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Intestinal Uptake of Polymer Microspheres in the Rabbit Studied with Confocal Microscopy

Brown University, RI, USA

K. -P. Yip

Brown University, RI, USA

E. Mathiowitz

Brown University, RI, USA, Edith_Mathiowitz{at}Brown.edu

This study characterizes the ability of several polymer formulations to penetrate the absorptive epithelium and lymphoid-associated tissue of the gastrointestinal tract. Using phase inversion nano encapsulation and solvent diffusion, formulations with variable size ranges consisting of either poly(fumaric-co-sebacic)anhydride, poly(lactide-co-glycolide), polystyrene, or polycaprolactone were fabricated and administered to an isolated loop in the small intestine of rabbits. Particles were loaded with a fluorescent dye for detection. Following a period of incubation, animals were sacrificed and the tissue was explanted and processed for histology. Confocal laser scanning microscopy (CLSM) was used to track the microspheres and two separate emission detectors were used to isolate the dye from background. Particles that possess bioadhesiveness in the micron size range could be localized to the absorptive epithelium while larger particles and formulations with low bioadhesiveness failed to penetrate enterocytes and were taken up preferentially in the Peyer’s patches. This work demonstrates that the surface chemistry of oral formulations can ultimately determine the fate and can aid in designing delivery vehicles for a variety of therapeutics currently plagued with poor oral bioavailability.

Key Words: bioadhesion • nanosphere • uptake • bioavailability • polyanhydride • phase inversion microspheres • nanospheres • confocal • oral uptake

Journal of Bioactive and Compatible Polymers, Vol. 19, No. 4, 247-266 (2004)
DOI: 10.1177/0883911504045275


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