Author
Liu, Linshu | |
Fishman, Marshall | |
Hicks, Kevin | |
KENDE, MEIR - USAMRI, FREDERICK, MD |
Submitted to: Biomaterials
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/1/2004 Publication Date: 12/31/2004 Citation: Liu, L.S., Fishman, M.L., Hicks, K.B., Kende, M. Interaction of various pectin formulations with porcine colonic tissues. Biomaterials.26 (2005)p.5907-5916. Interpretive Summary: The need to add value to pectin-rich agricultural residues from fruit juice processing has prompted us to develop pectin as a drug carrier for pharmaceutical applications. The interaction of pectin formulations and mucins (a type of protein), which covers the surfaces of the gastrointestinal (G.I.) tract, is the key step to successful oral drug delivery. This study explored the mechanism, by which pectin bound to mucin to form network structures and release the incorporated drugs. The study also suggested a new strategy to effectively protect the G.I. tract from toxin irritation by the use of pectin derivatives as protective barriers. This research should be of help to fruit growers and processors by increasing the demand for, and value of pectin. Technical Abstract: Pectins of low and high degrees of esterification, as well as pectin derivatives carrying primary amines, were investigated for gel forming ability with mucosal tissues. The combination of scanning electronic microscopy and small deformation dynamic mechanical studies revealed that pectins with higher net electrical charges are more bioadhesive than the less charged ones. Both the negatively charged pectin formulation, P-25, and the positively charged formulation, P-N, were able to synergize with the mucus to produce rheologically strengthened gels. The highly esterified pectin, P-94, also synergized with the mucosal glycoproteins to form a gel structure via coil entanglements. The ex vivo studies further confirmed the microstructures of mucus gel networks with adsorbed pectins. When incubated with porcine intestinal mucus membrane, P-94 gels were found generally bound to the lumen area, P-25 gels were able to penetrate deeply near the wall area, P-N gels interacted with mucins via electrostatic bonding and dispersed into the whole area from the lumen to the wall. Hence, both P-N and P-94, by enhancing the protective barrier properties of mucus systems, may be useful alternatives for the treatment of mucus related irritation and infection. In drug delivery systems, P-N and P-25 would deliver incorporated drugs mainly by pectin dissolution, while a diffusion mechanism would release drugs from P-94 gels. |