Doxorubicin (Dox) is an effective anti-cancer medication with poor oral bioavailability and systemic toxicities. DoxQ was developed by conjugating Dox to the lymphatically absorbed antioxidant quercetin to improve Dox’s bioavailability and tolerability. The purpose of this study was to characterize the pharmacokinetics and safety of Dox after intravenous (IV) and oral (PO) administration of DoxQ or Dox (10 mg/kg) and investigate the intestinal lymphatic delivery of Dox after PO DoxQ administration in male Sprague–Dawley rats. Drug concentrations in serum, urine, and lymph were quantified by HPLC with fluorescence detection. DoxQ intact IV showed a 5-fold increase in the area under the curve (AUC)—18.6 ± 1.98 compared to 3.97 ± 0.71 μg * h/mL after Dox—and a significant reduction in the volume of distribution (V_ss): 0.138 ± 0.015 versus 6.35 ± 1.06 L/kg. The fraction excreted unchanged in urine (f_e) of IV DoxQ and Dox was ~5% and ~11%, respectively. Cumulative amounts of Dox in the mesenteric lymph fluid after oral DoxQ were twice as high as Dox in a mesenteric lymph duct cannulation rat model. Oral DoxQ increased AUC of Dox by ~1.5-fold compared to after oral Dox. Concentrations of β-N-Acetylglucosaminidase (NAG) but not cardiac troponin (cTnI) were lower after IV DoxQ than Dox. DoxQ altered the pharmacokinetic disposition of Dox, improved its renal safety and oral bioavailability, and is in part transported through intestinal lymphatics.

Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

In the present investigation, an ethanolic fraction (EF) of Lepechinia meyenii (salvia) was prepared and fractionated by gradient column chromatography, and the main secondary metabolites present in the EF were identified by HPLC-MS. Silver nanoparticles (AgNPs) were synthesized and conjugated with the EF of Lepechinia meyenii (salvia). The AgNPs synthesis was optimized using Plackett-Burman design and response surface methodology (RSM), considering the following independent variables: stirring speed, synthesis pH, synthesis time, synthesis temperature and EF volume. The AgNPs synthesized under the optimized conditions were characterized by UV visible spectroscopy (UV-VIS), Fourier Transform Infrared Spectroscopy (FT-IR), Dynamic Light Scattering (DLS) and Scanning Transmission Electron Microscopy (STEM). The antibacterial activity of the AgNPs against Staphylococcus aureus (ATCC^® 25923) was evaluated. The following flavonoids were identified: rosmarinic acid, diosmin and hesperetin-7-O-rutinoside. The optimized conditions for the synthesis of nanoparticles were pH 9.45, temperature 49.8 °C, volume of ethanolic fraction 152.6 µL and a reaction time of 213.2 min. The obtained AgNPs exhibited an average size of 43.71 nm and a resonance plasmon of 410–420 nm. Using FT-IR spectroscopy, the disappearance of the peaks between 626.50 and 1379.54 cm⁻¹ was evident with the AgNPs, which would indicate the participation of these functional groups in the synthesis and protection of the nanoparticles. A hydrodynamic size of 47.6 nm was obtained by DLS, while a size of 40–60 nm was determined by STEM. The synthesized AgNPs conjugated with the EF showed a higher antibacterial activity than the EF alone. These results demonstrate that the AgNPs synthesized under optimized conditions conjugated with the EF of the Lepechinia meyenii (salvia) presented an increased antibacterial activity.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have limited treatment options, particularly if they are transplantation or chimeric antigen receptor (CAR) T-cell ineligible, and novel therapeutics are needed. An 86-year-old woman with relapsed DLBCL received a novel, first-in-class small molecule inhibitor of N-myristoyltransferase (NMT) as the initial patient on a phase I dose escalation trial. Daily oral administration of 20 mg PCLX-001 tablets produced a pharmacokinetic profile suitable for single daily dosing: rapid oral absorption, followed by an apparent elimination half-life of 16 h, without systemic accumulation of drug by day 15. Pharmacodynamic tests showed no clear change in NMT1 and NMT2 levels or selected NMT substrate Lyn and HGAL protein levels in normal circulating blood mononuclear cells, suggesting a higher dose will be required for normal tissue toxicity. The patient did not experience any dose-limiting toxicities but had disease progression after 28 days of study therapy. Dose escalation continues in other patients in this first-in-human study of a new class of anticancer drug. We conclude that PCLX-001 oral monotherapy has suitable pharmacokinetic parameters for dose escalation, and that higher doses are required to achieve pharmacodynamic evidence of on-target activity in normal tissues. The current protocol is appropriately designed to achieve these ends, and the study proceeds without modification.

In the last decade, the green synthesis of nanoparticles has had a prominent role in scientific research for industrial and biomedical applications. In this current study, silver nitrate (AgNO₃) was reduced and stabilized with an aqueous extract of Thelypteris glandulosolanosa (Raqui-raqui), forming silver nanoparticles (AgNPs-RR). UV-vis spectrophotometry, dynamic light scattering (DLS), and scanning transmission electron microscopy (STEM) were utilized to analyze the structures of AgNPs-RR. The results from this analysis showed a characteristic peak at 420 nm and a mean hydrodynamic size equal to 39.16 nm, while the STEM revealed a size distribution of 6.64–51.00 nm with an average diameter of 31.45 nm. Cellular cytotoxicity assays using MCF-7 (ATCC^® HTB-22™, mammary gland breast), A549 (ATCC^® CCL-185, lung epithelial carcinoma), and L929 (ATCC^® CCL-1, subcutaneous connective tissue of Mus musculus) demonstrated over 42.70% of MCF-7, 59.24% of A549, and 8.80% of L929 cells had cell death after 48 h showing that this nanoparticle is more selective to disrupt neoplastic than non-cancerous cells and may be further developed into an effective strategy for breast and lung cancer treatment. These results demonstrate that the nanoparticle surfaces developed are complex, have lower contact angles, and have excellent scratch and wear resistance.

Cannabis sativa is a plant used for recreational and therapeutic purposes; however, many of the secondary metabolites in the plant have not been thoroughly investigated. Stilbenes are a class of compounds with demonstrated anti-inflammatory and antioxidant properties and are present in cannabis. Many stilbenes present in cannabis have been investigated for their therapeutic effects. Fourteen stilbenes have been identified to be present in cannabis, all of which are structurally dihydrostilbenoids, with half possessing a prenylated moiety. The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects. Many of the identified stilbenes have been researched to a limited extent for potential health benefits. In addition, predictive in silico modeling was performed on the fourteen identified cannabis-derived stilbenes. This modeling provides prospective activity, pharmacokinetic, metabolism, and permeability data, setting the groundwork for further investigation into these poorly characterized compounds.