ABSTRACT
The fate of macromolecules of biological or pharmacological interest that enter the mucus barrier is a current field of investigation. Studies of the interaction between the main constituent of mucus, mucins, and molecules involved in topical transmucoidal drug or gene delivery is a prerequisite for nanomedicine design. We studied the interaction of mucin with the bio-inspired arginine-derived amphoteric polymer d,l-ARGO7 by applying complementary techniques. Small angle X-ray scattering in bulk unveiled the formation of hundreds of nanometer-sized clusters, phase separated from the mucin mesh. Quartz microbalance with dissipation and neutron reflectometry measurements on thin mucin layers deposited on silica supports highlighted the occurrence of polymer interaction with mucin on the molecular scale. Rinsing procedures on both experimental set ups showed that interaction induces alteration of the deposited hydrogel. We succeeded in building up a new significant model for epithelial tissues covered by mucus, obtaining the deposition of a mucin layer 20 Å thick on the top of a glycolipid enriched phospholipid single membrane, suitable to be investigated by neutron reflectometry. The model is applicable to unveil the cross structural details of mucus-covered epithelia in interaction with macromolecules within the Å discreteness.
Subject(s)
Models, Biological , Mucins/chemistry , Mucins/metabolism , Mucus/chemistry , Mucus/metabolism , Algorithms , Animals , Biopolymers/chemistry , Humans , Molecular Structure , Mucous Membrane/innervation , Mucous Membrane/metabolism , Nanoparticles/chemistry , Organ Specificity , Spectrum AnalysisABSTRACT
Metal cations (Mn(2+) or Ca(2+)) in aqueous dispersions of mixtures of dioleoylphosphatidylethanolamine (DOPE) and poly(ethylene glycol)-functionalized DOPE (DOPE-PEG(350)) induce, above a certain amount of the PEG lipid component, a phase transition from the inverted hexagonal phase H(II) to the bicontinuous inverted cubic phase Q(224) with space group Pn3m. The process is driven by the decrease of free elastic energy due to the Gaussian curvature of the cubic phase. The structural characterization of the phase behavior over the whole explored range of DOPE-PEG/DOPE weight ratio (3-25%) is reported, focusing on the role of the metal cation in the formation of the 3D cubic lattice. This result may represent a significant progress toward a design-based approach to drug delivery.
