Preparation and characterization of lectin-latex conjugates for specific bioadhesion.

This paper reports on the preparation and characterization of certain bioadhesive model drug deliver systems formed by a carrier (e.g. modified nanoparticles of polystyrene) and a ligand (e.g. tomato lectin, asparagus pea lectin, Mycoplasma gallisepticum lectin or albumin). Three different manufacturing methods (carbodiimide and glutaraldehyde coupling and physical adsorption) were studied. The activity of the lectin-latex conjugates and albumin-latex conjugate (control) were tested with gastric pig mucin. The manufacturing method had an insignificant effect on the activity, but all lectin-latex conjugates interacted two or three times more with mucin than with the control.

Bioadhesion of lectin-latex conjugates to rat intestinal mucosa.

PURPOSE: The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS: These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), and bovine serum albumin (BSA) as control, to poly(styrene) latexes. RESULTS: Using mucosa samples without Peyer's patches (PP), the extent of interaction of all three lectin-latex conjugates with the mucosa decreased from duodenum to ileum, probably due to progressive diminution of the mucin concentration along the gastrointestinal tract. The following order of interaction of the conjugates with the mucus gel layer was observed: TL > ML = AL (p < 0.05). For each lectin, these results corresponded well to the concentration of its specific sugar in the mucus. Using intestinal samples with PP, an important increase of interaction of the conjugates with the mucosa was found for ML (about 25%) and AL (about 50%), whereas the interaction of TL decreased about 25%. CONCLUSIONS: Photomicrographs with fluorescent latexes have confirmed the specificity of the ML- and AL-latex conjugates for the PP region and of the TL-latex conjugates for the mucus gel.

Mucoadhesion of latexes. I. Analytical methods and kinetic studies.

A Fourier transform infrared spectroscopy/attenuated total reflection technique for direct quantification of adsorbed poly(styrene) latexes on rat intestinal mucosa was developed for deposited latex amounts up to 1.5 g/m2. The method agreed well with another dosage assay of adsorbed particles by turbidimetry after denaturation of the mucus. Adsorption kinetics were made under static conditions at latex concentrations of 4 g/L in physiological saline. Ninety percent of equilibrium was reached after 10 min for a particle size of 230 nm, 20 min for a size of 320 nm, and 30 min for a size of 670 nm. The plateaus were between 0.6 and 0.9 g/m2 (adsorbed mass per apparent surface of mucosa). The first phase of the kinetics was theoretically approached by a diffusion model in the suspension medium. Mucosa from rat jejunum and ileum could be considered as a homogeneous biological model for latex adsorption.

Mucoadhesion of latexes. II. Adsorption isotherms and desorption studies.

Adsorption isotherms of poly(styrene) latexes on rat intestinal mucosa were studied under static conditions and analyzed according to different isotherm classifications. Isotherms of latexes with a particle size up to 670 nm had the characteristic shape of a disperse adsorbate on a porous adsorbent. Plateaus were reached at latex concentrations of about 2.5 g/L. The results indicated an increase in adsorption with the size and the hydrophilicity of the latexes. Typically, a surfactant-free carboxylate latex of 230 nm had a plateau of 0.66 g/m2, and a latex of 320 nm with added sodium dodecyl sulfate had a plateau of 0.881 g/m2. Surfactant-free carboxylate latex of 2 microns had a Langmuirian isotherm with a plateau level of 2.616 g/m2, which corresponded to a monolayer of adsorbed particles on the surface of mucosa. Desorption studies showed that the adsorption was irreversible. Adhesion to the mucous gel layer would therefore be limited by the mucus turnover.