Preparation and ex vivo evaluation of TEC as an absorption enhancer for poorly absorbable compounds in colon specific drug delivery.
In previous studies, it was established that chitosan and its quaternized derivatives are potent enhancers of hydrophilic compounds absorption across intestinal epithelia. The aim of this study was to evaluate the application of a new quaternized chitosan, triethyl chitosan (TEC), in pharmaceutical approaches. TEC was synthesized by a one step process via a 2(2) factorial design to optimize the preparation conditions. In ex vivo experiments, everted rat colon sac was used to determine the effect of TEC on the penetration of hydrophilic compounds of different molecular masses (e.g., sodium fluorescein and brilliant blue) through colonic epithelia in comparison with chitosan at pH 7.4. These studies indicated a significant increase in absorption of sodium fluorescein and brilliant blue in the presence of TEC compared to chitosan. TEC bearing positive charge is able to interact with the tight junctions of colon epithelia and hence increase the permeation of sodium fluorescein and brilliant blue through the tight junctions. This investigation has shown that triethyl chitosan could be used as a penetration enhancer for poorly absorbable compounds in the colon drug delivery system.
Younessi
Parisa
P
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Avadi
Mohammad Reza
MR
Shamimi
Kooroush
K
Sadeghi
Assal Mir Mohammad
AM
Moezi
Leila
L
Nahid
Elaheh
E
Bayati
Khosrow
K
Dehpour
Ahmad Reza
AR
Rafiee-Tehrani
Morteza
M
D000277:Adjuvants, Pharmaceutic / Q000138:chemical synthesis / Q000737:chemistry*; D000704:Analysis of Variance; D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D016503:Drug Delivery Systems; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008970:Molecular Weight; D051381:Rats; D018709:Statistics, Nonparametric
D000277:Adjuvants, Pharmaceutic; D001557:Benzenesulfonates; C502513:triethyl chitosan; D048271:Chitosan; C006796:brilliant blue; D019793:Fluorescein