Binary Dimeric Prodrug Nanoparticles for Self-Boosted Drug Release and Synergistic Chemo-Photodynamic Therapy

Chemotherapy is the major strategy for cancer therapy, but its limited therapeutic efficiency and serious toxicity to normal tissues greatly restrict its clinical performance. Herein, we develop carrier-free self-activated prodrug...

Bacteriological control of milk and effectiveness of antimastitis measures in cows

Under the current conditions of livestock development, the main task of farms is the systematic bacteriological control of milk and the development of comprehensive programs for the control and prevention of mastitis in cows. These measures will make it possible to establish control over this pathology, reduce veterinary treatment costs, improve milk quality, increase average hopes for lactation, increase the productive use of cows, and more. It was found that among the forms of clinical mastitis in the farm registered catarrhal and purulent-catarrhal (65.0 %), serous (12.0 %), and less often – fibrinous (11.5 %), hemorrhagic (11.0 %), and abscess udder (0.5 %). Bacteriological studies of milk taken from cows proved the presence of Staphylococcus saprophyticus, Escherichia coli, β-hemolytic Streptococcus spp. Microbiological studies showed that the isolated cultures of microorganisms were sensitive to tetracycline, neomycin, and cloxacycline; conditionally sensitive to streptomycin, doxycillin; no sensitivity to amoxicillin + clavulanic acid, norfloxacin and gatifloxacin. A treatment scheme was proposed for patients with purulent-catarrhal mastitis of cows, included intra-tank injections of the drug “Mastidev-Linko,” intramuscular injections of the drug “Tseftiodev 5%” and external application of the ointment “Dibutaliastin.” As a result of studies on the therapeutic efficiency of the proposed veterinary drugs when used in cows of Holstein-Friesian and black-spotted breed, patients with purulent-catarrhal mastitis, 91.6 % therapeutic efficiency of drugs was established. It is recommended that animals infected with infectious agents should be milked last and milking machines thoroughly disinfected; apply the pre- and post-milking treatment of udder teats with disinfectants (dips); periodically check in the laboratory the disinfecting ability of drugs for udder treatment and disinfection of accessories; use only proven tools; control the correct preparation of solutions and treatment of the udder with disinfectants (dips); to reject animals that do not respond to treatment (chronically ill).

Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second near-infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting and therapeutic efficiency of anti-epidermal growth factor receptor (EGFR)-antibody-functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro. Four cell lines, KYSE-30, CAL-27, Hep-G2 and MCF-7, which either over- or under-expressed EGFR, were used once confirmed by flow cytometry and immunofluorescence. Optical microscopy demonstrated a significant difference (p < 0.0001) between targeted AuNRs (tAuNRs) and untargeted AuNRs (uAuNRs) in all four cancer cell lines. This study demonstrated that anti-EGFR functionalisation significantly increased the association of tAuNRs with each EGFR-positive cancer cell. Considering this, the MTT assay showed that photothermal therapy (PTT) significantly increased cancer cell death (>97%) in head and neck cancer cell line CAL-27 using tAuNRs but not uAuNRs, apoptosis being the major mechanism of cell death. This successful targeting and therapeutic outcome highlight the future use of tAuNRs for molecular photoacoustic imaging or tumour treatment through plasmonic photothermal therapy.

Therapeutic Liquid Formulations Based on Low Transition Temperature Mixtures for the Incorporation of Anti-Inflammatory Drugs

Most nonsteroidal anti-inflammatory drugs (NSAIDs) present poor aqueous solubility, impairing their efficiency in physiological media. In this context, Low Transition Temperature Mixtures (LTTMs) are a promising platform to overcome drugs’ poor solubility, forming therapeutic liquid formulations. In this work, the LTTMs of citric acid:L-arginine:water (C:A:W) and glycerol:sorbitol (G:S) were studied in terms of their features and assessed in terms of their ability to increase the solubility of six NSAIDs in physiological media. The physicochemical properties of LTTMs were characterized by state-of-art techniques commonly used for these systems. The cytotoxicity of G:S was also evaluated in L929 mouse fibroblasts and the viscosity, polarity, and pH properties of the studied mixtures were related to the solubility of NSAIDs. The pH and polarity were the parameters that most influenced the drugs’ solubility. Ibuprofen, naproxen, ketoprofen, indomethacin, and flurbiprofen did not present any solubility improvement in the formulations tested. However, concentrated mixtures of C:A:W or G:S in the physiologic-mimicked media (PBS) rendered a celecoxib solubility 4 and 5 times higher than PBS, respectively. These therapeutic liquid formulations of celecoxib in C:A:W or G:S can be a promising tool to increase celecoxib’s therapeutic efficiency in local applications.

Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice

Background Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs. Methods Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone. Results The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella. Conclusions These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.