Search

Mucoadhesive materials adhere persistently to mucosal surfaces. A mucoadhesive delivery system could therefore facilitate the controlled release of drugs and optimize their bioavailability in mucosal tissues. Polysaccharides are the most versatile class of natural polymers for transmucosal drug delivery. We used microviscosimetry to explore the mucoadhesion of a library of polysaccharide families with diverse structural characteristics as a first step toward the rational design of mucoadhesive polysaccharide-based nanoformulations. Here we show that the magnitude of deviation between the viscosity of mixed polysaccharide-mucin solutions and the corresponding individual stock solutions can indicate underlying molecular interactions. We found that nonlinear monotonic curves predicted a correlation between the magnitude of interaction and the ability of polysaccharide coils to contract in the presence of salt (i.e., chain flexibility). Charge-neutral polysaccharides such as dextran and Streptococcus thermophilus exopolysaccharide did not interact with mucin. Synchrotron small-angle X-ray scattering (SAXS) data supported the previously described structural features of mucin. Furthermore, high-q scattering data (i.e., sensitive to smaller scales) revealed that when mucin is in dilute solution (presumably in an extended conformation) in the presence of low-M w alginate, its structure resembles that observed at higher concentrations in the absence of alginate. This effect was less pronounced in the case of high-M w alginate, but the latter influenced the bulk properties of mucin-alginate mixtures (e.g., hydrodynamic radius and relative viscosity) more prominently than its low-M w counterpart. [ABSTRACT FROM AUTHOR]

Syntheticand natural mucoadhesive biomaterials in optimized galenicalformulations are potentially useful for the transmucosal deliveryof active ingredients to improve their localized and prolonged effects.Chitosans (CS) have potent mucoadhesive characteristics, but the exactmechanisms underpinning such interactions at the molecular level andthe role of the specific structural properties of CS remain elusive.In the present study we used a combination of microviscosimetry, zetapotential analysis, isothermal titration calorimetry (ITC) and fluorescencequenching to confirm that the soluble fraction of porcine stomachmucin interacts with CS in water or 0.1 M NaCl (at c< c*; relative viscosity, ηrel, ∼ 2.0 at pH 4.5 and 37 °C) via a heterotypic stoichiometricprocess significantly influenced by the degree of CS acetylation (DA).We propose that CS–mucin interactions are driven predominantlyby electrostatic binding, supported by other forces (e.g., hydrogenbonds and hydrophobic association) and that the DA influences theoverall conformation of CS and thus the nature of the resulting complexes.Although the conditions used in this model system are simpler thanthe typical in vivo environment, the resulting knowledge will enablethe rational design of CS-based nanostructured materials for specifictransmucosal drug delivery (e.g., for Helicobacterpyloristomach therapy). [ABSTRACT FROM AUTHOR]

Chitosan(CS) is a family of linear polysaccharides with diverseapplications in medicine, agriculture, and industry. Its bioactiveproperties are determined by parameters such as the degree of acetylation(DA), but current techniques to measure the DA are laborious and requirelarge amounts of substrate and sophisticated equipment. It is alsochallenging to monitor the fate of chitosan-based nanoparticles (CS-NPs)in vitro because current tools cannot measure their enzymatic or chemicaldegradation. We have developed a method based on the Försterresonance energy transfer (FRET) that occurs between two independentfluorescent proteins fused to a CS-binding domain, who interact withCS polymers or CS-NPs. We used this approach to calibrate a simpleand rapid analytical method that can determine the DA of CS substrates.We showed unequivocally that FRET occurs on the surface of CS-NPsand that the FRET signal is quenched by enzymatic degradation of theCS substrate. Finally, we provide in vitro proof-of-concept that theseapproaches can be used to label CS-NPs and colocalize them followingtheir interactions with mammalian cells. [ABSTRACT FROM AUTHOR]