University students' preferences of learning modes post COVID-19-associated lockdowns: In-person, online, and blended.

Online teaching accelerated during COVID-19-associated lockdowns. At that time, it was assumed that university students wanted to revert to in-person sessions at the earliest opportunity. However, when in-person sessions were re-introduced, student attendance was not as high as expected.

Probing milk extracellular vesicles for intestinal delivery of RNA therapies.

Background: Oral delivery remains unattainable for nucleic acid therapies. Many nanoparticle-based drug delivery systems have been investigated for this, but most suffer from poor gut stability, poor mucus diffusion and/or inefficient epithelial uptake. Extracellular vesicles from bovine milk (mEVs) possess desirable characteristics for oral delivery of nucleic acid therapies since they both survive digestion and traverse the intestinal mucosa.

Cow Milk and Intestinal Epithelial Cell-derived Extracellular Vesicles as Systems for Enhancing Oral Drug Delivery.

Ingestion is the preferred way for drug administration. However, many drugs have poor oral bioavailability, warranting the use of injections. Extracellular vesicles (EVs) from cow milk have shown potential utility in improving oral drug bioavailability.

Nanoparticle modification in biological media: implications for oral nanomedicines.

Nanomedicine has shown potential in enabling oral administration of poorly absorbable drugs, such as biologics. As part of the process related to optimisation of the safety and efficacy of nanomedicines, it is imperative that the interaction of nanoparticles with the biological systems - including the gut - is fully characterised. In this article, we provide an overview of the major mechanisms by which nanoparticles may transform upon introduction in biological media.

Delivery of Nanoparticles across the Intestinal Epithelium via the Transferrin Transport Pathway.

The aim of this study was to probe whether the transferrin (Tf) transport pathway can be exploited for intestinal delivery of nanoparticles. Tf was adsorbed on 100 nm model polystyrene nanoparticles (NP), followed by size characterisation of these systems. Cell uptake of Tf and Tf-adsorbed NP was investigated in intestinal epithelial Caco-2 cells cultured on multi-well plates and as differentiated polarised monolayers.

Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics.

Biologics have changed the management of Inflammatory Bowel Disease (IBD), but there are concerns regarding unexpected systemic toxicity and loss of therapeutic response following administration by injection. Local delivery of biologics directly to the inflamed mucosa via rectal enema administration addresses the problems associated with systemic administration. Hydrogels are potentially useful delivery vehicles enabling rectal administration of biologics.

Role of the Basement Membrane as an Intestinal Barrier to Absorption of Macromolecules and Nanoparticles.

Full understanding of the barrier property of mucosal tissues is imperative for development of successful mucosal drug delivery strategies, particularly for biologics and nanomedicines. The contribution of the mucosal basement membrane (BM) to this barrier is currently not fully appreciated. This work examined the role of the BM as a barrier to intestinal absorption of model macromolecules (5 and 10 kDa dextrans) and 100 nm polystyrene nanoparticles.

Ascorbyl Palmitate Hydrogel for Local, Intestinal Delivery of Macromolecules.

Biologics have changed the management of inflammatory bowel disease (IBD), but there are concerns with unexpected systemic toxicity and loss of therapeutic response following administration by injection. Rectal administration of biologics offers potentially reduced therapy costs, as well as safer and more effective local delivery to inflammation sites. Hydrogels are potentially useful carriers of biologics for improved delivery to the inflamed intestinal mucosa.

From Anthramycin to Pyrrolobenzodiazepine (PBD)-Containing Antibody-Drug Conjugates (ADCs).

The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a family of sequence-selective DNA minor-groove binding agents that form a covalent aminal bond between their C11-position and the C2-NH groups of guanine bases. The first example of a PBD monomer, the natural product anthramycin, was discovered in the 1960s, and the best known PBD dimer, SJG-136 (also known as SG2000, NSC 694501 or BN2629), was synthesized in the 1990s and has recently completed Phase II clinical trials in patients with leukaemia and ovarian cancer. More recently, PBD dimer analogues are being attached to tumor-targeting antibodies to create antibody-drug conjugates (ADCs), a number of which are now in clinical trials, with many others in pre-clinical development.

Covalent Bonding of Pyrrolobenzodiazepines (PBDs) to Terminal Guanine Residues within Duplex and Hairpin DNA Fragments.

Pyrrolobenzodiazepines (PBDs) are covalent-binding DNA-interactive agents with growing importance as payloads in Antibody Drug Conjugates (ADCs). Until now, PBDs were thought to covalently bond to C2-NH2 groups of guanines in the DNA-minor groove across a three-base-pair recognition sequence. Using HPLC/MS methodology with designed hairpin and duplex oligonucleotides, we have now demonstrated that the PBD Dimer SJG-136 and the C8-conjugated PBD Monomer GWL-78 can covalently bond to a terminal guanine of DNA, with the PBD skeleton spanning only two base pairs.

Crispene E, a cis-clerodane diterpene inhibits STAT3 dimerization in breast cancer cells.

Crispene E, a new clerodane-type diterpene, inhibited STAT3 dimerization in a cell-free fluorescent polarisation assay and was found to have significant toxicity against STAT3-dependent MDA-MB 231 breast cancer cell line and selectively inhibited the expression of STAT3 and STAT3 target genes cyclin D1, Fascin and bcl-2. Molecular docking studies suggest the molecule inhibits STAT3 by interacting with its SH2 domain. The compound has been isolated from Tinospora crispa and characterized using standard spectroscopic techniques.