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To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs. [Display omitted] • Galactosylated prodrug and polymeric solid dispersion strategies were applied. • Combined drug delivery strategies reduced the ulcerogenicity of mefenamic acid. • By applying two approaches, the biological activity of mefenamic acid was extended. • The concomitant use of two strategies boosted the cytotoxicity of mefenamic acid. [ABSTRACT FROM AUTHOR]

• Improved sustainability ROP of LA using terpene initiators in the biorenewable solvent 2-MeTHF. • Small Library of terpene-alcohols was used as initiators in the generation of PDLLA oligomers. • Oligomers self-assembled in water to form well-defined NPs without the use of stabilisers. • NPs were found to be biocompatible when tested on lung, intestinal and skin cells. In this work we aimed to achieve a totally sustainable Ring Opening Polymerisation (ROP) process, by harmonising the use of naturally occurring or derivable initiators and the green solvent 2-Methyltetrahydrofuran (2-MeTHF). First, a library of novel monoterpene-alcohols and existing terpenoids was used to provide renewably sourced initiators for a metal-free ROP synthetic step. A number of these initiators are derived from waste materials, further improving their sustainability. Secondly, we selected lactide (LA) as a monomer, because not only is it derived from biomass, but its resultant polymers are biocompatible and biodegradable. Interestingly, these new polymers self-assembled in water producing well defined, biocompatible nanoparticles (NPs) via direct nanoprecipitation without the use of additional stabilisers. We have highlighted a novel and promising (ROP) approach to produce biodegradable, amphiphilic ester-based macromolecules, based on lactide and terpenes (as initiators) in a green solvent, 2-MeTHF thus reducing solvent toxicity in an efficient, simple and sustainable new synthesis. The monoterpenes may provide a highly functionalisable and bio-renewable toolbox for a new generation of ROP initiators. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the linkage between the quality of the learning environment and the quality of students' experience in seven high school classrooms in six different subject areas. The quality of the learning environment was conceptualized in terms of environmental complexity, or the simultaneous presence of environmental challenge and environmental support. The students ( N = 108) in each class participated in the Experience Sampling Method (ESM) measuring their engagement and related experiential variables. Concurrently, environmental complexity and its subdimensions were observed and rated from video with a new observational instrument, The Optimal Learning Environments – Observational Log and Assessment (OLE-OLA). Using two-level HLM regression models, ratings from the OLE-OLA were utilized to predict student engagement and experiential variables as measured by the ESM. Results showed that environmental complexity predicted student engagement and sense of classroom self-esteem. Implications for research, theory and practice are discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] Laurate (C 12)-sucrose esters are established intestinal epithelial permeation enhancers (PEs) with potential for use in oral delivery. Most studies have examined blends of ester rather than specific monoesters, with little variation on the sugar moiety. To investigate the influence of varying the sugar moiety on monoester performance, we compared three monoesters: C 12 -sucrose, C 12 -lactose, and C 12 -trehalose. The assays were: critical micellar concentration (CMC) in Krebs-Henseleit buffer, MTS and lactate dehydrogenase assays in Caco-2 cells, transepithelial electrical resistance (TEER) and apparent permeability coefficient (P app) of 14C] mannitol across isolated rat intestinal mucosae, and tissue histology. For CMC, the rank order was C 12 -trehalose (0.21 mM) < C 12 -sucrose (0.34 mM) < C 12 -lactose (0.43 mM). Exposure to Caco-2 cells for 120 min produced TC 50 values in the MTS assay from 0.1 to 0.4 mM. Each ester produced a concentration-dependent decrease in TEER across rat mucosae with 80% reduction seen with 8 mM in 5 min, but C 12 -trehalose was less potent. C 12 -sucrose and C 12 -lactose increased the P app of 14C] mannitol across mucosae with similar potency and efficacy, whereas C 12 -trehalose was not as potent or efficacious, even though it still increased flux. In the presence of the three esters, gross intestinal histology was unaffected except at 8 mM for C 12 -sucrose and C 12 -lactose. In conclusion, the three esters enhanced permeability likely via tight junction modulation in rat intestinal tissue. C 12 -trehalose was not quite as efficacious, but neither did it damage tissue to the same extent. All three can be considered as potential PEs to be included in oral formulations. [ABSTRACT FROM AUTHOR]