pectins and 6-carboxyfluorescein

The permeation modulating effects of 5 natural polymers; low-ester, amidated and high-ester pectin, as well as hyaluronic acid and chitosan were tested at two different molecular weights each. The model membrane was methotrexate treated HT29 cells grown for 2 or 3 weeks, respectively, thereby differing in the amount of goblet cells and hence mucus. The pectins decreased the permeation of the paracellular marker carboxyfluorescein. Free acid groups and a high molecular weight increased this membrane protective effect. Chitosan displayed pronounced and hyaluronic acid modest permeation enhancing properties. In this case, a low molecular weight accentuated the effect. In all cases, the permeation modulating properties were reduced by mucus.

Topics: Chitosan; Excipients; Fluoresceins; Fluorescent Dyes; Goblet Cells; HT29 Cells; Humans; Hyaluronic Acid; Methotrexate; Molecular Weight; Mucus; Pectins; Permeability; Polymers

Insulin-loaded calcium pectinate nanoparticles were prepared as a potential colonic delivery system by ionotropic gelation with calcium ions. The effects of pectin molecular weight (Mv) and formulation pH on the characteristics of the nanoparticles were evaluated. Commercial pectins, LM101 and LM104, with respective degrees of esterification of 36% and 28%, were depolymerized by mechanical milling to give Mv ranging from 89 to 5.6 kDa. Milled pectins did not yield nanoparticles with significantly different mean diameter and insulin association efficiency (AE) compared to nanoparticles of unmilled pectins. LM104 nanoparticles had smaller variation in mean size than the LM101 nanoparticles. Formulation pH significantly influenced the AE and stability of the nanoparticles. Increasing the pH from 2 to 3 enhanced the AE by three-fold, from 32.76% to 93.31%, at an insulin loading concentration of 80 U/mL. This increase in AE was correlated to the charge density on the pectin molecules as a function of pH. Subsequent release of associated insulin from the nanoparticles was dependent on the extent of dilution of the nanoparticle dispersion and the pH of the dissolution medium. Cross-flow filtration could be used to separate the nanoparticles from unassociated ions and molecules, without compromising the characteristics of the nanoparticles.

Topics: Calcium; Fluoresceins; Hydrogen-Ion Concentration; Insulin; Microspheres; Molecular Weight; Nanotechnology; Pectins; Technology, Pharmaceutical