Sorafenib-Loaded PLGA Carriers for Enhanced Drug Delivery and Cellular Uptake in Liver Cancer Cells.

Introduction: Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment. Methods: Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release. Results: PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively. Conclusion: The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.

Fiber Optic Thermo-Hygrometers for Soil Moisture Monitoring.

This work deals with the fabrication, prototyping, and experimental validation of a fiber optic thermo-hygrometer-based soil moisture sensor, useful for rainfall-induced landslide prevention applications. In particular, we recently proposed a new generation of fiber Bragg grating (FBGs)-based soil moisture sensors for irrigation purposes. This device was realized by integrating, inside a customized aluminum protection package, a FBG thermo-hygrometer with a polymer micro-porous membrane. Here, we first verify the limitations, in terms of the volumetric water content (VWC) measuring range, of this first version of the soil moisture sensor for its exploitation in landslide prevention applications. Successively, we present the development, prototyping, and experimental validation of a novel, optimized version of a soil VWC sensor, still based on a FBG thermo-hygrometer, but able to reliably monitor, continuously and in real-time, VWC values up to 37% when buried in the soil.

The c.156_157insAlu BRCA2 rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal.

We evaluated the contribution of an Alu insertion in BRCA2 exon 3 (c.156_157insAlu) to inherited predisposition to breast/ovarian cancer in 208 families originated mostly from northern/central Portugal. We identified the c.156_157insAlu BRCA2 mutation in 14 families and showed that it accounts for more that one-fourth of deleterious BRCA1/BRCA2 mutations in breast/ovarian cancer families originated from this part of the country. This mutation originates BRCA2 exon 3 skipping and we demonstrated its pathogenic effect by showing that the BRCA2 full length transcript is derived only from the wild type allele in carriers, that it is absent in 262 chromosomes from healthy blood donors, and that it co-segregates with the disease. Polymorphic microsatellite markers were used for haplotype analysis in three informative families. In two of the three families one haplotype was shared for all but two markers, whereas in the third family all markers telomeric to BRCA2 differed from that observed in the other two. Although the c.156_157insAlu BRCA2 mutation has so far only been identified in Portuguese breast/ovarian cancer families, screening of this rearrangement in other populations will allow evaluation of whether or not it is a population-specific founder mutation and a more accurate estimation of its distribution and age.