Affiliation:
1. Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany
Abstract
Abstract
Objectives
The kinetics of drug absorption for nasally administered drugs are often studied using excised mucosal tissue. To avoid the disadvantages of animal experiments, cellular in-vitro models have been established. This study describes the optimization of culture conditions for a model based on the RPMI 2650 cell line, and an evaluation of this model's value for drug absorption studies.
Methods
The cells were cultured in two serum-free media, serum-reduced variants or minimum essential medium (MEM) containing 5–20% serum. Cell seeding efficiency and proliferation behavior were evaluated in addition to viability and attachment following cryopreservation and thawing. Cells were cultured on different filter inserts for varying cultivation times. The epithelial barrier properties were determined by measuring transepithelial electrical resistance (TEER). Permeability was assessed using marker substances.
Key findings
Serum supplementation of medium was necessary for cultivation, whereas the serum concentration showed little impact on proliferation and attachment following cryopreservation. A pronounced dependence of TEER on medium and filter material was observed. An optimized model cultured with MEM containing 10% serum on polyethylene terephthalate exhibited permeability that was similar to excised nasal mucosa.
Conclusions
These data indicate that this model could be an appropriate alternative to excised mucosa for the in-vitro evaluation of nasal drug absorption.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Reference37 articles.
1. Nasal delivery of high molecular weight drugs;Ozsoy;Molecules,2009
2. Pharmacokinetics, efficacy, and tolerability of fentanyl following intranasal versus intravenous administration in adults undergoing third-molar extraction: a randomized, double-blind, double-dummy, two-way, crossover study;Christrup;Clin Ther,2008
3. Enhancement of the systemic and CNS specific delivery of L-dopa by the nasal administration of its water soluble prodrugs;Kaoh;Pharm Res,2000
4. Pharmacokinetics and pharmacodynamics of nasally delivered midazolam;Haschke;Br J Clin Pharmacol,2010
5. New strategies to improve the intranasal absorption of insulin;Duan;Drug Discov Today,2010
Cited by
50 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献