In-vitro and ex-vivo antidiabetic, and antioxidant activities of Box-Behnken design optimized Solanum xanthocarpum extract loaded niosomes.

One of the most prevalent lifestyle diseases, diabetes mellitus (DM) is brought on by an endocrine issue. DM is frequently accompanied by hyperglycemia, a disease that typically results in an excess of free radicals that stress tissues. The medical community is currently concentrating on creating therapeutic medications with roots in nature to lessen the damage associated with hyperglycemia. Solanum xanthocarpum has a number of medicinal benefits. The investigation aimed to produce and analyze niosomal formulations containing S. xanthocarpum extract (SXE). Niosomes were made by implementing the solvent evaporation process, which was further optimized using Box-Behnken design. Drug release, DPPH assessments, α-amylase inhibition assay, α-glucosidase inhibition assay, and confocal laser scanning microscopy (CLSM) investigation were all performed on the developed formulation (SXE-Ns-Opt). SXE-Ns-Opt displayed a 253.6 nm vesicle size, a PDI of 0.108, 62.4% entrapment efficiency, and 84.01% drug release in 24 h. The rat's intestinal CLSM image indicated that the rhodamine red B-loaded SXE-Ns-Opts had more intestinal penetration than the control. Additionally, the antioxidant effect of the obtained formulation was demonstrated as 89.46% as compared to SXE (78.10%). Additionally, acarbose, SXE, and SXE-Ns-Opt each inhibited the activity of α-amylase by 95.11%, 85.88%, and 89.87%, and also suppressed the enzyme of α-glucosidase by 88.47%, 81.07%, and 85.78%, respectively. To summarise, the establishment of the SXE-Ns-Opt formulation and its characterization demonstrated the legitimacy of the foundation. A promising candidate for the treatment of diabetes mellitus has been shown as in vitro studies, antioxidant against oxidative stress, CLSM of rat's intestine and a high degree of penetration of formulation.

Formulation and Evaluation of Plumbagin-Loaded Niosomes for an Antidiabetic Study: Optimization and In Vitro Evaluation.

Diabetes treatment requires focused administration with quality systemic circulation to determine the optimal therapeutic window. Intestinal distribution through oral administration with nanoformulation provides several benefits. Therefore, the purpose of this study is to create plumbagin enclosed within niosomes using the quality by design (QbD) strategy for efficient penetration and increased bioavailability. The formulation and optimization of plumbagin-loaded niosomes (P-Ns-Opt) involved the use of a Box-Behnken Design. The particle size (PDI) and entrapment efficiency of the optimized P-Ns-Opt were 133.6 nm, 0.150, and 75.6%, respectively. TEM, DSC, and FTIR were used to analyze the morphology and compatibility of the optimized P-Ns-Opt. Studies conducted in vitro revealed a controlled release system. P-Ns-Opt's antioxidant activity, α-amylase, and α-glucosidase were evaluated, and the results revealed a dose-dependent efficacy with 60.68 ± 0.02%,90.69 ± 2.9%, and 88.43 ± 0.89%, respectively. In summary, the created P-Ns-Opt demonstrate remarkable potential for antidiabetic activity by inhibiting oxygen radicals, α-amylase, and α-glucosidase enzymes and are, therefore, a promising drug delivery nanocarrier in the management and treatment of diabetes.

Influence of toll-like receptor-4 antagonist on bacterial load of asthma in Swiss albino mice: targeting TLR4/MD2 complex pathway.

Air pollution and environmental issues significantly impact life, resulting in the emergence and exacerbation of allergic asthma and other chronic respiratory infections. The main objective of this study is to suppress allergic asthma by TAK-242 from lipopolysaccharide-induced airway inflammation primarily stimulating toll-like receptor-4, and also to determine the potential mechanism of asthma eradication. The TAK-242 anti-allergic action was assured through the ovalbumin murine model of asthma via bronchial hyperresponsiveness and inflammation of the respiration tract in a pre-existing allergic inflammation paradigm. Swiss albino mice were sensitized and then challenged by ovalbumin and lipopolysaccharide for 5 days straight. TAK-242 reaction was assessed by inflammatory cytokines, and inflammatory cell count was determined from blood serum and bronchoalveolar lavage fluid, as well as group-wise regular weight assessments. After ovalbumin, lipopolysaccharide infusion, toll-like receptor-4 agonists caused a substantial increase in airway hyperresponsiveness, specific cellular inflammation, histological alterations, and immune mediator synthesis, as well as dose-related body-weight variations. A decrease in lipopolysaccharide-induced leukocyte count and Th1/Th17 related cytokines, TNF-α, and IL-6 expression through the ELISA study was particularly noticeable. Finally in treated groups, TAK-242, a TLR4/MD2 complex inhibitor, reduced airway inflammation and histopathological changes, cytokine expression, and body-weight management. TAK-242 has been found in an ovalbumin allergic asthma model to be a potential inhibitor of lipopolysaccharide-induced respiratory infection.

Focusing the pivotal role of nanotechnology in Huntington's disease: an insight into the recent advancements.

Neurodegeneration is the loss of neuronal capacity and structure over time which causes neurodegenerative disorders like Alzheimer, amyotrophic lateral sclerosis, Parkinson, and Huntington's disease (HD). This review is primarily concerned with HD, which was fully described by George Huntington in 1872. In developed countries, HD has become another common single-gene neurological disorder. Because of its autosomal dominant inheritance, the sickness affects both individuals and their families. Huntington disease has been recognized as a disorder that affects the complete body and brain in which the mutant huntingtin polyglutamine (polyQ) sequence is extensively increased and gets correlated to CAG trinucleotide which codes for glutamine (Q). These proteins have characteristics that produce apoptosis and dysfunction. HD is a lethal condition which needs an immediate diagnosis and treatment, and therefore, nanoparticle has come into sight out as opportunistic strategies for treatment of HD. Nanostructures have great potential to cross the blood brain barrier and also prevent breakdown of active molecule and reduces the drug toxicity. This review explains the distinguishing symptoms, genetics, and stages during the development of Huntington's disease, and also provides an overview of HD with an emphasis on its epidemiology, pathogenesis, and management. This review focuses on the latest studies on nanotechnology-related technologies, i.e., magnetic nanoparticle, solid lipid nanoparticle, and polymeric nanoparticle for Huntington's disease treatment. The pioneering patents and in-progress clinical trials related to Huntington's disease has also been summarized in this review.

Circumstantial Insights into the Potential of Traditional Chinese Medicinal Plants as a Therapeutic Approach in Rheumatoid Arthritis.

The advanced era has invited a plethora of chronic and autoimmune infirmities unmistakably dominated by rheumatoid arthritis, occurring because of equivocal causes, including ecological factors, genetic variations, etc. Unfortunately, it is winning pretty much in every stratum of the society in the undefined age group of the population. Engineered drugs are accessible for the treatment; however, they do experience adverse effects as the treatment requires a prolonged duration worsened by noncompliance. To overwhelm it, certain pharmacological and molecular pathways are explored in the wake of Chinese herbs that prompted the prevention of this deteriorating autoimmune disease. The alcoholic extracts and decoctions are procured from Chinese herbs, such as Paeonia lactiflora, Glycyrrhiza uralensis, Tripterygium wilfordii, etc., which have been proved to manifest constructive pharmacological actions. The activities that were exhibited by extracts are significantly innocuous, non-toxic, and potent to fix the affliction in contrast with the chemosynthetic drugs. Therefore, these Chinese herbs bring forth potent anti-inflammatory, immune-suppressing, anti-nociceptive, anti-neovascularizing, free radical scavenging activities, and various other benefits to withstand several pathological events that usually endure infirmity. It can be abridged that Chinese herbs possess assorted and selective therapeutic properties with profound safety and viability to treat this rheumatic disorder. Thus, this review aims to shed light on naturally originated treatment that is pertinent to providing invulnerable therapy exonerating from adverse effects by restraining joint deformities, production of auto-antibodies, and inflammation.

Targeting therapeutic approaches and highlighting the potential role of nanotechnology in atopic dermatitis.

Atopic dermatitis is a chronic as well as widespread skin disease which has significant influence on the life attributes of affected people and their families. Systemic immunosuppressive drugs can be utilised for effective care of disease, although they are often prescribed for rigorous disruption or disease that is complicated to manage. Therefore, topical applications of corticosteroids are considered the primary pharmacologic therapies for atopic dermatitis, and research recommends that these medications might be helpful in preventing disease flare-ups. However, topical medicine administration to deeper layers of skin is challenging because of the skin anatomic barrier that restricts deeper drug permeation, and also due to barrier function abnormalities in atopic dermatitis skin, which might result in systemic drug absorption, provoking systemic consequences. Hence, effective management of atopic dermatitis needs new, effective, safe and targeted treatments. Therefore, nanotechnology-based topical therapeutics have attracted much interest nowadays because of their tendency to increase drug diffusion and bioavailability along with enormous drug targeting potential to affected cells, and, thereby, reducing the adverse effects of medications. In this review, we mention different symptoms of atopic dermatitis, and provide an overview of the different triggering factors causing atopic dermatitis, with emphasis on its epidemiology, pathophysiology, clinical features and diagnostic, and preventive measures. This review discusses existing therapeutics for treating atopic dermatitis, and the newer approaches as well as the current classical pharmacotherapy of atopic dermatitis against new nanoparticle skin delivery systems. This review has also briefly summarised the recent patents and clinical status of therapeutic modalities for atopic dermatitis.

Emergence of microneedles as a potential therapeutics in diabetes mellitus.

Diabetes mellitus is a severe condition in which the pancreas produces inadequate insulin or the insulin generated is ineffective for utilisation by the body; as a result, insulin therapy is required for control blood sugar levels in patients having type 1 diabetes and is widely recommended in advanced type 2 diabetes patients with uncontrolled diabetes despite dual oral therapy, while subcutaneous insulin administration using hypodermic injection or pump-mediated infusion is the traditional route of insulin delivery and causes discomfort, needle phobia, reduced adherence, and risk of infection. Therefore, transdermal insulin delivery has been extensively explored as an appealing alternative to subcutaneous approaches for diabetes management which not only is non-invasive and easy, but also avoids first-pass metabolism and prevents gastrointestinal degradation. Microneedles have been commonly investigated in human subjects for transdermal insulin administration because they are minimally invasive and painless. The different types of microneedles developed for the transdermal delivery of anti-diabetic drugs are discussed in this review, including solid, dissolving, hydrogel, coated, and hollow microneedles. Numerous microneedle products have entered the market in recent years. But, before the microneedles can be effectively launched into the market, a significant amount of investigation is required to address the numerous challenges. In conclusion, the use of microneedles in the transdermal system is an area worth investigating because of its significant benefits over the oral route in the delivery of anti-diabetic medications and biosensing of blood sugar levels to assure improved clinical outcomes in diabetes management.

Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies.

Meningitis is an inflammation of the protective membranes called meninges and fluid adjacent the brain and spinal cord. The inflammatory progression expands all through subarachnoid space of the brain and spinal cord and occupies the ventricles. The pathogens like bacteria, fungi, viruses, or parasites are main sources of infection causing meningitis. Bacterial meningitis is a life-threatening health problem that which needs instantaneous apprehension and treatment. Nesseria meningitidis, Streptococcus pneumoniae, and Haemophilus flu are major widespread factors causing bacterial meningitis. The conventional drug delivery approaches encounter difficulty in crossing this blood-brain barrier (BBB) and therefore are insufficient to elicit the desired pharmacological effect as required for treatment of meningitis. Therefore, application of nanoparticle-based drug delivery systems has become imperative for successful dealing with this deadly disease. The nanoparticles have ability to across BBB via four important transport mechanisms, i.e., paracellular transport, transcellular (transcytosis), endocytosis (adsorptive transcytosis), and receptor-mediated transcytosis. In this review, we reminisce distinctive symptoms of meningitis, and provide an overview of various types of bacterial meningitis, with a focus on its epidemiology, pathogenesis, and pathophysiology. This review describes conventional therapeutic approaches for treatment of meningitis and the problems encountered by them while transmitting across tight junctions of BBB. The nanotechnology approaches like functionalized polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, nanoemulsion, liposomes, transferosomes, and carbon nanotubes which have been recently evaluated for treatment or detection of bacterial meningitis have been focused. This review has also briefly summarized the recent patents and clinical status of therapeutic modalities for meningitis.

Mechanistic insights into the role of B cells in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease epitomized by severe inflammation that induces tendon, cartilage, and bone damage over time. Although different types of cells undertake pathogenic functions in RA, the B cell's significant involvement has increasingly been known following the development of rheumatoid factor and it has been re-emphasized in recent years. Therefore, the rheumatoid factors and anti-cyclic citrullinated peptide antibodies are well-known indications of infection and clinical manifestations, and that they can precede the development of illness by several years. The emergence of rituximab a B cell reducing chimeric antidote in 1997 and 1998 transformed B-cell-targeted therapy for inflammatory disorder from a research hypothesis to a functional fact. Ever since, several autoantibody-related conditions were addressed, including the more intriguing indications of effectiveness seen in rheumatoid arthritis patients. Numerous types of B-cell-targeted compounds are currently being researched. From the beginning, one of the primary goals of B-cell therapy was to reinstate some kind of immune tolerance. While B cells have long been recognized as essential autoantibody producers, certain antibody-independent functions and usefulness as a key targeted therapy were not recognized until recently. The knowledge of B cells' diverse physical and pathogenic roles in autoimmune diseases is growing. As a result, the number of successful agents targeting the B cell complex is becoming more ubiquitous. Therefore, in this article, we explore fresh perspectives upon the roles of B cells in arthritis treatment, as well as new evidence regarding the effectiveness of B lymphocytes reduction and the therapeutic outcome of biological markers.

LC and LC-MS/MS studies for identification and characterization of new degradation products of ibrutinib and elucidation of their degradation pathway.

Forced degradation/stress degradation studies of ibrutinib drug were done in hydrolytic (acidic, alkaline and neutral), thermal, photolytic and oxidative degradation conditions in different temperature conditions as per International Conference on Harmonization (ICH) guideline Q1A(R2) in order to identify and characterize degradation products (DPs) of ibrutinib. The study revealed that ibrutinib is extremely sensitive to oxidative degradation even at room temperature. The drug substance is highly sensitive to alkaline hydrolysis and susceptible to acidic hydrolysis at 80 °C temperature condition, whereas found stable in neutral, photolytic and thermal stress conditions. Successful separation of ibrutinib and its ten degradation products formed during stress degradation condition were observed using Waters Acquity UPLC C-18 stationary phase (100 mm × 2.1 mm, 1.7 µm) with gradient elution using mobile phase consisting of Eluent-A: ammonium acetate (20 mm, pH-6) and Eluent-B: acetonitrile. The detection was carried out at 215 nm wavelength. Flow rate was set at 0.3 mL/min with injection volume of 5 µL. The drug substance degraded to one degradation product (DP-I) in acidic hydrolysis, five DPs (DP-I, DP-II, DP-V, DP-VIII and DP-IX) in basic hydrolysis and five DPs (DP-III, DP-IV, DP-VI, DP-VII and DP-X) in oxidative degradation condition. A novel and highly sensitive HRMS/MS/TOF method was developed to identify and characterize all the ten DPs formed during stress study. All the DPs were characterized using ESI positive mode. Except DP-I, all the degradation products formed were found to be new degradation impurities and their fragmentation pathways have never been reported earlier. The proposed mechanism and pathway of degradation products of ibrutinib were discussed and outlined.

Perspective, perceptions, and promulgation of biosimilars: A questionnaire-based study to assess and understand the current challenges of biosimilars to the potential and intended users.

INTRODUCTION: Biosimiliar, a copy of reference biological product, is making a buzz across the globe for its upper edge therapeutic usage. According to the market research report published by P&S Intelligence, biosimilars market is expected to generate $26.7 billion revenue by 2024, advancing at a CAGR of 29.6% during the forecast period. The first biosimilar to medicine Omnitrope, was approved in Europe by EMA (European Medicines Agency) in year 2006. Till date countries like US, China, Japan, India and many more have generated regulatory guidelines for biosimilars. AIM: Current study addresses the issues and challenges faced by Industry and regulators with their potential solutions and recommendations. MATERIALS AND METHODS: The questionnaire having 21 important questions/comments was given to participants after explaining the purpose of the study. The response in terms of responders V/s non-responders, agree V/s disagree, yes V/s no was recorded and analyzed by descriptive statistics. RESULTS AND DISCUSSION: The study shows the limitation regarding the qualified personnel involved in biosimilars, as approx. 91% people believe that there is lack of expertise in this field. The same can be achieved through government initiatives for bridge courses which is also strongly felt by the major (83.6%) stakeholders participated in the study.

Terror of 10 MB, a cross-sectional study investigates the regulation to the prospective of medical device.

An instrument, apparatus, implement, machine, implant, in vitro reagent, a component part or accessory which Intended for use in diagnosis of disease or other condition, or in the cure, mitigation and treatment or prevention of disease is called medical devices. Medical devices under new rule classified as Class A (low risk), Class B (low moderate risk), Class C (moderate high risk), and Class D (high risk) commemorating the notification of January 31, 2017 of Ministry of Health and Family Welfare which is conformity with Global Harmonisation Task Force framework. As per make in India program, the industry of medical devices is USD 5.2 billion and is contributing 4%-5% to the USD 96.7 billion Indian health-care industry. A total of 750-800 medical device manufacturers in India, an average investment of Rs 170-200 million and an average turnover of Rs 450-500 million. An online licensing portal of the Central Drugs Standard Control Organization (CDSCO) called "Sugam portal" has been launched on November 14, 2015, to file application and grant permission of registration exclusively for Medical Device CDSCO MD Online portal. By making the document submission easier, there are lot of challenges also present in "Sugam-online Portal." One of the main challenges in Sugam Portal is that there is no provision to upload files greater than 10MB file size. The current study addresses the issues and challenges faced by medical device industry and regulators with their potential solutions and recommendations.

A questionnaire-based study to assess the status and perspective of fixed-dose combination among the various stakeholders including regulators, clinicians, researchers, and industry.

Fixed-dose combinations (FDCs) dominating the global market because of better compliance. However, irrational combination can lead to human-made menace in terms of development of resistance, tolerance, drug abuse, and economy encumbrance. The US Food and Drug Administration defines a combination product as "a product composed of any combination of a drug and a device or a biological product and a device or a drug and a biological product or a drug, device, and a biological product." Unfortunately, many FDC being introduced in India are usually irrational. The need for the present study arises as the Indian drug regulatory system has been oscillating between central drug authorities versus state drug regulatory authorities. To assess the same fifty-six regulators and 70 other stakeholders including researchers, clinician, and industry people have exposed to 14 questions, and the same are used to get the insights of FDC among producers and consumers. All data were analyzed using Sigma plot Software. Data was presented in the form of percentage of response (responders vs. nonresponders, agree vs. disagree, yes vs. no). Most of the stakeholders (99%) stressed on Rule 122 to be strictly followed and same should be disseminated among all the stakeholders. Similarly, it was emphasized by more than 95% stakeholders that FDC contents should be tested as per official pharmacopoeia.

In vitro antioxidant and antinociceptive properties of Porphyra vietnamensis.

BACKGROUND: Current investigation explores the anti-oxidant and antinociceptive potential of edible seaweed namely Porphyra vietnamensis. METHODS: Radical scavenging and antinociceptive potential of ethanolic (EE), aqueous (AE), acetone (ACE) and chloroform (CE) fractions were determined using various models and assays. Writhing, formalin, hot plate, acetic acid induce response models were performed to determine antinociceptive activity whereas different assays have been used to determine antioxidant potential. RESULTS: Among the various fractions, ACE showed maximum biological activity. In DPPH assay half maximal inhibitory concentration (IC50) was found to be 0.470 ug/ml (DPPH assay), 0.381 jug/m/ (H2O2 assay), 0.470 ug/ml (super oxide assay), 0.591ug/ml (lipid peroxidation) and 0.430 ug/ml (nitric oxide assay). However, comparatively the TPC was more in EE (977.0 mg GAE/gm DW). CONCLUSION: It was concluded that acetone fraction of Porphyra showed marked antinociceptive and antioxidant activities, however pharmacological and chemical investigations are required to identify principle compounds responsible for activities and characterize their respective mechanism(s) for respective actions.

Validated modified Lycopodium spore method development for standardisation of ingredients of an ayurvedic powdered formulation Shatavaryadi churna.

Validated modified lycopodium spore method has been developed for simple and rapid quantification of herbal powdered drugs. Lycopodium spore method was performed on ingredients of Shatavaryadi churna, an ayurvedic formulation used as immunomodulator, galactagogue, aphrodisiac and rejuvenator. Estimation of diagnostic characters of each ingredient of Shatavaryadi churna individually was carried out. Microscopic determination, counting of identifying number, measurement of area, length and breadth of identifying characters were performed using Leica DMLS-2 microscope. The method was validated for intraday precision, linearity, specificity, repeatability, accuracy and system suitability, respectively. The method is simple, precise, sensitive, and accurate, and can be used for routine standardisation of raw materials of herbal drugs. This method gives the ratio of individual ingredients in the powdered drug so that any adulteration of genuine drug with its adulterant can be found out. The method shows very good linearity value between 0.988-0.999 for number of identifying character and area of identifying character. Percentage purity of the sample drug can be determined by using the linear equation of standard genuine drug.

Effect of seabuckthorn extract on scopolamine induced cognitive impairment.

Present study involves evaluation of effects of 75% ethanolic extract of seabuckthorn [Hippophae rhamnoides L. (SBT)] leaves on scopolamine induced cognitive impairment in rats using three different oral doses i.e. 50, 100 and 200 mg/kg body weight through assessment of various biochemical and behavioural parameters. Scopolamine administration resulted in an increase in acetylcholinesterase (AChE) activity (approximately 9% with respect to the control group) and malonaldehyde (MDA) content. The increased AChE activity was significantly reduced in animals receiving 200 and 100 mg/kg of SBT extract. Animals treated with SBT extract showed significantly reduced MDA level in all the doses. This reduction in MDA content indicates that SBT leaf extract has potent antioxidant activities and exhibits a protective effect against oxidative damage induced by scopolamine. Behavioural studies also indicated significant improvement. The results suggest that SBT leaf extract has potential effects against scopolamine induced cognitive impairment by regulating cholinergic marker enzyme activity (AChE activity) and promoting the antioxidant system and may be explored for its use in cognitive disorders.