The blood-brain barrier and beyond: Nano-based neuropharmacology and the role of extracellular matrix.

Restrained drug delivery due to the blood-brain barrier (BBB) considerably limits options for the treatment of brain pathologies. The utilization of nanoparticulate (NP) carriers has been proposed as a solution. The development strategies need to address the important hurdle of NP passage across the BBB as well as the altered cellular up-take due to the pathophysiological changes of the damaged or diseased tissue as well as immunological and toxicological aspects of nanomedicine penetration. This review therefore scopes to: 1) outline the state-of-the art knowledge on BBB passage, 2) address the significant influence of pathological conditions on nanoparticulate drug delivery, and, 3) highlight the largely neglected role of the extracellular matrix (ECM). Interactions of the nanosystem with biological barriers, cells and ECM in the milieu of brain pathologies are critically discussed in order to present a holistic overview of the advances and pits of nanomedicine applications in brain disease.

COVID-19 vaccines: ethical framework concerning human challenge studies.

BACKGROUND: The pandemic associated with the new SARS-CoV-2 coronavirus continues to spread worldwide. The most favorable epidemic control scenario, which provides long-term protection against COVID-19 outbreak, is the development and distribution of an effective and safe vaccine. The need to develop a new COVID-19 vaccine is pressing; however, it is likely to take a long time, possibly several years. This is due to the time required to demonstrate the safety and efficacy of the proposed vaccine. and the time required to manufacture and distribute millions of doses. OBJECTIVES: To accelerate this development and associated safety testing, the deliberate infection of healthy volunteers has been suggested. The purpose of this short communication is to describe the ethical aspects of this type of testing, RESULTS: Deliberate infection of volunteers with a dangerous virus such as SARS-CoV-2 was initially considered unethical by researchers; but the current pandemic is so different from previous ones that these studies are considered ethical if certain criteria are met. Participants in human challenge studies must be relatively young, in good health and must receive the highest quality medical care, with frequent monitoring. Tests should also be performed with great caution and specialized medical supervision. Besides, the fact that obtaining vaccines faster through deliberate infection studies of healthy people has greater benefits than risks, has been demonstrated by obtaining other vaccines in other historical pandemics such as: smallpox, influenza, malaria, typhoid fever, Dengue fever and Zika. CONCLUSIONS: One possibility to shorten the time required for the development of COVID-19 vaccines is to reduce clinical phases II and III by using human challenge studies through eliberate infection of healthy volunteers with SARS-CoV-2 after administration of the candidate vaccine. Accelerating the development of a COVID-19 vaccine even for a few weeks or months would have a great beneficial impact on public health by saving many lives.

Towards effective COVID­19 vaccines: Updates, perspectives and challenges (Review).

In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS­COV­2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID­19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

The Cytotoxic Effects of Betulin-Conjugated Gold Nanoparticles as Stable Formulations in Normal and Melanoma Cells.

Gold nanoparticles are currently investigated as theranostics tools in cancer therapy due to their proper biocompatibility and increased efficacy related to the ease to customize the surface properties and to conjugate other molecules. Betulin, [lup-20(29)-ene-3ß, 28-diol], is a pentacyclic triterpene that has raised scientific interest due to its antiproliferative effect on several cancer types. Herein we described the synthesis of surface modified betulin-conjugated gold nanoparticles using a slightly modified Turkevich method. Transmission electron microscopy (TEM) imaging, dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used for the characterization of obtained gold nanoparticles. Cytotoxic activity and apoptosis assessment were carried out using the MTT and Annexin V/PI apoptosis assays. The in vitro results showed that betulin coated gold nanoparticles presented a dose-dependent cytotoxic effect and induced apoptosis in all tested cell lines.

Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for tissue engineering: Preparation and in vitro evaluation.

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample.