The advent of nanomedicine providing therapeutic options of refined performance continues. Although PEGylation as a tool to improve the pharmacokinetics of nanomedicines is well established and is used clinically, other benefits of 'PEGnology', including enhancement of physicochemical properties and/or biocompatibility of actives and/or drug carriers, as well as mucosal delivery, have attracted less attention. While concerns regarding the clinical use of PEGylated nanomedicines remain, evidence suggests that at least some safety issues may be controlled by adequate designs of nanosystems.

Ball oder Röhre: Flexible und amorphe Nanoröhren bilden sich aus einem Palladiumsalz und einem mehrzähnigen Liganden mit tetraedrischer Struktur (rechts). Dagegen führen Liganden mit zweidimensionaler Geometrie unabhängig von der Zahl der Metallkoordinationsstellen zur Bildung von Kugeln und deren Aggregaten (links).

No abstract

Research into oral delivery of biologics has a long and rich history but has not produced technologies used in the clinic. The area has evolved in terms of strategies to promote oral biologics delivery from early chemical absorption enhancers to nanomedicine to devices. Continued activity in this area is justifiable considering the remarkable proliferation of biologics. Areas covered: The article discusses some physiological barriers to oral delivery of biologics, with a special focus on less characterized barriers such as the basement membrane. Recent progress in oral delivery of biologics via nanomedicine is subsequently covered. Finally, the emerging field of device-mediated gastrointestinal delivery of biotherapeutics is discussed. Expert opinion: Oral delivery of biologics is considered a 'panacea' in drug delivery. Almost century-old approaches of utilizing chemical absorption enhancers have not produced clinically translated technologies. Nanomedicine for oral biologics delivery has demonstrated potential, but the field is relatively new, and technologies have not progressed to the clinic. Device-mediated oral biologics delivery (e.g. ultrasound or microneedles) is in its infancy. However, this space is likely to intensify owing to advances in electronics and materials, as well as the challenges and history related to clinical translation of alternative approaches.

Non-invasive delivery of biotherapeutics, as an attractive alternative to injections, could potentially be achieved through the mucosal surfaces, utilizing nanoscale therapeutic carriers. However, nanoparticles do not readily cross the mucosal barriers, with the epithelium presenting a major barrier to their translocation. The transcytotic pathway of vitamin B12 has previously been shown to ‘ferry’ B12-decorated nanoparticles across intestinal epithelial (Caco-2) cells. However, such studies have not been reported for the airway epithelium. Furthermore, the presence in the airways of the cell machinery responsible for transepithelial trafficking of B12 is not widely reported. Using a combination of molecular biology and immunostaining techniques, our work demonstrates that the bronchial cell line, Calu-3, expresses the B12-intrinsic factor receptor, the transcobalamin II receptor and the transcobalamin II carrier protein. Importantly, the work showed that sub-200 nm model nanoparticles chemically conjugated to B12 were internalised and transported across the Calu-3 cell layers, with B12 conjugation not only enhancing cell uptake and transepithelial transport, but also influencing intracellular trafficking. Our work therefore demonstrates that the B12 endocytotic apparatus is not only present in this airway model, but also transports ligand-conjugated nanoparticles across polarised epithelial cells, indicating potential for B12-mediated delivery of nanoscale carriers of biotherapeutics across the airways.