This study developed a new dual delivery system of naringenin (NRG), a polyphenol, and doxofylline (DOX), a xanthine derivative, as an inhaled microsphere system. In this system, NRG has been first loaded into glyceryl tristearate-based solid lipid nanoparticles (NRG SLN), which were further loaded with DOX into swellable chitosan-tripolyphosphate-based microspheres (NRG SLN DOX sMS). The system was characterized based on particle size, PDI, zeta potential, surface morphology (SEM, AFM, and TEM), solid-state and chemical properties (XRD, IR, and NMR), aerodynamic parameters, drug loading, entrapment efficiency and in vitro drug release study. The optimized NRG SLN DOX sMS exhibited particle size, zeta potential, and PDI of 2.1 µm, 31.2 mV, and 0.310, respectively; a drug entrapment efficiency > 79 %; a drug loading efficiency > 13 %; cumulative drug releases of about 78 % for DOX and 72 % for NRG after 6 and 12 h, respectively; good swelling and desirable aerodynamic properties. In addition, in vivo studies conducted in mice, a murine model of asthma showed significant reductions in serum bicarbonate and eosinophil counts and improvement in respiratory flow rate, tidal volume, and bronchial wall lining compared with the asthmatic control group. Overall, this novel inhalable dual-delivery system may represent a good alternative for the effective treatment of asthma.
Nanocapsules are polymeric nanoparticles encased in a polymeric coating composed of a predominantly non-ionic surfactant, macromolecules, phospholipids, and an oil core. Lipophilic drugs have been entrapped using various nanocarriers, including lipid cores, likely lipid nanocapsules, solid lipid nanoparticles, and others. A phase inversion temperature approach is used to create lipid nanocapsules. The PEG (polyethyleneglycol) is primarily utilised to produce nanocapsules and is a critical parameter influencing capsule residence time. With their broad drug-loading features, lipid nanocapsules have a distinct advantage in drug delivery systems, such as the capacity to encapsulate hydrophilic or lipophilic pharmaceuticals. Lipid nanocapsules, as detailed in this review, are surface modified, contain target-specific patterns, and have stable physical and chemical properties. Furthermore, lipid nanocapsules have target-specific delivery and are commonly employed as a marker in the diagnosis of numerous illnesses. This review focuses on nanocapsule synthesis, characterisation, and application, which will help understand the unique features of nanocapsules and their application in drug delivery systems.
Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics.
Current evidence of concept analyses recommending nanotechnology for biomedical uses abounds in recent research. The area of biotechnology interfaces with nanostructures, reconfigures their composition, and alters their characteristics; which influences the dispersion of the particles, the biotransformation they cause, and their potential toxic effect. It is vital to link the idea of the lifecycle of nanostructures to the biological impacts and use methodologies to identify, estimate, and track the gradual bioprocessing of nanostructures in vivo, from a body-wide level to a nanoscopic size. This is necessary because understanding how nanostructures processing, degradation, persistence, and recycling predict potential exposure risks. The safe implementation of nanotechnology-based products in biomedical applications necessitates an extensive understanding of the recycling and transformations of nanomaterials in a living organism. Long-term fate in the body is crucial, as it governs potential environmental risks to human health. Strategies may be used to manage the long-term outcome of nanostructures in an organism since, in addition to composition, their design also affects how long they last and how easily they degrade. The lifespan of nanoparticles, a flexible and biocompatible category of nanostructures that have made it into clinical trials, is the subject of this article. Strategies may be used to manage the long-term outcome of nanoparticles in an organism since, in addition to composition, their design also affects how long they last and how easily they degrade. This review explained the safety of nanoscale materials, biotransformation, and the multifunctional recycling mechanism of nanostructures.
Phytochemicals have the potential to treat resistant cancer. They are delivered to the target site via nano-based carriers. Promising results are seen in preclinical and in vitro models, as phytochemical-based nanoformulations have im-proved cell cytotoxicity compared to single agents. They can synergistically inhibit cancer cell growth through p53 apoptosis in MCF-7 breast cancer cell lines. Moreover, synergic viability in reproducible glioma models at half inhibitory concentra-tions has been shown. Through caspase activation, phytochemical-based nanoformulations also increase cell death in 4T1 breast cancer cell lines. They have shown improved cytotoxicity at half inhibitory concentrations compared to single-agent drugs in cervical cancer. In terms of colorectal cancer, they have the potential to arrest cells in the S phase of the cell cycle and synergistically inhibit cell proliferation. In squamous cell carcinoma of the tongue, they inhibit protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathways. This review reports on developments in the therapeutic management of various cancers using phytochemical-based nanoformulations, which have shown potential benefits in the clinical manage-ment of cancer patients, halting/slowing the progression of the disease and ameliorating chemotherapy-induced toxicities.
Abstract Purpose The present study describes oral administration of glyburide (GLY) and vanillic acid (VA) loaded polymeric micelles for the effective treatment of type 2 diabetes mellitus in high-fat diet (HFD) and a low dose of streptozotocin (STZ) rats. Methods The rats were divided into 12 groups (G1-G12) based on the respective treatments. All rats except G1 received high fat diet for first 15 days and then induced to STZ. Then the study was continued for another 28 days. GLY and VA loaded polymeric micelles (GV-APMs) were orally administered to the STZ induced rats. The rats of different groups received their respective treatments orally. Various parameters such as body weight, blood glucose level, biochemical parameters and histopathology of liver and pancreas. The rats of G2 received HFD-STZ alone, whereas rats of G6 received high dose of mixture of raw Gly-VA and G12 received high doses of GV-APMs, separately. Results The results revealed 1.43, 1.44, 1.55, 2.4, 1.66, 3.30, and 3.76-folds higher reduction in blood glucose, cholesterol (CHL), triglycerides, low-density lipoprotein (LDL), very LDL levels, CHL/high-density lipoprotein (HDL), and LDL/HDL ratio in rats receiving GV-APMs (G12) than rats receiving their physical mixture (G6). In addition to this, significant reduction in the serum inflammatory, hepatic and renal markers as well as antioxidant levels was observed in rats of G12 as compared to any other group, indicating higher efficacy of GV-APMs. Conclusion The study revealed that co-loading of GLY and VA in APMs showed excellent antidiabetic potential can be explored further for clinical evaluation.
Chemists found Imidazole as a multipurpose nucleus, primarily notable for its biological role in drug discovery. This compilation of the reports gives information regarding the development and the previous background of the synthesis of the nucleus. However, the synthesis through multicomponent is taken to narrow the report. The importance of the multicomponent reactions with many nucleus has been part of the heavy literature; however, the synthesis of the bioactive scaffold as imidazole has been highlighted here with the essential points. The emphasis of the review is to show the multicomponent approach where the multicomponent reaction plays a vital role in the formation of the ring. The MCR approaches align with modern-day drug discovery, where the library of the molecules is needed for drug development within a limited time frame. The multicomponent also comes under the green chemistry, where the reaction time and fewer reactions step plays a crucial role.
In the present study, the extract from the stem of Euphorbia neriifolia was used to investigate its antioxidant and antidiabetic activity. The antidiabetic potential of Euphorbia neriifolia was investigated in streptozotocin-induced diabetic rats. Standard phytochemical methods were used for qualitative and quantitative phytochemical studies. The scavenging activity of 2,2-diphenyl-2-picrylhydrazyl and hydrogen peroxide was used to study the antioxidant activity of hydroalcoholic extract of Euphorbia neriifolia (HAE). Plasma glucose content, lipid profiles, insulin levels, GLUT-4 protein content in muscle homogenates, inhibition of amylase and pancreatic glucosidase, and pancreatic histology were measured in control and diabetic rats. HAE was revealed its antidiabetic effect via inhibition of α-amylase and α-glucosidase. In the treated groups, glucose and insulin level was found significant as compared to diabetic control. Histology also disclosed normalization of pancreatic histoarchitecture. The number of β-cells in the islets increased, indicating that they were renewed, increasing insulin secretion and better utilization in muscle by increasing GLUT-4 transporter in the treated groups. Therefore, it was concluded that co-treatment (Glibenclamide 5 mg/kg + HAE 100 mg/kg) exert synergistic antidiabetic effect.
In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in humans. Monkeypox can be prevented and controlled with a better understanding of MPXV's molecular etiology and epidemiological and clinical features. In light of the current outbreaks worldwide, we provide updated information on monkeypox for medical professionals in this review.
Cancer is the leading cause of human disease and death worldwide, accounting for 7.6 million deaths per year and projected to reach 13.1 million by 2030. Many phytochemicals included in traditional medicine have been utilized in the management of cancer. Conventional chemotherapy is generally known to be the most effective treatment of metastatic cancer but these cancerous cells might grow resistant to numerous anticancer drugs over time that resulting in treatment failure. This review tried to portray the advancement in the anticancer and chemopreventive effects of several phytochemicals and some of its members encapsulated in the nano-based delivery system of the drug. It comprises the issue associated with limited use of each phytoconstituents in human cancer treatment are discussed, and the benefits of entrapment into nanocarriers are evaluated in terms of drug loading efficiency, nanocarrier size, release profile of the drug, and in vitro and/or in vivo research and treatment testing, such as cytotoxicity assays and cell inhibition/viability.
Increasing obesity has become a serious health problem worldwide in recent years, both in adults and children. Obesity can lead to numerous diseases such as osteoarthritis, diabetes, cardiovascular and respiratory diseases, and other metabolic disorders. In addition, obesity is considered one of the most common causes of insulin resistance in the body. Moreover, obesity disrupts normal insulin physiology, resulting in impaired insulin signaling and other intrinsic abnormalities such as poor glucose movement, phosphorylation, and decreased glucose oxidation and glycogenesis. Therefore, it is necessary to find an effective treatment for such conditions. Recently, exosomal therapy has been proposed as one of the alternative approaches to treat metabolic diseases. Exosomes are endosome-derived extracellular vesicles that circulate in body fluids such as mucus, blood plasma, urea, etc., transfer molecules and signals from one cell to another, and thus are involved in various normal and pathological processes in the human body. It has been discovered that exosomes play a role in processes related to obesity, such as adipocyte differentiation, angiogenesis, inflammation, etc. The current study reviewed exosomes’ role in the development of insulin resistance associated with obesity and possible targets.
Cancer is characterized by disrupted molecular variables caused by cells that deviate from regular signal transduction. The uncontrolled segment of such cancerous cells annihilates most of the tissues that contact them. Gene therapy, immunotherapy, and nanotechnology advancements have resulted in novel strategies for anticancer drug delivery. Furthermore, diverse dispersion of nanoparticles in normal stroma cells adversely affects the healthy cells and disrupts the crosstalk of tumour stroma. It can contribute to cancer cell progression inhibition and, conversely, to acquired resistance, enabling cancer cell metastasis and proliferation. The tumour's microenvironment is critical in controlling the dispersion and physiological activities of nano-chemotherapeutics which is one of the targeted drug therapy. As it is one of the methods of treating cancer that involves the use of medications or other substances to specifically target and kill off certain subsets of malignant cells. A targeted therapy may be administered alone or in addition to more conventional methods of care like surgery, chemotherapy, or radiation treatment. The tumour microenvironment, stromatogenesis, barriers and advancement in the drug delivery system across tumour tissue are summarised in this review.
This study highlights the importance of community pharmacists' strategic role in hindering the progression of the SARS-CoV-2 virus in the community setting and innovative measures to protect themselves. This article focuses on the features, control, and prevention of COVID-19 and social awareness measures of the pandemic. The means employed by the community pharmacist to safeguard his health while providing pharmaceutical services during COVID-19 is compiled and presented to benefit health-care professionals around the world. As per the US Center for Disease Control and Prevention, community pharmacists play a crucial role in providing essential drugs to patients without knowing their current COVID-19 status. They also work in conditions that make them susceptible to COVID-19 exposure. Despite the availability of guidelines, community pharmacists need to be trained in personal protective equipment for efficient protection and prevention of spread. Community pharmacists are essential frontline warriors against transmission of the SARS-CoV-2 virus in the community and act as frontline workers to educate the public on COVID-19. They are at high risk and need to observe necessary precautions to mitigate the spread of the virus.
There is a significant difference between COVID 19 associated mortality between different countries. Generally the number of deaths per million population are higher in the developed countries despite better health care efficiency, drinking water quality and expected healthy life span (HALE) at the time of birth. Developing and underdeveloped countries on the other hand have lower mortality even with higher rural and slum populations along with incidence of diarrhea because of lack of sanitation. We analyzed data from 122 countries out of which 80 were high or upper middle income and 42 were low or low middle income countries. There was statistically significant positive correlation between COVID 19 deaths /million population and water current score, health efficiency, and HALE. Statistically significant negative correlation was observed with % rural population and fraction of diarrhea because of inadequate sanitation for all ages. Moreover analysis of 51 countries showed that there is significant negative correlation between COVID 19 deaths /million population and proportion of total population living in slums. We propose that high microbial exposure particularly gram negative bacteria can possibly induce interferon type I which might have a protective effect against COVID 19 since the countries with less mortality also tend to have lack of sanitation and high incidence of attendant diseases. So, far none of the predictive models have taken into account immune status of populations engendered by environmental microbial exposure or microbiome. There might be a need to look at dynamics of COVID 19 pandemic using immune perspective. The approach can potentially inform better policies including interventions.
Objective: Transdermal patch of timolol maleate was prepared in order to increase the permeability of the drug topically. Methods: The timolol maleate (TM) loaded solid lipid nanoparticles (SLN) were prepared by the solvent evaporation method. For the optimization process full factorial (three-factor and three-level), hydroxypropyl methylcellulose (HPMC) range from 100 to 300 mg, ethylcellulose 100 to 200 gm and almond oil 3 to 4 ml. The response noted in form of tensile strength and percent drug release. These transdermal patches were evaluated for physical characterization like weight variation, thickness, percentage moisture absorption, percentage moisture loss, water vapor transmission rate, folding endurance, tensile strength, and content uniformity. Results: Solid lipid nanoparticles of TM were optimized and prepared, the data presented that drug release percent ranged from 66.12 to 91.75. 2FI model was observed to fit for response % drug permeation with a p and F value of 0.0271 and 4.50. The tensile strength varies from 0.358 to 0.508. The linear model was observed to fit for the tensile strength response with a p-value and F-value of<0.0001 and 52.41. Conclusion: The controlled release formulation of Timolol Maleate was successfully optimized and prepared, a study conducted to investigate the effect of different polymers and type of permeation time profiles from Timolol Maleate patches.
The rationale of the current work was to evaluate antihypertensive activity ofTimolol maleate nanoparticles loaded transdermal patch.Nanoparticles loaded transdermal patch of timolol maleate was prepared using Compritol 888, Lutrol F68, tween 80 etc.The formulated patches were subjected to skin irritation study and in-vivo antihypertensive activity.Hypertension was induced by dexamethasone in experimental rats.No any marked skin irritation observed before and after applying the patch.Both systolic and diastolic blood pressure in experimental animals was reduced significantly after 7 days treatment with Timolol maleate nanoparticles loaded transdermal patch.So, it was concluded that timolol maleate patch could be formulated into a matrix-type naoparticle loaded transdermal patch for the management of hypertension.Also, this study can be considered as a new report that focuses on the problem of the side-effects associated with the modern medicaments toward hypertension
In current investigation an attempt has been made to formulate and evaluate Quinapril mouth dissolving films using HPMC 50cps, E5, E15 and in combination of Pullulan by Solvent evaporation method. Sodium starch glycolate acts as a super disintegrating agent and it is shown that as the concentration of the super disintegrates increases the disintegration time decreases. The films were evaluated for weight variation, surface pH, folding endurance, drug content, dissolving time, disintegration time, and in-vitro dissolution studies. Based on the evaluation parameters F17 was to be optimized formulation. The optimized film (F17) showed the more drug release i.e 99.40 ± 5.30% within 7 min, lowest in vitro disintegration time 10 sec. FTIR studies proved no drug polymer interaction takes place. These results revealed that fast dissolving films of Quinapril could be formulated for quick onset of action which is required in the efficient management of hypertension.
In current investigation an attempt has been made to formulate and evaluate Quinapril mouth dissolving films using HPMC 50cps, E5, E15 and in combination of Pullulan by Solvent evaporation method.Sodium starch glycolate acts as a super disintegrating agent and it is shown that as the concentration of the super disintegrates increases the disintegration time decreases.The films were evaluated for weight variation, surface pH, folding endurance, drug content, dissolving time, disintegration time, and in-vitro dissolution studies.Based on the evaluation parameters F17 was to be optimized formulation.The optimized film (F17) showed the more drug release i.e 99.40±5.30%within 7 min, lowest in vitro disintegration time 10 sec.FTIR studies proved no drug polymer interaction takes place.From in vivo bioavailability studies, Cmax of the optimized formulation F17 was 72.43±0.3ng/ml, was significantly higher as compared to pure drug suspension, i.e., 42.32±0.1ng/ml.Tmax of optimized formulation was decreased significantly when compared with pure drug (1.00±0.05hr,2.00±0.1hr),AUC0-∞ and AUC0-t for optimized films was significantly higher (p<0.05) as compared to marketed product.These results revealed that fast dissolving films of Quinapril could be formulated for quick onset of action which is required in the efficient management of hypertension.