PEGylation and folate conjugation effects on the stability of chitosan-tripolyphosphate nanoparticles.

Chitosan-based nanoparticles (Ch-NPs) prepared via ionotropic gelation of Ch with sodium tripolyphosphate (TPP) have been widely examined as potential drug carriers. Yet, recent studies have shown these particles to be unstable in model (pH 7.2-7.4) physiological media. To this end, here we explored the possibility of improving TPP-crosslinked Ch-NP stability through chemical Ch modification. Specifically, Ch samples with either 76% or 92% degrees of deacetylation (DD) were grafted with either polyethylene glycol (PEG), a hydrophilic molecule, or folic acid (F), a hydrophobic molecule. Limited variation in dispersion light scattering intensity, particle size and apparent ζ-potential, and lack of macroscopic precipitation were chosen as analytical evidence of dispersion stability. TPP titrations were performed to determine the optimal TPP:glucosamine molar ratio for preparing particles with near 200-nm diameters, which are desirable for systemic administration of drugs, cellular uptake, and enhancing NP blood circulation. Both DD and Ch modification influenced the particle formation process and the evolution in NP size and ζ-potential upon 30-day storage in virtually salt-free water at 25 °C and 37 °C, where the NPs underwent partial aggregation (along with possible dissolution and swelling) but remained colloidally dispersed. Under model physiological (pH 7.2; 163 mM ionic strength) conditions, however (where the chitosan amine groups were largely deprotonated), the particles quickly became destabilized, evidently due to particle dissolution followed by Ch precipitation. Overall, within the degrees of substitution used for this work (~1% for PEG, and 3 and 6% for F), neither PEG nor F qualitatively improved Ch-NP stability at physiological pH 7.2 conditions. Thus, application of TPP-crosslinked Ch-NPs in drug delivery (even when Ch is derivatized with PEG or F) should likely be limited to administration routes with acidic pH (at which these NPs remain stable).

Chitosan-PEG-folate-Fe(III) complexes as nanocarriers of epigallocatechin-3-gallate.

Controlled release nanocarriers systems are promising for the administration of epigallocatechin-3-gallate (EGCG) in the treatment and prevention of several diseases. Therefore, the stability and therapeutic effects of EGCG must be enhanced from an encapsulation strategy. Thus, this research aims to explore a method to prepare EGCG nanocarriers based on coordination complexes from Fe (III) ions and blends of modified chitosan (Ch) with polyethylene glycol (PEG) and folic acid (F). Different degrees of deacetylated Ch and conjugated with F were evaluated, whose values determined the final amount of Fe (III) in the complexes. All these complexes were amorphous with a polydispersity index (PDI) higher than 0.3. The assembling and homogeneity were improved adding tripolyphosphate (TPP), yielding particle sizes near 200 nm, and PDI values of 0.2, measured by DLS and TEM. The EGCG encapsulation efficiency was about 60%, and the loading capacity was in the range of 26% to 50%. The EGCG release profile displayed a controlled release without a burst effect, providing the best fit with the Korsmeyer-Peppas model, indicating interactions among EGCG and the polymer matrix. The above results reveal the potential of these nanocarriers as suitable systems for controlled release and have not yet been reported.

Interplay between structure and dynamics in chitosan films investigated with solid-state NMR, dynamic mechanical analysis, and X-ray diffraction.

Modern solid-state NMR techniques, combined with X-ray diffraction, revealed the molecular origin of the difference in mechanical properties of self-associated chitosan films. Films cast from acidic aqueous solutions were compared before and after neutralization, and the role of the counterion (acetate vs Cl(-)) was investigated. There is a competition between local structure and long-range order. Hydrogen bonding gives good mechanical strength to neutralized films, which lack long-range organization. The long-range structure is better defined in films cast from acidic solutions in which strong electrostatic interactions cause rotational distortion around the chitosan chains. Plasticization by acetate counterions enhances long-range molecular organization and film flexibility. In contrast, Cl(-) counterions act as a defect and impair the long-range organization by immobilizing hydration water. Molecular motion and proton exchange are restricted, resulting in brittle films despite the high moisture content.