Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible. CONCLUSIONS: Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain.

Toxicity of nanoparticle surface coating agents: Structure-cytotoxicity relationship.

Surface coating agents for metal nanoparticles, cationic alkyl ammonium bromides, and anionic alkyl sulfates were tested against human skin keratinocytes (HaCaT) and blood T lymphocytes (TIB-152). The surfactants of short chain (C8) are not cytotoxic, but as chain length increases, their cytotoxicity increases and levels off at C12 for cationic surfactants against both cell lines and for anionic surfactants against the TIB-152, but C14 for anionic surfactants against HaCaT. The cationic surfactants are more toxic than the anionic surfactants for HaCaT; while with similar cytotoxicity for TIB-152 cells. di- and tetra-Alkyl ammonium salts are more cytotoxic than the mono-substituted.

Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics.

Chemotherapy-induced mucositis is a common condition caused by the breakdown of the mucosal barrier. Symptoms can include pain, vomiting and diarrhoea, which can often necessitate chemotherapy treatment breaks or dose reductions, thus compromising survival outcomes. Despite the significant impact of mucositis, there are currently limited clinically effective pharmacological therapies for the pathology. New emerging areas of research have been proposed to play key roles in the development of mucositis, providing rationale for potential new therapeutics for the prevention, treatment or management of chemotherapy-induced mucositis. This review aims to address these new areas of research and to comment on the therapeutics arising from them.

Surface Modification Strategies for Chrysin-Loaded Iron Oxide Nanoparticles to Boost Their Anti-Tumor Efficacy in Human Colon Carcinoma Cells.

Enhancing nanoparticles' anti-cancer capabilities as drug carriers requires the careful adjustment of formulation parameters, including loading efficiency, drug/carrier ratio, and synthesis method. Small adjustments to these parameters can significantly influence the drug-loading efficiency of nanoparticles. Our study explored how chitosan and polyethylene glycol (PEG) coatings affect the structural properties, drug-loading efficiency, and anti-cancer efficacy of Fe3O4 nanoparticles (NPs). The loading efficiency of the NPs was determined using FTIR spectrometry and XRD. The quantity of chrysin incorporated into the coated NPs was examined using UV-Vis spectrometry. The effect of the NPs on cell viability and apoptosis was determined by employing the HCT 116 human colon carcinoma cell line. We showed that a two-fold increase in drug concentration did not impact the loading efficiency of Fe3O4 NPs coated with PEG. However, there was a 33 Å difference in the crystallite sizes obtained from chitosan-coated Fe3O4 NPs and drug concentrations of 1:0.5 and 1:2, resulting in decreased system stability. In conclusion, PEG coating exhibited a higher loading efficiency of Fe3O4 NPs compared to chitosan, resulting in enhanced anti-tumor effects. Furthermore, variations in the loaded amount of chrysin did not impact the crystallinity of PEG-coated NPs, emphasizing the stability and regularity of the system.

Fluoride release by restorative materials after applying surface coating agents.

The prompt use of an enamel surface covering reagent is advised to safeguard the dental restorative substance from mishaps. Therefore, it is of interest to assess the fluoride emitting capabilities of standard GIC, and Zirconomer cement together with surface coverings and without surface coverings. The conventional GIC cement was part of experimental category A while Zirconomer cement was part of category B. For every experimental categories, a set of sixty brass mould prototypes in the form of disc with dimensions: diameter (6±0.1mm) and thickness (2±0.1 mm) were created and subsequently covered with Teflon strip in accordance with the package recommendations. Also, for both experimental categories, such pellets were randomly allocated to three sub-categories of 20 each. For one category petroleum jelly was administered with a cotton bud and then delicately dried under airflow (A3 subcategory and B3 subcategory); for another sub-category G-Coat was laced through a micro-tip dispenser and light treated for twenty seconds (A2 subcategory and B2 subcategory); the rest 20 specimens were left without any coating (A1 subcategory and B1 subcategory). It was observed that in subcategory A1 and A3 there was continuous decline in emission of fluoride ion as the days progressed. However there was an increase in emission of fluoride in A2 subcategory on moving to day 5 from day 1. However, from day 5 onwards decline in fluoride emission was observed in A2 subcategory. It was concluded that both materials studied (GIC and Zirconomer) exhibited fluoride emission whether or not they were surface-coated for protection.

Design and preparation of nanocomposite acrylate coating agents for binder-free dry coating of 100 µm-sized drug-containing particles and their coating performance.

For binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle. Dry coating of the IER-DS with nanocomposite coating agents was carried out using a laboratory-made coating apparatus assisted with mild-intensity vibration and zirconia bead impaction. The coated particles were cured by heating at a temperature 20 °C higher than the Tg for 12 h to complete the film-forming process. It was found that the highest coating efficiency (more than 70%) and a remarkably prolonged release period of the drug (the time required for 50% release reached approximately 12 h) could be achieved when nanocomposite coating agents with a soft polymeric core (Tg = 30 °C) and a hard polymeric shell (Tg = 80 °C) were applied. In contrast, nanocomposite coating agents with a combination of a hard polymeric core and a soft polymeric shell resulted in lower coating efficiency. These results demonstrate that nanocomposite polymeric coating agents composed of a soft core and a hard shell are effective for the production of drug-loaded microparticles with a prolonged release function by a binder-free dry-coating process.

Silver nanoparticles as a medical device in healthcare settings: a five-step approach for candidate screening of coating agents.

Silver nanoparticle-based antimicrobials can promote a long lasting bactericidal effect without detrimental toxic side effects. However, there is not a clear and complete protocol to define and relate the properties of the particles (size, shape, surface charge, ionic content) with their specific activity. In this paper, we propose an effective multi-step approach for the identification of a 'purpose-specific active applicability window' to maximize the antimicrobial activity of medical devices containing silver nanoparticles (Ag NPs) (such as surface coaters), minimizing any consequent risk for human health (safety by design strategy). The antimicrobial activity and the cellular toxicity of four types of Ag NPs, differing in their coating composition and concentration have been quantified. Through the implementation of flow-field flow fractionation, Ag NPs have been characterized in terms of metal release, size and shape. The particles are fractionated in the process while being left unmodified, allowing for the identification of biological particle-specific contribution. Toxicity and inflammatory response in vitro have been assessed on human skin models, while antimicrobial activity has been monitored with both non-pathogenic and pathogenic Escherichia coli. The main benefit associated with such approach is the comprehensive assessment of the maximal effectiveness of candidate nanomaterials, while simultaneously indexing their properties against their safety.

In vitro and in vivo evaluation of biologically synthesized silver nanoparticles for topical applications: effect of surface coating and loading into hydrogels.

In the present study, silver nanoparticles (AgNPs) were synthesized via biological reduction of silver nitrate using extract of the fungus Fusarium verticillioides (green chemistry principle). The synthesized nanoparticles were spherical and homogenous in size. AgNPs were coated with polyethylene glycol (PEG) 6000, sodium dodecyl sulfate (SDS), and ß-cyclodextrin (ß-CD). The averaged diameters of AgNPs were 19.2±3.6, 13±4, 14±4.4, and 15.7±4.8 nm, for PEG-, SDS-, and ß-CD-coated and uncoated AgNPs, respectively. PEG-coated AgNPs showed greater stability as indicated by a decreased sedimentation rate of particles in their water dispersions. The antibacterial activities of different AgNPs dispersions were investigated against Gram-positive bacteria (methicillin-sensitive and methicillin-resistant Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) by determination of the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). MIC and MBC values were in the range of 0.93-7.5 and 3.75-15 µg/mL, respectively, which were superior to the reported values in literature. AgNPs-loaded hydrogels were prepared from the coated-AgNPs dispersions using several gelling agents (sodium carboxymethyl cellulose [Na CMC], sodium alginate, hydroxypropylmethyl cellulose, Pluronic F-127, and chitosan). The prepared formulations were evaluated for their viscosity, spreadability, in vitro drug release, and antibacterial activity, and the combined effect of the type of surface coating and the polymers utilized to form the gel was studied. The in vivo wound-healing activity and antibacterial efficacy of Na CMC hydrogel loaded with PEG-coated AgNPs in comparison to the commercially available silver sulfadiazine cream (Dermazin®) were evaluated. Superior antibacterial activity and wound-healing capability, with normal skin appearance and hair growth, were demonstrated for the hydrogel formulations, as compared to the silver sulfadiazine cream. Histological examination of the treated skin was performed using light microscopy, whereas the location of AgNPs in the skin epidermal layers was visualized using transmission electron microscopy.

Nanocarriers for Effective Brain Drug Delivery.

Drug delivery to the brain is an engaged research topic in the field of nanomedicine. The passage of therapeutics into the brain parenchyma is more complicated than other body tissues due to it is limited by restrict barrier structure called blood-brain barrier (BBB). Nanotechnology holds great promise to overcome the BBB and thereby enable treatment of neurodegenerative diseases. Nanocarriers have been investigated several times as effective brain drug delivery systems in the past few decades. Physicochemical properties and surface modifications of these carriers play a significant role in terms of brain up-taking of nanocarriers. Chemical structures of possible nano sized drug delivery systems have an importance in terms of interactions between cell membranes of brain endothelial cell lines and these interactions can be modified with surface coating strategies using suitable agents. Particle size, surface charge and total molecular mass are also crucial issues which require special attention in order to better understand appropriate properties of nanocarriers to overcome the BBB structure. Different strategies have been demonstrated to facilitate the passage of nanoparticles into the brain parenchyma including attachment of targeting ligands on the nanoparticles' surfaces; this attempt provides site specific action in the brain tissues. This study aims to provide a review of nanocarriers for effective brain drug delivery, in the light of current literature.

Cytotoxicity of organic surface coating agents used for nanoparticles synthesis and stability.

Impact on health by nanomaterials has become a public concern with the great advances of nanomaterials for various applications. Surface coating agents are an integral part of nanoparticles, but not enough attention has been paid during toxicity tests of nanoparticles. As a result, there are inconsistent toxicity results for certain nanomaterials. In this study, we explored the cytotoxicity of eleven commonly used surface coating agents in two cell lines, human epidermal keratinocyte (HaCaT) and lung fibroblast (CRL-1490) cells, at surface coating agent concentrations of 3, 10, 30, and 100 µM. Two exposure time points, 2 h and 24 h, were employed for the study. Six of the eleven surface coating agents are cytotoxic, especially those surfactants with long aliphatic chains, both cationic (cetyltrimethylammonium bromide, oleylamine, tetraoctylammonium bromide, and hexadecylamine) and anionic (sodium dodecylsulfate). In addition, exposure time and the use of different cell lines also affect the cytotoxicity results. Therefore, factors such as cell lines used and exposure times must be considered when conducting toxicity tests or comparing cytotoxicity results.