Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 μm and from 0.641 to 0.796 μm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.
The aim of the present study was to investigate the potential application of 3,6-O,O'- dimyristoyl chitosan DMCh, an amphiphilic derivative of chitosan, for improving the oral bioavailability of paclitaxel (PTX), a water insoluble anticancer drug. The O-acylation of chitosan with myristoyl chloride was carried out by employing high (≈13.3) or low (2.0) molar excess of chitosan to result in samples DMCh07 and DMCh12, respectively. The successful O-acylation of chitosan was confirmed by FTIR and H NMR spectroscopy, the latter allowing also the determination of average degree of substitution (DS). The critical aggregation concentration (CAC) of samples DMCh07 (DS≈6.8%) and DMCh12 (DS≈12.0%) were 8.9×10mg/mL and 13.2×10mg/mL, respectively. It was observed by TEM that the DMCh micelles showed spherical shape while DLS measurements allowed the determination of their average size (287nm-490nm) and zeta potential (+32mV to +44mV). Such DMCh micelles were able to encapsulate paclitaxel with high drug encapsulation efficiency (EE), as confirmed by HPLC analyses. Studies on the cytotoxicity of DMCh07 micelles toward Caco-2 and HT29-MTX cells showed that, regardless the PTX loaded, DMCh07 micelles slightly decreased cellular viability at low micelles concentration (≤1μg/mL) while at high concentration (>10μg/mL) PTX-loaded DMCh07 micelles were less toxic toward Caco-2 cells when compared to free PTX. The PTX permeation across Caco-2 monoculture and Caco-2/HT29-MTX co-culture model confirmed the potential of DMCh micelles in improving the intestinal absorption of PTX. These results suggest that DMCh micelles may be a promising carrier to encapsulate PTX aiming cancer therapy.
High amylose and pectin were mixed at 1:1 mass ratio and cross-linked with sodium trimetaphosphate (STMP) in alkaline medium. Films were prepared from aqueous dispersions of these cross-linked polymer blend at three different concentrations (3, 4 and 5%), by solvent casting method. Characterization of the films included thickness, surface morphology, water uptake, water vapor permeability (WVP), tensile strength measurements and enzymatic digestion. The cross-linking allowed to obtain films with improved mechanical properties and reduced WVP. The high resistance to enzymatic digestion exhibited by these films represents a promising approach to their application in the development of colon drug delivery systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.