João Pedro Martins

Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients (P_app) of 2.37 × 10⁻⁶ cm/s, over the 1.66 × 10⁻⁶ cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.

Here, a continuous two-step glass-capillary microfluidic technique to produce a multistage oral insulin delivery system is reported. This system represents a promising alternative for the common protein/peptide-loaded liposome formulations.

This commentary article conveys the views of the board of the Nanomedicine and Nanoscale Delivery Focus Group of the Controlled Release Society regarding the decision of the United States National Cancer Institute (NCI) in halting funding for the Centers of Cancer Nanotechnology Excellence (CCNEs), and the subsequent editorial articles that broadened this discussion.

The advent of nanomedicine has recently started to innovate the treatment of cardiovascular diseases, in particular myocardial infarction. Although current approaches are very promising, there is still an urgent need for advanced targeting strategies. In this work, the exploitation of macrophage recruitment is proposed as a novel and synergistic approach to improve the addressability of the infarcted myocardium achieved by current peptide-based heart targeting strategies. For this purpose, an acetalated dextran-based nanosystem is designed and successfully functionalized with two different peptides, atrial natriuretic peptide (ANP) and linTT1, which target, respectively, cardiac cells and macrophages associated with atherosclerotic plaques. The biocompatibility of the nanocarrier is screened on both macrophage cell lines and primary macrophages, showing high safety, in particular after functionalization of the nanoparticles’ surface. Furthermore, the system shows higher association versus uptake ratio towards M2-like macrophages (approximately 2-fold and 6-fold increase in murine and human primary M2-like macrophages, respectively, compared to M1-like). Overall, the results demonstrate that the nanosystem has potential to exploit the “hitchhike” effect on M2-like macrophages and potentially improve, in a dual targeting strategy, the ability of the ANP peptide to target infarcted heart.

Juvenile delinquency is a universal problem, with serious personal, economic, and social consequences that span national boundaries. Thus, cross-culturally valid and reliable measures of delinquency are critical to providing a better understanding of the causes, correlates, and outcomes of delinquency. The main aim of the present study was to examine the psychometric properties of a Portuguese version of the self-report delinquency measure items created for the National Longitudinal Study of Adolescent Health (Add Health). A sample (N = 412) of male (n = 200) and female (n = 212) at-risk for delinquency youths agreed to participate in the present study. The measure demonstrated satisfactory psychometric properties, namely in terms of its two-factor structure (violent and nonviolent delinquency), internal consistency, convergent validity, discriminant validity, criterion-related validity, and known-groups validity. Findings suggest the Add Health Self-Report Delinquency (AHSRD) is an interculturally valid and reliable measure of violent and nonviolent delinquency among at-risk male and female youths.

Nanotechnology holds the promise of bringing revolutionary therapeutic strategies into the clinic. However, an enormous fraction of the currently proposed nanotechnology‐based therapies suffers from lack of reproducibility, complexity, high costs, and scale‐up‐related issues. For these reasons, the research community is moving toward the miniaturization of biomaterials and fabrication methods. Customizable microfluidic‐based products have gained tremendous relevance in the development of biomedical technologies. This review provides an overview of different materials that can be used for the fabrication of microfluidic devices, as well as the other parameters influencing the production of biomaterials and biosensors. Moreover, several advanced microfluidic‐based technologies that are designed to overcome the current challenges of cancer, immunotherapy, and diabetes therapy, among others are described. Then, the pros and cons of microfluidics as alternative to conventional preparation methods, and the challenges of translating this technique to an industrial context are highlighted. Overall, microfluidic technologies and their accessibility to the research community offer a set of exciting opportunities to bridge the development of innovative therapies and their commercialization in the foreseeable future.