Microfabricated porous silicon particles enhance paracellular delivery of insulin across intestinal Caco-2 cell monolayers.
OBJECTIVE
Novel porous silicon microparticles were fabricated and loaded with fluorescein isothiocyanate (FITC)-insulin, a model hydrophilic pharmacologically active protein, along with varied doses of sodium laurate (C12), a well-known permeation enhancer.


METHODS
Particle and liquid formulations were compared as a function of apical to basolateral flux of FITC-insulin across differentiated human intestinal Caco-2 cell monolayers grown on Transwell inserts.


RESULTS
The flux of FITC-insulin from silicon particles across cell monolayers was nearly 10-fold higher compared with liquid formulations with permeation enhancer and approximately 50-fold compared with liquid formulations without enhancer. By increasing C12 dose per particle with a concomitant decrease in total particles added per monolayer, the percent of FITC-insulin transport resulted in a linear increase up to 25% monolayer coverage.


CONCLUSIONS
Although maintaining monolayer integrity and transepithelial electrical resistance, maximum drug transport (20%/h) was achieved with 0.337 microg C12 dose per particle, and total particle loading at 25% monolayer coverage.
Foraker
Amy B
AB
The Ohio State University, College of Pharmacy, Division of Pharmaceutics, 500 West 12th Avenue, Columbus, Ohio 43210, USA.
Walczak
Rob J
RJ
Cohen
Michael H
MH
Boiarski
Tony A
TA
Grove
Carl F
CF
Swaan
Peter W
PW
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016062:Porosity; D051381:Rats; D012825:Silicon / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
D007328:Insulin; D012825:Silicon