Transepithelial transport of morphine and mannitol in Caco-2 cells:
the influence of chitosans of different molecular weights and degrees
of acetylation
J. Pharm. Pharmacol., 58 (7):
909 -- 915 (July 2006)Abstract
The object of this study was to compare the effect of chitosans of
different number-average molecular weights (MWs) and degrees of acetylation
(F-A) on transepithelial transport of morphine in Caco-2 cells. Caco-2
monolayers on polycarbonate (PC) membranes (0.5 cm(2)) were incubated
with morphine (10 mu m) or mannitol (55 mu m) for 180 min. Samples
for analysis of morphine (LCMSMS) and mannitol (liquid scintillation)
were drawn at 45, 90, 120 and 180 min. Transepithelial electrical
resistance (TEER) and transmission electron microscopy were used
to monitor cell integrity. in controls, morphine transport was half
that of mannitol. Chitosans affected the transport of morphine and
mannitol similarly. For chitosans with similar F-A (0.32-0.43) and
varying MWs (7-200 kD), transport was increased at MWs of 29 kD or
more. Among chitosans of similar MWs (180-300 kD) and varying F-A
(0.01-0.61), those with the highest F-A (0.61) had the least effect,
while chitosans with F-A/MW 0.01/250 and 0.17/300 promoted the greatest
transport. An F-A/MW of 0.32/200 and 0.43/170 induced a high and
stable transport rate. Chitosans may enhance transepithelial transport
of morphine by the same mechanism as for mannitol. Chitosans with
F-A of 0.3-0.4 and MW of approx. 200 kD seem favourable in this respect.