The effect of chitosan on the bioaccessibility and intestinal permeability of acyclovir.
Eur J Pharm Biopharm
; 136: 147-155, 2019 Mar.
Article
in En
| MEDLINE
| ID: mdl-30682491
ABSTRACT
Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir's bioaccessibility was studied using the dynamic TNO gastro-Intestinal Model (TIM-1). Four epithelial models were used for permeability experiments a Caco-2 cell model in absence and presence of mucus and both rat and porcine excised intestinal segments. Study concentrations of acyclovir (0.8â¯g/l) and chitosan (1.6â¯g/l and 4â¯g/l) were in line with those used in the aforementioned human study. No effect of chitosan was measured on the bioaccessibility of acyclovir in the TIM-1 system. The results obtained with the Caco-2 models were not in line with the in vivo data. The tissue segment models (rat and porcine intestine) showed a negative trend of acyclovir's permeation in presence of chitosan. The Ussing type chamber showed to be the most biopredictive, as it did point to an overall statistically significantly reduced absorption of acyclovir. This model thus seems most appropriate for pharmaceutical development purposes, in particular when interactions between excipients and drugs are to become addressed.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acyclovir
/
Chitosan
/
Intestinal Absorption
/
Jejunum
Limits:
Animals
/
Humans
Language:
En
Journal:
Eur J Pharm Biopharm
Journal subject:
FARMACIA
/
FARMACOLOGIA
Year:
2019
Document type:
Article
Affiliation country:
Netherlands
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS