Brain Gene Silencing with Cationic Amino-Capped Poly(ethylene glycol) Polyplexes.

Therapeutic gene silencing in the brain is usually achieved using highly invasive intracranial administration methods and/or comparatively toxic vectors. In this work, we use a relatively biocompatible vector: poly(ethylene glycol) star-shaped polymer capped with amine groups (4APPA) via the nose to brain route. 4APPA complexes anti- itchy E3 ubiquitin protein ligase (anti-ITCH) siRNA to form positively charged (zeta potential +15 ± 5 mV) 150 nm nanoparticles. The siRNA-4APPA polyplexes demonstrated low cellular toxicity (IC50 = 13.92 ± 6 mg mL-1) in the A431 cell line and were three orders of magnitude less toxic than Lipofectamine 2000 (IC50 = 0.033 ± 0.04 mg mL-1) in this cell line. Cell association and uptake of fluorescently labelled siRNA bound to siRNA-4APPA nanoparticles was demonstrated using fluorescent activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM), respectively. Gene silencing of the ITCH gene was observed in vitro in the A431 cell line (65% down regulation when compared to the use of anti-ITCH siRNA alone). On intranasal dosing with fluorescently labelled siRNA-4APPA polyplexes, fluorescence was seen in the cells of the olfactory bulb, cerebral cortex and mid-brain regions. Finally, down regulation of ITCH was seen in the brain cells (54 ± 13% ITCH remaining compared to untreated controls) in a healthy rat model, following intranasal dosing of siRNA-4APPA nanoparticles (0.15 mg kg-1 siRNA twice daily for 3 days). Gene silencing in the brain may be achieved by intranasal administration of siRNA- poly(ethylene glycol) based polyplexes.

Cassava and banana starch modified with maleic anhydride-poly (ethylene glycol) methyl ether (Ma-mPEG): A comparative study of their physicochemical properties as coatings.

This study proposes a simple route to obtain starch grafted copolymers from cassava and banana starches chemically modified with amphiphilic maleic anhydride-poly (ethylene glycol) methyl ether (Ma-mPEG). The starches were extracted from cassava (StC) and banana (StB) pulp and characterized by FTIR spectroscopy, amylose content, scanning electron microscope (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and average molecular weight. Starches were chemically modified with amphiphilic Ma-mPEG in three mass ratios 1:1, 1:2 and 1:3. Thermal behavior and interactions of Ma-mPEG/starch in the St-g-(Ma-mPEG) copolymers were studied by DSC and TGA. The Tg values showed a higher plasticizer effect in the copolymers obtained from StC. Films were formed from StC-g-(Ma-mPEG) and StB-g-(Ma-mPEG) copolymers, thermal and morphological properties were studied. An increase in the mass ratios of Ma-mPEG and the absence of the glycerol in the formulations formed homogeneous films. StC-g-(Ma-mPEG) 1:3 with 2% concentration showed a potential use as coating in strawberries, presenting a lower weight loss (15.5 ± 5.7%) than the control sample (18.6 ± 3.3%).

Polyelectrolyte Nanoparticles of Amphiphilic Chitosan/Pectin from Banana Peel as Potential Carrier System of Hydrophobic Molecules.

In this study, pectins were extracted from banana wastes Musa paradisiaca under different acidic conditions, obtaining pectins with different degrees of esterification (DE) depending on the acid type and pH. The formation of the polyelectrolyte nanoparticles was evaluated according to the DE of the pectin, the mass ratio of the polymers of pectin to amphiphilic chitosan (AmCh), and their concentration. The properties of the polyelectrolyte nanoparticles were evaluated at different pH and temperatures. The pectin with 24.3% DE formed polyelectrolyte nanoparticles through the electrostatic interaction with AmCh, which was evidenced by changes in the zeta potential and particle size. The study of mass ratio AmCh:Pectin, to get a stable system, showed that it must be at least equal (1:1), or AmCh must be in higher proportion (6:1, 50:1, 100:1), and the polymers concentration must be 1 mg/mL. The study of the temperature effect showed that, when the temperature increases, the particle size decreases, and the pH study showed a stable particle size for the polyelectrolyte nanoparticles in the range of pH 5-6. Nile Red (NR), a hydrophobic molecule, was encapsulated in the polyelectrolyte nanoparticles with a loading capacity of 1.8% and an encapsulation efficiency of 80%.