Chitosan Hydrogels for Synergistic Delivery of Chemotherapeutics to Triple Negative Breast Cancer Cells and Spheroids.

PURPOSE: This study aimed to develop a hydrogel system for treating aggressive triple negative breast cancer (TNBC) via kinetically-controlled delivery of the synergistic drug pair doxorubicin (DOX) and gemcitabine (GEM). A 2D assay was adopted to evaluate therapeutic efficacy by determining combination index (CI), and a 3D assay using cancer spheroids was implemented to assess the potential for translation in vivo. METHODS: The release of DOX and GEM from an acetylated-chitosan (ACS, degree of acetylation χAc = 40 ± 5%) was characterized to identify a combined drug loading that affords release kinetics and dose that are therapeutically synergistic. The selected DOX/GEM-ACS formulation was evaluated in vitro with 2-D and 3-D models of TNBC to determine the combination index (CI) and the tumor volume reduction, respectively. RESULTS: Therapeutically desired release dosages and kinetics of GEM and DOX were achieved. When evaluated with a 2-D model of TNBC, the hydrogel afforded a CI of 0.14, indicating a stronger synergism than concurrent administration of DOX and GEM (CI = 0.23). Finally, the therapeutic hydrogel accomplished a notable volume reduction of the cancer spheroids (up to 30%), whereas the corresponding dosages of free drugs only reduced growth rate. CONCLUSIONS: The ACS hydrogel delivery system accomplishes drug release kinetics and molar ratio that affords strong therapeutically synergism. These results, in combination with the choice of ACS as affordable and highly abundant source material, provide a strong pre-clinical demonstration of the potential of the proposed system for complementing surgical resection of aggressive solid tumors.

Xyloglucan from Hymenaea courbaril var. courbaril seeds as encapsulating agent of l-ascorbic acid.

This study evaluated the l-ascorbic acid (AA) encapsulation in microparticles of xyloglucan (XAA) extracted from Hymenaea courbaril seeds by spray drying (SD) and its application in tilapia fish burgers. The encapsulation efficiency was 96.34±1.6% and the retention of the antioxidant activity was of 89.48±0.88% after 60days at 25°C. SEM images showed microspheres with diameters ranging from 4.4 to 34.0µm. FTIR spectrum confirmed the presence of AA in xyloglucan microparticles, which was corroborated by DSC and TGA. The release of ascorbic acid was found to be pH-dependent. The application of XAA in tilapia fish burger did not change the pH after heating and the ascorbic acid retention was greater compared to its free form. The results indicate that xyloglucan can be used to encapsulate AA by SD and suggest that XAA was able to reduce undesirable organoleptic changes in fish burgers.

Isolation of a lectin and a galactoxyloglucan from Mucuna sloanei seeds.

A lectin and a galactoxyloglucan were characterized from Mucuna sloanei seed cotyledons. The galactoxyloglucan, isolated by water extraction and ethanol precipitation, had Glc:Xyl:Gal proportions in a molar ratio of 1.8:1.7:1.0 and a molar mass (M(w)) of 1.6x10(6)g mol(-1). The lectin (sloanin), isolated from the same seed by affinity chromatography on cross-linked Adenanthera pavonina galactomannan, gave two protein bands by SDS-PAGE (36 and 34 kDa) and one peak by gel filtration (63.6 kDa). Its N-terminal sequence indicated approximately 69% identity with soybean agglutinin to leguminous lectins. Circular dichroism (CD) spectra established that sloanin predominantly contains beta-sheet structures. Sloanin has approximately 5.5% carbohydrate and displayed hemagglutinating activity against rabbit and enzyme treated human erythrocytes, inhibited only by D-Gal containing sugars. The interaction between sloanin and storage cell-wall galactoxyloglucan was tested by affinity chromatography and fluorescence spectroscopy.