Biologically erodable microspheres as potential oral drug delivery systems.
Biologically adhesive delivery systems offer important advantages over conventional drug delivery systems. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.
Mathiowitz
E
E
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA. Edith_Mathiowitz@Brown.edu
Jacob
J S
JS
Jong
Y S
YS
Carino
G P
GP
Chickering
D E
DE
Chaturvedi
P
P
Santos
C A
CA
Vijayaraghavan
K
K
Montgomery
S
S
Bassett
M
M
Morrell
C
C
D000268:Adhesiveness; D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D003652:Decanoic Acids / Q000493:pharmacokinetics; D003998:Dicarboxylic Acids; D001728:Dicumarol / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005650:Fumarates / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D007328:Insulin / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000378:metabolism; D008854:Microscopy, Electron; D008863:Microspheres; D009092:Mucous Membrane / Q000378:metabolism; D010581:Peyer's Patches / Q000378:metabolism; D010957:Plasmids; D011108:Polymers; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000235:genetics / Q000493:pharmacokinetics
D001786:Blood Glucose; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D005650:Fumarates; D007328:Insulin; D011108:Polymers; D001728:Dicumarol; C032005:fumaric acid; C011107:sebacic acid; D001616:beta-Galactosidase