Evaluation of superporous hydrogel (SPH) and SPH composite in porcine intestine ex-vivo: assessment of drug transport, morphology effect, and mechanical fixation to intestinal wall.
The objective of this study was to investigate the potential of superporous hydrogel (SPH) and SPH composite (SPHC) polymers to enhance the transport of N-alpha-benzoyl-L-arginine ethylester (BAEE) and fluorescein isothiocyanate-dextran 4400 (FD4) across porcine intestinal epithelium ex-vivo, and to study any possible morphological damage to the epithelium by applying these polymers. In addition, the ability of these polymers to attach to the gut wall by mechanical pressure was examined by using a specifically designed centrifuge model. The transport of BAEE and FD4 across the intestinal mucosa was enhanced 2- to 3-fold by applying SPHC polymer in comparison to negative control. No significant morphological damage was observed by applying these polymers inside the intestinal lumen. Moreover, the SPH and SPHC polymers were able to attach mechanically to the intestinal wall by swelling and did not move in the intestinal lumen even when a horizontal force of 13 gms(-2) was applied. In conclusion, these polymers are appropriate vehicles for enhancing the intestinal absorption of peptide and protein drugs.
Dorkoosh
Farid A
FA
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Borchard
Gerrit
G
Rafiee-Tehrani
Morteza
M
Verhoef
J Coos
JC
Junginger
Hans E
HE
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001696:Biomechanical Phenomena; D002498:Centrifugation; D004337:Drug Carriers / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000378:metabolism*; D007583:Jejunum / Q000033:anatomy & histology / Q000378:metabolism*; D016062:Porosity; D013552:Swine
D004337:Drug Carriers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate