Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy.

Anti-vascular endothelial growth factor (anti-VEGF) therapy applied to solid tumors is a promising strategy, yet, the challenge to deliver these agents at high drug concentrations together with the maintenance of therapeutic doses locally, at the tumor site, minimizes its benefits. To overcome these obstacles, we propose the development of a bevacizumab-loaded alginate hydrogel by electrostatic interactions to design a delivery system for controlled and anti-angiogenic therapy under tumor microenvironmental conditions. The tridimensional hydrogel structure produced provides drug stability and a system able to be introduced as a flowable solution, stablishing a depot after local administration. Biological performance by the chick embryo chorioallantoic membrane (CAM) assay indicated a pH-independent improved anti-angiogenic activity (∼50%) compared to commercial available anti-VEGF drug. Moreover, there was a considerable regression in tumor size when treated with this system. Immunohistochemistry highlighted a reduced number and disorganization of microscopic blood vessels resulting from applied therapy. These results suggest that the developed hydrogel is a promising approach to create an innovative delivery system that offers the possibility to treat different solid tumors by intratumoral administration.

Browplasminin, a condensed tannin with anti-plasmin activity isolated from an aqueous extract of Brownea grandiceps Jacq. flowers.

ETHNOPHARMACOLOGICAL RELEVANCE: Following Venezuelan traditional medicine, females with heavy menstrual blood loss (menorrhagia) drink Brownea grandiceps Jacq. flowers (BG) decoctions to reduce the bleeding. In a previous study, we demonstrated that BG aqueous extract (E) possesses a potent anti-fibrinolytic activity capable of inhibiting plasmin, the main serine-protease that degrades fibrin. It is widely known that plasmin inhibitors are often used as anti-fibrinolytics to reduce bleeding during surgeries with high risk of blood loss such as cardiac, liver, vascular, tooth extraction and large orthopedic procedures, as well as for menorrhagia treatments. The aim of this work was to isolate and characterize from BGE the compound responsible for the reported anti-fibrinolytic activity. MATERIALS AND METHODS: A decoction of BG was prepared; then it was homogenized, centrifuged and lyophilized to obtain BGE. Subsequently the extract was fractionated by gel filtration and reverse phase using HPLC and the active compound was characterized by MALDI-ToF MS. The kinetic parameters of anti-plasmin activity were evaluated by an amidolytic assay using a chromogenic substrate; also the anti-plasmin activity was estimated by fibrin plate method. Data were analyzed by nonparametric statistics. RESULTS: The active compound was a condensed tannin denominated Browplasminin, which is capable of inhibiting the plasmin activity in a dose-dependent manner when measured in fibrin plates or by the amidolytic activity method; it also has a minor effect on the FXa activity. However, it does not affect the activity of other serine-proteases such as trypsin, t-PA or u-PA. Browplasminin consists predominately of heteroflavan-3-ols of catechin with B-type linkages, and extents up to heptadecamers (~ 5000Da), with hexose residues attached to the polymer that presents a high degree of galloylation. Its IC50 for plasmin was 47.80µg/mL and for FXa was 237.08µg/mL, while the Ki were 0.76 and 61.61µg/mL for plasmin and FXa, respectively. CONCLUSIONS: The overall outcome of this study suggests that Browplasminin could be responsible for reducing heavy menstrual bleeding in women because its kinetic parameters showed that is a good plasmin inhibitor.

Orange waste: A valuable carbohydrate source for the development of beads with enhanced adsorption properties for cationic dyes.

Eco-friendly pectin and pectin/cellulose microfibers beads (PB and PB-CF) were synthesized using compounds extracted from orange bagasse, a solid waste from the food industry. PB-CF beads showed remarkable differences regarding several properties as compared to the beads without CF. The adsorption capability of PB and PB-CF was tested towards the removal of methylene blue (MB) from aqueous solution. The effect of various parameters on the MB adsorption was investigated. The kinetics and mechanism of adsorption were explained by the pseudo-second-order kinetics and intra-particle diffusion models. Equilibrium adsorption data are explained by the Langmuir isotherm model, which revealed a maximum adsorption capacity of 1550.3mg/g for PB and 2307.9mg/g for PB-CF5. Thermodynamic analysis suggests that the adsorption of MB on the beads is spontaneous and favorable. Recycling study demonstrated that both PB and PB-CF5 can be implemented in 6 consecutive adsorption/desorption cycles without losing their adsorption capacity. These results enable the use of PB and PB-CF as potentially low-cost adsorbents for wastewater treatments.

Chitosan/poly(vinyl alcohol)/bovine bone powder biocomposites: A potential biomaterial for the treatment of atopic dermatitis-like skin lesions.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects a large percent of the world́s population. This long-lasting skin disease has been treated by different approaches according to its causative agent and severity. Nonetheless, the use of advanced biomaterials to treat AD is poorly explored. The present study assessed the protective effectiveness of biocomposites films based on chitosan (Cs), poly(vinyl alcohol) (PVA) and bovine bone powder (BBP) on AD-like skin lesions. These original biocomposites were fully characterized and in vivo biological assays concerning the AD treatment were performed using a mouse model induced by 2,4-dinitrochlorobenzene (DNCB). The dorsal skin and ear of Balb/c female mice were challenging cutaneously with DNCB. Our findings demonstrate BBP-based biocomposite attenuated and treated considerably the DNCB-induced skin lesions in an AD-like model. In this sense, this study suggests that this original biocomposite may be applied as an active biomaterial for AD treatment.