Paclitaxel (PTX) is one of the most potent intravenous chemotherapeutic agents to date, yet an oral formulation has been problematic because of its low solubility and permeability. Using the recently discovered solubilizing properties of rubusoside (RUB), we investigated the unique PTX–RUB formulation. PTX was solubilized by RUB in water to levels of 1.6–6.3 mg/ml at 10–40% weight/volume. These nanomicellar PTX–RUB complexes were dried to a powder, which was subsequently reconstituted in physiologic solutions. After 2.5 h, 85–99% of PTX–RUB remained soluble in gastric fluid, whereas 79–96% remained soluble in intestinal fluid. The solubilization of PTX was mechanized by the formation of water-soluble spherical nanomicelles between PTX and RUB, with an average diameter of 6.6 nm. Compared with Taxol, PTX–RUB nanoparticles were nearly four times more permeable in Caco-2 cell monocultures. In a side-by-side comparison with dimethyl sulfoxide-solubilized PTX, PTX–RUB maintained the same level of cytotoxicity against three human cancer cell lines with IC₅₀ values ranging from 4 to 20 nmol/l. In addition, tubule formation and migration of human umbilical vein endothelial cells were inhibited at levels as low as 5 nmol/l. These chemical and biological properties demonstrated by the PTX–RUB nanoparticles may improve oral bioavailability and enable further pharmacokinetic, toxicologic, and efficacy investigations.

Paclitaxel, which features low water solubility and permeability, is an efflux pump substrate. The current paclitaxel drugs are given intravenously after resolving the solubility issue. Yet, oral delivery to achieve therapeutic bioavailability is not effective due to low absorption. This study evaluated a natural compound, rubusoside, to improve oral bioavailability in an animal model. Free paclitaxel molecules were processed into nano-micelles formed in water with rubusoside. The particle size of the nano-micelles in water was determined using dynamic light scattering. The oral bioavailability of paclitaxel in nano-micelles was determined against Cremophor/alcohol-solubilized Taxol after oral and intravenous administration to pre-cannulated Sprague Dawley rats. When loaded into the rubusoside-formed nano-micelles, paclitaxel reached a supersaturated concentration of 6 mg/mL, 60,000-fold over its intrinsic saturation of 0.1 µg/mL. The mean particle size was 4.7 ± 0.7 nm in diameter. Compared with Taxol^®, maximum blood concentration was increased by 1.5-fold; the time to reach maximum concentration shortened to 0.8 h from 1.7 h; and, relative oral bioavailability increased by 88%. Absolute oral bioavailability was 1.7% and 1.3% for the paclitaxel nano-micelles and Taxol^®, respectively. Solubilizing paclitaxel with rubusoside was successful, but oral bioavailability remained low. Further inhibition of the efflux pump and/or first metabolism may allow more oral paclitaxel to enter systemic circulation.

Background: Safe and efficient disposal of millions of tons of pepper sauce waste (PSW) can be a challenge to pepper sauce manufacturers that are concerned about creating environmental hazards from the processing (e.g., preservative salt and vinegar) and intrinsic (e.g., the pungent capsaicins) ingredients. It will be immensely beneficial to process these waste materials before they go to disposal. This work presents integrated approaches for a complete utilization of waste materials by removing and recovering valuable by-products and/or ingredients while succeeding to minimal to zero hazards. Methods: Laboratory- and pilot-scale extraction processes were used to demonstrate the recovery of intrinsic compounds from PSW to pungent pepper oil. Flash chromatography was then applied to isolate the pungent capsaicins out of the pepper oil, thus generating a no-heat pepper oil. Results: By processing the waste materials, a number of valuable by-products with various yield percentages were produced. They included (1) hot red pepper oil (RPO, 8.0% v/w), (2) no-heat pepper residue (NHPR, 25.3% w/w), (3) no-heat red pepper oil (NHRPO, 4.0% v/w), (4) capsaicinoids (0.8% w/w), and (5) capsaicin (0.4% w/w). The optimum processing conditions for products 1, 2, and 3 include extracting the waste materials with 95% ethanol twice, each lasting three hours. The optimal isolation conditions of flash column chromatography to obtain products 4 and 5 include the use of the pre-packed chromatography column 130 g Redisep C18, preparing the sample concentration to 100 mg/mL, eluting with aqueous ethanol, and detecting capsaicins at a wavelength of 228 nm. Conclusions: An integrated approach is offered for the complete utilization of PSW. It not only turns organic food waste into numerous new commodities but also significantly reduces the volume and degree of potential environmental hazard to the disposal sites.

Although previous research showed that the purple symptom of Cercospora leaf blight (CLB) is associated with lower biomass of Cercospora cf. flagellaris and lower concentrations of cercosporin, a reactive oxygen species producer, as compared with blighted leaves, the hypothesis that the purple symptom is a plant reaction to the pathogen has never been tested. In this study, we demonstrated that high levels of coumestrol (COU) were associated with purple symptoms of CLB and that COU has strong antioxidant activity. Additionally, we found that COU is restricted to the pigmented areas of purple leaves, and the pigmentation is restricted to the adaxial surfaces, suggesting that COU may be acting as a sunscreen. Even though COU is associated with the purple leaf symptom, this coumestan is not the direct cause of discoloration in that COU is colorless. Quantification of chlorophyll a and b and total carotenoids suggested that blighted but not purple or asymptomatic leaves were undergoing photooxidative stress. Because the purple symptom is associated with high COU concentrations, lower biomass of C. cf. flagellaris, and lower cercosporin concentrations, we conclude that the purple symptom is a disease resistance reaction, mediated in part by COU, which provides a high level of antioxidant activity and, hence, partial resistance.

Ball moss is an epiphytic, perennial monocot that attaches to many surfaces, including ornamental plants. Though not parasitic, ball moss can reduce the growth and health of host plants. Controlling ball moss has thus become necessary. Recommended methods include spraying baking soda or copper fungicide. This study was designed to validate the recommended methods and discover new, efficacious botanical ingredients in laboratory and field experiments. The efficacy of baking soda, but not the copper fungicide, was confirmed. However, baking soda blindly damages host plants and is not environmentally friendly. A screening study over several candidates (a monocot herbicide, eugenol, thymol, oleander extracts) selected eugenol from clove essential oil. In repeated laboratory studies, eugenol formulated into a soluble liquid (ESL) at 1% concentration achieved comparable lethal levels to 50% baking soda solution against ball moss. Efficacy was most apparent when applied in autumn. In the field trials, spraying ESL directly onto ball moss on live oak trees rather than broadcasting from the ground was efficacious. Possible mechanisms and limitations were discussed.