavailability of Drugs

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Role of nitazoxanide as a repurposed drug in the treatment and management of various diseases.

Nitazoxanide (NTZ) is an orally active drug with significant postmarketing experience including more than 75 million adults and children. Presently, this drug is widely used for a number of infectious conditions and diseases. It has a wide range of applications such as antiprotozoal, anthelmintic and antiviral against various types of Gram-positive and Gram-negative bacteria, parasites and certain viruses. Chemically, NTZ nitrothiazole is a [2-[(5-nitro-1,3- thiazol-2-yl) carbamoyl]phenyl] acetate compound. A number of clinical trials have suggested that it can be used in cryptosporidiosis, hepatitis B, hepatitis C, ovarian cancer, viral infections and helicobacter infection. Recent research has proposed its beneficial effect in treating the symptoms of coronavirus infection. It is proposed that the activity of NTZ is due to interference with pyruvate-ferredoxin oxidoreductase (PFOR), which is an enzyme that catalyzes the ferredoxin-dependent electron transfer reaction completed in anaerobiotic energy metabolism. The available literature suggested the importance of NTZ and its efficiency against various bacterial infections as well as in viral infectious diseases. The aim of this review is to examine and discuss the most important aspects of NTZ in different types of microbial infections.

CCRD based development of bromocriptine and glutathione nanoemulsion tailored ultrasonically for the combined anti-parkinson effect.

Bromocriptine Mesylate (BRM) acts as a dopamine receptor agonist along with antioxidant effect and is utilized in the treatment of Parkinson's disease (PD). Glutathione (GSH) is a thiol- reducing agent having antioxidant properties in the brain. Replenishment of GSH inside the brain can play a major role in the management of PD. Both BRM and GSH suffer from low oral bioavailability and poor absorption. The objective of the present study was to develop BRM and GSH loaded nanoemulsion for the combined and synergistic effect delivered through the intranasal route for the better and effective management of PD. After extensive screening experiments, Capmul PG-8 NF was selected as oil, polyethylene glycol (PEG) 400 as a surfactant and propylene glycol as co-surfactant. Ultrasonication technique was employed for the fabrication of nanoemulsion. Central composite rotatable design (CCRD) was used to obtain the best formulation by optimization. Oil (%), Smix (%), and sonication time (second) were chosen as independent variables for the optimization. Particle size, PDI, zeta potential, % transmittance, pH, refractive index, viscosity and conductivity of the optimized nanoemulsion were found to be 80.71 ± 2.75 nm, 0.217 ± 0.009, -12.60 ± 0.10 mV, 96.00 ± 3.05 %, 6.48 ± 0.28, 1.36 ± 0.03, 30.12 ± 0.10 mPas and 214.28 ± 2.79 µS/cm respectively. Surface morphology demonstrated that nanoemulsion possessed spherical and globular nature of the particle which showed 3.4 times and 1.5 times enhancement in drug permeation in the case of BRM and GSH respectively as compared to suspension. MTT assay done on neuro-2a cell lines revealed that nanoemulsion was safe for intranasal delivery. Behavioural studies were carried out to prove the efficacy of optimized nanoemulsion in PD using forced swimming test, locomotor activity test, catalepsy test, rota-rod test, and akinesia test in Wistar rats. The outcomes of the behavioural studies revealed that BRM and GSH loaded nanoemulsion treatment showed significant improvement in behavioural activities of PD (haloperidol-induced) rats after intranasal administration. This study concluded that BRM and GSH loaded nanoemulsion could be promising for the combined and synergistic anti-parkinson effect for the effective management of PD.

Envisioning the Future of Nanomedicines in Management and Treatment of Neurological Disorders.

Neurodegenerative disorders are a result of continuous deterioration of the structure and function of neurons, involving the death of neurons. Neurodegenerative disorders affect millions of people around the world. Several conventional drug delivery strategies are available to treat neurological disorders. However, they are unable to provide adequate cytoarchitecture restoration and connection patterns due to lower solubility, poor bioavailability, drug resistance and incapability to traverse the blood-brain barrier (BBB). Therefore, designing and developing new and efficient delivery systems, that can bring drugs to CNS and have good bioavailability in the brain is very important. Nano drug delivery system acts as a ray of hope in the diagnosis and treatment of neurological disorders. The use of nanomedicines encapsulating therapeutic molecules may enhance transport of drug across BBB, absorption of drug and its controlled release in the human body with minimum adverse effects. This review article includes a comprehensive overview of the BBB, recent developments and application of nanomedicines, including liposomes, nanoparticles, nanomicelles, carbon nanotubes, etc., to the management as well as clinical therapy of various neurodegenerative disorders.