Porozne nanočestice metoprolol tartarata dobivene pomoću sušenja sprejanjem: Razvoj, karakterizacija i evaluacija in vitro

The present investigation was undertaken to fabricate porous nanoparticles of metoprolol tartrate by spray-drying using ammonium carbonate as pore former. Prepared nanoparticles were coated with Eudragit S100 polymer in order to prevent the release of metoprolol tartrate in the upper GI tract. It was shown that nanoparticles with low size ranges can be obtained with a low feed inlet rate. Micromeritic studies confirmed that nanoparticle batches are discrete and free flowing. Effects of the pore former on drug loading, porosity and in vitro release were studied. It was found that there was an increase in drug loading and porosity with increased the amount of pore former. In vitro drug release studies showed that an increase in pore former made drug release faster. Release kinetics proved that nanoparticles follow a zero-order release mechanism.U radu je opisana priprava poroznih nanočestica metoprolol tartarata pomoću sušenja sprejanjem, koristeći amonijev karbonat za stvaranje pora. Da bi se spriječilo oslobađanje metoprolol tartarata u gornjem dijelu GI trakta, nanočestice su obložene polimerom Eudragit S100. Nanočestice podjednake veličine mogu se dobiti polaganim uklapanjem ljekovite tvari. Mikromeričke studije potvrdile su da su nanočestice zasebne i tečne. Proučavan je utjecaj sredstva za stvaranje pora na količinu uklopljenog lijeka, poroznost i in vitro oslobađanje. Povećanje količine sredstva za stvaranje pora povećava količinu uklopljenog lijeka, poroznost i brzinu oslobađanja ljekovite tvari. Oslobađanje metoprolola slijedi kinetiku nultog reda

Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity

Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity

Development and evaluation of porous tablets of sodium alginate for <span style="font-size:15.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-ansi-language:EN-IN;mso-fareast-language:EN-IN; mso-bidi-language:AR-SA">treatment of Enterotoxigenic <i>Escherichia coli </i>infection</span>

179-185Enterotoxigenic Escherichia coli (ETEC) infections result in large mortality rate and usually a frequent cause of diarrhea in infants. To prevent enterotoxigenic escherichia coli infections animal needs an active mucosal immunity at the moment of weaning. In the present study, F4 loaded porous sodium alginate tablets were prepared by direct compression technique for oral vaccination using ammonium carbonate as a pore former. In order to prevent the release the antigen in upper GI tract and to release it at target site nanoparticles were coated with Eudragit S100 which will protect the antigen against the detrimental effects in the gastrointestinal tract. Tablets were evaluated for pharmaco-technical properties and results were found to be satisfactory. SEM studies were conducted in order to show the porous surface of tablets. Ammonium carbonate as a pore forming agent proves to be promising and was successful in creating pores on surface of tablets through which F4 was loaded in tablets. SEM had given a clear picture showing major and minor pore with different pore size. It was found that an increase in pore forming agent leads to decrease in hardness and disintegration time of porous tablets. Mucosal immune response study revealed that, immune response was elicited and animals vaccinated with porous tablets group shows a significant reduction in excretion of F4+ E coli. Studies indicate that a solid vaccine formulation will be more efficient and these systems can contribute to the development of oral vaccines in veterinary as well as in human medicines

Antifungal response of or-al-associated candidal reference strains (American Type Culture Collection) by supercritical fluid extract of nutmeg seeds for geriatric denture wearers: An in vitro screening study

Objectives: Since time immemorial, plants have continued to play a predominant role in the maintenance of human health as sources of medicinal compounds. Several effective antifungal agents are available for oral Candida infections; the failure is not uncommon because isolates of Candida albicans may exhibit resistance to the drug during therapy. The present study aimed to identify an alternative, inexpensive, simple, and effective method of preventing and controlling the candidal infection. Methodology: All the procured and authenticated nutmeg seeds were dried in shade and cleaned by hand sorting. The crushed seeds were passed through mesh no. 40 individually. About 50 g of powdered nutmeg seeds was loaded in the supercritical fluid extractor unit using supercritical CO2 as extracting solvent in accordance with the methods of Nguyen et al. Supercritical fluid (SFE) extraction was done using CO2 gas without any cosolvents. Results: The nutmeg extract displayed antifungal activity with the effective zone of inhibition ranging from 18.0 to 12.0 mm when compared with nystatin as positive control. Conclusion: This paper described the in vitro antibacterial activity, and phytochemical analysis of SFE extract of nutmeg (Myristica fragrans) evaluated against C. albicans (American Type Culture Collection 10231) through agar well diffusion method. SFE of nutmeg seeds can be used as an adjunct to conventional therapy for oral candidiasis

Biomedical applications of phytomedicines: Dental perspective

Introduction: Ayurveda is the ancient Indian system of health care and longevity. Ayurvedic treatment is aimed at the patient as an organic whole, and treatment consists of salubrious use of drugs, diets, and certain practices. Currently, Ayurveda is widely practiced in the Hindustan peninsula (India and the neighboring countries) and in recent years, there has been a resurgence of herbs in economically developed countries such as those in Europe, United States, and Japan. Methods: A comprehensive literature search was made in PubMed, MEDLINE, LILACS/BBO, Cochrane Database of Systematic Reviews, sciencedirect, and Google Scholar databases. Results: Herbs have been used for centuries to prevent and control disease. Herbal extracts are effective because they interact with specific chemical receptors within the body and are in a pharmacodynamics sense, drugs themselves. Taking into consideration the ineffectiveness, potential side effects, and safety concerns of synthetic drugs, the herbal alternatives for dental usage might prove to be advantageous. Conclusion: Phytomedicine has been used in dentistry as an anti-inflammatory, antibiotic, analgesic, sedative and also as endodontic irrigant. Herbal preparations can be derived from the root, leaves, seeds, stem, and flowers

Nanodelivery Systems Targeting Epidermal Growth Factor Receptors for Glioma Management

A paradigm shift in treating the most aggressive and malignant form of glioma is continuously evolving; however, these strategies do not provide a better life and survival index. Currently, neurosurgical debulking, radiotherapy, and chemotherapy are the treatment options available for glioma, but these are non-specific in action. Patients invariably develop resistance to these therapies, leading to recurrence and death. Receptor Tyrosine Kinases (RTKs) are among the most common cell surface proteins in glioma and play a significant role in malignant progression; thus, these are currently being explored as therapeutic targets. RTKs belong to the family of cell surface receptors that are activated by ligands which in turn activates two major downstream signaling pathways via Rapidly Accelerating Sarcoma/mitogen activated protein kinase/extracellular-signal-regulated kinase (Ras/MAPK/ERK) and phosphatidylinositol 3-kinase/a serine/threonine protein kinase/mammalian target of rapamycin (PI3K/AKT/mTOR). These pathways are critically involved in regulating cell proliferation, invasion, metabolism, autophagy, and apoptosis. Dysregulation in these pathways results in uncontrolled glioma cell proliferation, invasion, angiogenesis, and cancer progression. Thus, RTK pathways are considered a potential target in glioma management. This review summarizes the possible risk factors involved in the growth of glioblastoma (GBM). The role of RTKs inhibitors (TKIs) and the intracellular signaling pathways involved, small molecules under clinical trials, and the updates were discussed. We have also compiled information on the outcomes from the various endothelial growth factor receptor (EGFR)&ndash;TKIs-based nanoformulations from the preclinical and clinical points of view. Aided by an extensive literature search, we propose the challenges and potential opportunities for future research on EGFR&ndash;TKIs-based nanodelivery systems

Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity

Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity.Peer reviewe

Development and Evaluation of Clove and Cinnamon Supercritical Fluid Extracts-Loaded Emulgel for Antifungal Activity in Denture Stomatitis

Denture stomatitis (DS), usually caused by Candida infection, is one of the common denture-related complications in patients wearing dentures. Clove and cinnamon oils have been acknowledged for their anti-inflammatory, antimicrobial activity, and antifungal effects in the oral cavity. The aim of this study, therefore, was to prepare clove/cinnamon oils-loaded emulgel and to assess its efficacy in treating Candida albicans-associated denture stomatitis. Central composite design was adopted to formulate and optimize clove/cinnamon extracts-loaded emulgel. The formulated preparations were assessed for their physical appearance, particle size, viscosity, spreadability, and in-vitro drug release. In addition, in-vivo therapeutic experiments were conducted on 42 patients with denture stomatitis. The prepared emulgel formulations showed good physical characteristics with efficient drug release within 3 h. In addition, in-vivo antifungal studies revealed that the optimized formula significantly (p &lt; 0.001) reduced Candida colony counts from the denture surface, compared to commercially available gel (240.38 &plusmn; 27.20 vs. 398.19 &plusmn; 66.73 CFU/mL, respectively). Furthermore, the optimized formula and succeeded in alleviating denture stomatitis-related inflammation with a better clinical cure rate compared to commercially available gel Collectively, herbal extracts-loaded emulgel might be considered an evolution of polyherbal formulations and might represent a promising alternative to the existing allopathic drugs for the treatment of denture stomatitis, with better taste acceptability and no side effects

Microneedles Drug Delivery Systems for Treatment of Cancer: A Recent Update

Microneedles (MNs) are tiny needle like structures used in drug delivery through layers of the skin. They are non-invasive and are associated with significantly less or no pain at the site of administration to the skin. MNs are excellent in delivering both small and large molecules to the subjects in need thereof. There exist several strategies for drug delivery using MNs, wherein each strategy has its pros and cons. Research in this domain lead to product development and commercialization for clinical use. Additionally, several MN-based products are undergoing clinical trials to evaluate its safety, efficacy, and tolerability. The present review begins by providing bird&rsquo;s-eye view about the general characteristics of MNs followed by providing recent updates in the treatment of cancer using MNs. Particularly, we provide an overview of various aspects namely: anti-cancerous MNs that work based on sensor technology, MNs for treatment of breast cancer, skin carcinoma, prostate cancer, and MNs fabricated by additive manufacturing or 3 dimensional printing for treatment of cancer. Further, the review also provides limitations, safety concerns, and latest updates about the clinical trials on MNs for the treatment of cancer. Furthermore, we also provide a regulatory overview from the &ldquo;United States Food and Drug Administration&rdquo; about MNs