Antiobesity effects of phytochemicals from an epigenetic perspective.

Obesity is an important cause of morbidity and mortality due to its close association with metabolic disorders including diabetes, cardiovascular diseases, and certain types of cancer. According to the Developmental Origins of Adult Health and Disease hypothesis, obesity is likely caused by epigenetic changes. Recent studies have shown an association between epigenetic dysregulation of certain genes and obesity. Due to their reversible characteristic, epigenetic dysregulations can be restored. Restoration of epigenetic dysregulation in obesity-related genes by epigenetic modifiers may be a new treatment option for obesity. Certain phytochemicals such as tea polyphenols, curcumin, genistein, isothiocyanates, and citrus isoflavonoids were shown to prevent weight gain. These phytochemicals are known for their antioxidant effects but they also modify epigenetic mechanisms. These phytochemicals may have a therapeutic potential in the management of obesity. The aim of this study was to review the epigenetic effects of certain phytochemicals on the expression of obesity-related genes.

Mucoadhesive bilayered buccal platform for antifungal drug delivery into the oral cavity.

A drug delivery technology comprising a mucoadhesive bilayered buccally anchored tablet containing natamycin was developed. The concept was to anchor the tablet to the buccal tissue and allow controlled release of the drug through the matrix into the mouth. Carbomer (Carbopol ® 974 P NF) was used to formulate the mucoadhesive layer. Hydroxypropyl methylcellulose (HPMC) (Methocel® K4M) at 10, 15, 20, and 40% w/w was used for the drug-containing layer. Natamycin, an amphoteric macrolide antifungal agent, was incorporated into the formulations. In addition, tablets containing erythrosine as a marker were prepared in order to examine the distribution and retention of the dye in the oral cavity. As expected, the in vitro analysis showed that the concentration of natamycin released decreased with the increasing proportion of HPMC in the formulation. A small volunteer study was conducted using the tablets containing 10% and 20% HPMC to quantitate the patterns of distribution of the drug released into the oral cavity (upper right buccal vestibule, lower right and left buccal vestibules, and sublingual region). The mucoadhesive bilayered buccal tablet formulation provided a unidirectional release of the drug from the tablet into the oral cavity in a prolonged release fashion, maintaining drug concentration above the MIC value (2 µg/mL) for Candida albicans. The amount of the drug in the sublingual region was found to be lowest when compared with other regions, which is due to the higher flow of saliva in this region. Graphical abstract.

Chitosan-based particulate systems for drug and vaccine delivery in the treatment and prevention of neglected tropical diseases.

Neglected tropical diseases (NTDs) are a diverse group of infections which are difficult to prevent or control, affecting impoverished communities that are unique to tropical or subtropical regions. In spite of the low number of drugs that are currently used for the treatment of these diseases, progress on new drug discovery and development for NTDs is still very limited. Therefore, strategies on the development of new delivery systems for current drugs have been the main focus of formulators to provide improved efficacy and safety. In recent years, particulate delivery systems at micro- and nanosize, including polymeric micro- and nanoparticles, liposomes, solid lipid nanoparticles, metallic nanoparticles, and nanoemulsions, have been widely investigated in the treatment and control of NTDs. Among these polymers used for the preparation of such systems is chitosan, which is a marine biopolymer obtained from the shells of crustaceans. Chitosan has been investigated as a delivery system due to the versatility of its physicochemical properties as well as bioadhesive and penetration-enhancing properties. Furthermore, chitosan can be also used to improve treatment due to its bioactive properties such as antimicrobial, tissue regeneration, etc. In this review, after giving a brief introduction to neglected diseases and particulate systems developed for the treatment and control of NTDs, the chitosan-based systems will be described in more detail and the recent studies on these systems will be reviewed. Graphical abstract.

Development and in vitro evaluation of a new adjuvant system containing Salmonella Typhi porins and chitosan.

In order to improve the immunogenicity of the highly purified vaccine antigens, addition of an adjuvant to formulation, without affecting the safety of the vaccine, has been the key aim of the vaccine formulators. In recent years, adjuvants which are composed of a delivery system and immunopotentiators have been preferred to induce potent immune responses. In this study, we have combined Salmonella Typhi porins and chitosan to develop a new adjuvant system to enhance the immunogenicity of the highly purified antigens. Cationic gels, microparticle (1.69 ± 0.01 µm) and nanoparticles (337.7 ± 1.7 nm) based on chitosan were prepared with high loading efficiency of porins. Cellular uptake was examined by confocal laser scanning microscopy, and the macrophage activation was investigated by measuring the surface marker as well as the cytokine release in vitro in J774A.1 macrophage murine cells. Porins alone were not taken up by the macrophage cells whereas in combination with chitosan a significant uptake was obtained. Porins-chitosan combination systems were found to induce CD80, CD86 and MHC-II expressions at different levels by different formulations depending on the particle size. Similarly, TNF-α and IL-6 levels were found to increase with porins-chitosan combination. Our results demonstrated that combination of porins with chitosan as a particulate system exerts enhanced adjuvant effect, suggesting a promising adjuvant system for subunit vaccines with combined immunostimulating activity.

Localized drug delivery with mono and bilayered mucoadhesive films and wafers for oral mucosal infections.

Local drug delivery into oral cavity offers many advantages over systemic administration in treatment of the oral infections. In this study, monolayer and bilayered mucoadhesive film and wafer formulations were developed as local drug delivery platforms using chitosan and hydroxypropyl methylcellulose (HPMC). Cefuroxime axetil (CA) was used as the model drug. Surface morphology, mechanical strength, water uptake, in vitro adhesion, disintegration and in vitro release properties of the formulations were investigated. Furthermore, antimicrobial activity of the formulations was evaluated against E. coli and S. aureus. HPMC based formulations were found to disintegrate within <30 min whereas chitosan based formulations remained intact up to 6 h. Significantly higher drug release was obtained with wafer formulations. Antimicrobial activity was found to increase in presence of chitosan, and HPMC was also observed to contribute to this action. Bilayered wafer formulation, with adhesive chitosan backing layer and HPMC based drug loaded layer, providing prolonged drug release and suitable adhesive properties, with suitable mechanical strength, would be suggested as a promising local delivery system for treatment of the infections in the oral cavity.

DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors.

Oxidative stress and defective DNA repair are major contributory factors in the initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause oxidative DNA damage, consume antioxidant capacity, and impair DNA repair activity. These effects of chemotherapy and radiotherapy may be contributory factors in the development of secondary malignancy in cancer survivors. Basal, H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as a marker of oxidatively damaged DNA; and serum total antioxidant capacity were measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and H2O2-induced DNA damage were found to be higher in the ALL survivor group versus the control group, however, there was no significant difference between the other parameters. No association was found between the examined parameters and polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele was found to be associated with a low level of postrepair DNA damage in the ALL survivors. In conclusion, basal DNA damage and susceptibility to oxidation are high in childhood ALL survivors. This situation which may easily lead to occurrence of a secondary cancer does not seem to be a result of deficient DNA repair.