Glutaraldehyde-crosslinking chitosan scaffolds reinforced with calcium phosphate spray-dried granules for bone tissue applications.

The clinical demand for bone scaffolds as an alternative strategy for bone grafting has increased exponentially and, up to date, numerous formulations have been proposed to regenerate the bone tissue. However, most of these structures lack at least one of the fundamental/ideal properties of these materials (e.g., mechanical resistance, interconnected porosity, bioactivity, biodegradability, etc.). In this work, we developed innovative composite scaffolds, based on crosslinked chitosan with glutaraldehyde (GA), combined with different atomized calcium phosphates (CaP) granules - hydroxyapatite (HA) or biphasic mixtures of HA and ß - tricalcium phosphate (ß-TCP), with improved biomechanical behavior and enhanced biological response. This innovative combination was designed to improve the scaffolds' functionality, in which GA improved chitosan mechanical strength and stability, whereas CaP granules enhanced the scaffolds' bioactivity and osteoblastic response, further reinforcing the scaffolds' structure. The biological assessment of the composite scaffolds showed that the specimens with 0.2% crosslinking were the ones with the best biological performance. In addition, the inclusion of biphasic granules induced a trend for increase osteogenic activation, as compared to the addition of HA granules. In conclusion, scaffolds produced in the present work, both with HA granules or the biphasic ones, and with low concentrations of GA, have shown adequate properties and enhanced biological performance, being potential candidates for application in bone tissue engineering.

Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity.

In spite of recent efforts to eradicate malaria in the world, this parasitic disease is still considered a major public health problem, with a total of 216 million cases of malaria and 445,000 deaths in 2016. Artemisinin-based combination therapies remain effective in most parts of the world, but recent cases of resistance in Southeast Asia have urged for novel approaches to treat malaria caused by Plasmodium falciparum. In this work, we present chloroquine analogs that exhibited high activity against sensitive and chloroquine-resistant P. falciparum blood parasites and were also active against P. berghei infected mice. Among the compounds tested, DAQ, a chloroquine analog with a more linear side chain, was shown to be the most active in vitro and in vivo, with low cytotoxicity, and therefore may serve as the basis for the development of more effective chloroquine analogs to aid malaria eradication.