Hybrid lipid-biopolymer nanocarrier as a strategy for GBM photodynamic therapy (PDT).

Glioblastoma (GBM) is the most common brain cancer characterized by aggressive and infiltrated tumors. For this, hybrid biopolymer-lipid nanoparticles coated with biopolymers such as chitosan and lipidic nanocarriers (LN) loaded with a photosensitizer (AlClPc) can be used for GBM photodynamic therapy. The chitosan-coated LN exhibited stable physicochemical characteristics and presented as an excellent lipid nanocarrier with highly efficiently encapsulated photosensitizer chloro-aluminum phthalocyanine (AlClPc). LN(AlClPc)Ct0.1% in the presence of light produced more reactive oxygen species and reduced brain tumor cell viability and proliferation. Confirm the effects of in vivo LN applications with photodynamic therapy confirmed that the total brain tumor area decreased without systemic toxicity in mice. These results suggest a promising strategy for future clinical applications to improve brain cancer treatment.

New series of metal complexes by amphiphilic biopolymeric Schiff bases from modified chitosans: Preparation, characterization and effect of molecular weight on its biological applications.

To improve biological activity of chitosans, new Zn(II), Pd(II) and Pt(II) complexes with biopolymeric amphiphilic Schiff bases anchored in different molecular weight chitosans matrices modified with salicylaldehyde and glycidol were prepared. Salicylaldehyde was introduced to generate complexing Schiff base sites in the chitosans matrix while glycidol is intended to increase the water solubility of the resulting biopolymeric complexes. These novel complexes were characterized using various techniques and assayed for antimicrobial and antitumor activity. The effectiveness of modification was evaluated using FTIR spectroscopy, and thermal behavior of the complexes by TG/DTG-DTA. XPRD showed that the crystallinity of the ligand diminished after the metal complexation. Surface morphologies, investigated by SEM, revealed that the complexes are rougher than chitosan matrix, and the presence of metallic ions was confirmed by EDX. Electronic spectra suggested square planar geometry for Pd(II) and Pt(II) complexes. Concerning antimicrobial activity, the novel complexes exhibited higher antibacterial efficiency against Pseudomonas syringae than against the Fusarium graminearum fungi regarding the free ligand. Complexes also exhibited high antitumor effects against the MCF-7 breast cancer cells, with certain selectivity regarding non-tumor cells (Balb/C 3T3 clone A31) depending on concentration and molar mass, indicating that they could potentially be used for antitumor applications.

The influence of reaction parameters on complexation of Zn(II) complexes with biopolymeric Schiff bases prepared from chitosan and salicylaldehyde.

Influence of some reactional parameters as mol ratio (Schiff base:metal), solvent, temperature and reaction time were evaluated in order to improve the extension of complexation during the preparation of zinc complexes of biopolymeric Schiff base from chitosan and salicylaldehyde. Zinc(II) complex was used as a model system in order to improve the degree of complexation for further synthesis of different Schiff bases complexes from other aldehydes and metallic centers. The complexation yields for each synthesis were estimated on the basis of the zinc oxide formed after thermal degradation. Thus thermogravimetry was used to determine the experimental percentage of metal that interact with the free biopolymeric Schiff base. In conclusion, complexation reaction of zinc(II) with biopolymeric Schiff bases was more effective at 40 °C in ethanol as a solvent with intermediary dielectric constant, which resulted in higher metallic contents. Other experimental conditions that resulted in highest degree of complexation were mol ratio 1.0:1.0 (mol/mol, Schiff base:metal), reaction temperature 40 °C and reaction time of 8 h in ethanol. Biological activity of free ligand and its Zn(II) complex obtained under optimized conditions were evaluated against tumor cells.

Synthesis, Characterization and Biological Activities of Biopolymeric Schiff Bases Prepared with Chitosan and Salicylaldehydes and Their Pd(II) and Pt(II) Complexes.

In an attempt to enhance chitosan biological activities, biopolymeric Schiff bases of chitosan and different salicylaldehydes and their palladium(II) and platinum(II) complexes were synthesized and tested. The chemical structures of these derivatives were characterized using ¹H-NMR, FTIR spectroscopy and XPRD. Thermal analysis was done through TGA/DTG-DTA. Electronic absorption spectra and surface morphologies were analyzed by SEM-EDAX. Chitosan and its derivatives were evaluated for their in vitro antimicrobial activity against two common bacterial and fungal plant pathogens Pseudomonas syringae pv. tomato and Fusarium graminearum, respectively, and for their antitumor activity against a human breast cancer cell line (MCF-7). It was found that, compared to the nonmodified chitosan, chitosan modified with Schiff bases and their complexes was highly toxic against the MCF-7 cell line and had antibacterial effects against P. syringea. However, the modified chitosan derivatives had less pronounced antifungal effects against F. graminearum compared to the nonmodified chitosan, suggesting different modes of action.

Synthesis, characterization and biological activity of Cu(II), Ni(II) and Zn(II) complexes of biopolymeric Schiff bases of salicylaldehydes and chitosan.

Schiff bases have been prepared from biopolymer chitosan and salicylaldehyde, 5-methoxysalicylaldehyde, and 5-nitrosalicylaldehyde. Ligands were synthesized in a 1:1.5mol ratio, and their Cu(II), Ni(II) and Zn(II) complexes in a 1:1mol ratio (ligand:metal). Ligands were characterized by 1H NMR and FTIR, resulting in degrees of substitution from 43.7 to 78.7%. Complexes were characterized using FTIR, electronic spectra, XPRD. The compounds were confirmed by the presence of an imine bond stretching in the 1630-1640cm-1 and νMetal-N and νMetal-O at <600cm-1. Electronic spectra revealed that both Cu(II) and Ni(II) complexes present a square plane geometry. The crystallinity values were investigated by X-ray powder diffraction. Thermal behavior of all compounds was evaluated by TGA/DTG and DTA curves with mass losses related to dehydration and decomposition, with characteristic events for ligand and complexes. Schiff base complexes presented lower thermal stability and crystallinity than the starting chitosan. Residues were the metallic oxides as confirmed by XPRD, whose amounts were used in the calculation of the percentage of complexed metal ions. Surface morphologies were analyzed with SEM-EDAX. Preliminary cytotoxicity tests were performed using MTT assay with HeLa cells. Despite the differences in solubility, the free bases presented relatively low toxicity.

Polymeric systems as nanodevices for siRNA delivery.

The delivery of small interfering RNAs (siRNAs) is a promising approach to silencing gene expression aimed at treating infections, cancer, neurodegenerative diseases and various other disorders. Recent progress in this area has been achieved with nanodevices possessing multiple properties and assembled with new, biodegradable, synthetic polymers and polysaccharides. Different synthetic routes and multiple strategies, such as multilayer systems and stimuliresponsive polymers, have been developed to attain high efficiencies. This review covers the most important, promising and successful approaches to improve siRNA delivery. It is a concise report on multiple strategies employed, including cell-specific delivery coupling ligands or antibodies with nanodevices to improve siRNA efficiency and specificity.

Synthesis and evaluation of diethylethylamine-chitosan for gene delivery: composition effects on the in vitro transfection efficiency.

Chitosan has been indicated as a safe and promising polycation vector for gene delivery. However its low transfection efficiency has been a challenging obstacle for its application. To address this limitation, we synthesized chitosan derivatives which had increasing amounts of diethylethylamine groups (DEAE) attached to the chitosan main chain. The plasmid DNA VR1412 (pDNA), encoding the ß-galactosidase (ß-gal) reporter gene was used to prepare nanoparticles with the chitosan derivatives, and the transfection studies were performed with HeLa cells. By means of dynamic light scattering and zeta potential measurements, it was shown that diethylethylamine-chitosan derivatives (DEAE(x)-CH) were able to condense DNA into small particles having a surface charge depending on the polymer/DNA ratio (N/P ratio). Nanoparticles prepared with derivatives containing 15 and 25% of DEAE groups (DEAE(15)-CH and DEAE(25)-CH) exhibited transfection efficiencies ten times higher than that observed with deacetylated chitosan (CH). For derivatives with higher degrees of substitution (DS), transfection efficiency decreased. The most effective carriers showed low cytotoxicity and good transfection activities at low charge ratios (N/P). Vectors with low DS were easily degraded in the presence of lysozyme at physiological conditions in vitro and the nontoxicity displayed by these vectors opens up new opportunities in the design of DEAE-chitosan-based nanoparticles for gene delivery.