In vitro cell models to study nasal mucosal permeability and metabolism

Schmidt, M; Peter, Hagen; Lang, Steffen; Ditzinger, Günter; Merkle, Hans P.

doi:10.1016/s0169-409x(97)00061-6

Cited by 111 publications

(85 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanistic aspects of nasal drug delivery are easier performed in-vitro. It is also easier to separate the process of drug permeation across the epithelium from subsequent events such as biodistribution and elimination, as well as local blood flow (Schmidt et al 1998). Other advantages of in-vitro models used in studying nasal drug delivery include : fast assessment of the potential permeability and metabolism of a drug ; rapid screening of toxicity of drugs and excipients ; the opportunity to elucidate the molecular mechanisms of drug transports across the epithelium and pathways of degradation and ways of preventing such degradation ; the possibility of using human tissues ; and a reduction in the number of animals used at later stages of the drug development process.…”

Section: In Vitro\ex Vivo Modelsmentioning

confidence: 99%

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Ugwoke

Verbeke

Kinget

2001

Journal of Pharmacy and Pharmacology

295

158

View full text Add to dashboard Cite

Nasal drug administration has frequently been proposed as the most feasible alternative to parenteral injections. This is due to the high permeability of the nasal epithelium, allowing a higher molecular mass cut-off at approximately 1000 Da, and the rapid drug absorption rate with plasma drug profiles sometimes almost identical to those from intravenous injections.Despite the potential of nasal drug delivery, it has a number of limitations. In this review, the anatomy and physiology of the nasal cavity, as well as ciliary beating and mucociliary clearance as they relate to nasal drug absorption, are introduced. The rationale for nasal drug delivery and its limitations, some factors that influence nasal drug absorption, and the experimental models used in nasal drug delivery research are also reviewed. Nasal mucoadhesion as a promising method of nasal absorption enhancement is discussed, and factors that influence mucoadhesion, as well as safety of nasal mucoadhesive drug delivery systems are reviewed in detail.Nasal drug administration is presently mostly used for local therapies within the nasal cavity.

show abstract

Section: In Vitro\ex Vivo Modelsmentioning

confidence: 99%

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Ugwoke

Verbeke

Kinget

2001

Journal of Pharmacy and Pharmacology

295

158

View full text Add to dashboard Cite

show abstract

“…The nasal route is also favourable for the delivery of peptides such as calcitonin, buserelin, due to the avoidance of the metabolism in the gastrointestinal tract. The most relevant anatomical region in the nasal cavity concerning systemic nasal drug delivery is the respiratory epithelium lining the middle and inferior turbinate (Schmidt et al 1998). For successful formulation of a nasal delivery system, testing on reliably established in vitro cell culture, ex vivo tissue and in vivo animal models are crucial (Chien et al 1992).…”

Section: Introductionmentioning

confidence: 99%

“…The shortage of human nasal tissue and the low reproducibility have prompted to seek an alternative to primary cultures of nasal epithelial cells, that is, the use of nasal epithelial cell lines. Cultured immortalized nasal epithelial cells are widely used models for drug toxicity and metabolism studies, since they are known to express important biological features like intercellular tight and adherens junctions, mucin secretion, cilia, and various transporters, resembling those found in in vivo systems (Schmidt et al 1998). The use of an immortalized cell line has the advantages of ease of culture, lower cost, genetic homogeneity and reproducibility of the results.…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid and hydrocortisone strengthen the barrier function of human RPMI 2650 cells, a model for nasal epithelial permeability

et al. 2012

View full text Add to dashboard Cite

The nasal pathway represents an alternative route for non-invasive systemic administration of drugs. The main advantages of nasal drug delivery are the rapid onset of action, the avoidance of the first-pass metabolism in the liver and the easy applicability. In vitro cell culture systems offer an opportunity to model biological barriers. Our aim was to develop and characterize an in vitro model based on confluent layers of the human RPMI 2650 cell line. Retinoic acid, hydrocortisone and cyclic adenosine monophosphate, which influence cell attachment, growth and differentiation have been investigated on the barrier formation and function of the nasal epithelial cell layers. Real-time cell microelectronic sensing, a novel label-free technique was used for dynamic monitoring of cell growth and barrier properties of RPMI 2650 cells. Treatments enhanced the formation of adherens and tight intercellular junctions visualized by electron microscopy, the presence and localization of junctional proteins ZO-1 and b-catenin demonstrated by fluorescent immunohistochemistry, and the barrier function of nasal epithelial cell layers. The transepithelial resistance of the RPMI 2650 cell model reached 50 to 200 X 9 cm 2 , the permeability coefficient for 4.4 kDa FITC-dextran was 9.3 to 17 9 10 -6 cm/s, in agreement with values measured on nasal mucosa from in vivo and ex vivo experiments. Based on these results human RPMI 2650 cells seem to be a suitable nasal epithelial model to test different pharmaceutical excipients and various novel formulations, such as nanoparticles for toxicity and permeability.

show abstract

“…84,95 This method is used for evaluating the transportation and metabolism of peptides including insulin. [96][97][98] In spite of the advantages of this method, there is a difficulty in obtaining adequate amount of epithelial cells because biopsies yield limited amount of nasal epithelial cells.…”

Section: Fig 3: Various Models For Intra Nasal Drug Transport and Abmentioning

confidence: 99%

Untitled

2017

IJPSR

View full text Add to dashboard Cite

Intra nasal drug delivery system (INDDS) has emerged as a noninvasive alternative for delivering peptides, proteins and other therapeutic agents, specifically to CNS (Central nervous system). This route is well suitable for systemic delivery because of high vasculature, permeability, elimination of hepatic first pass metabolism and low enzymatic environment of the nasal cavity. This route of delivery is especially suited to treat CNS disorders like -neurodegenerative diseases, mood disorders, cognitive dysfunctioning etc., due to drugs ability to directly reach the brain by passing blood brain barrier (BBB). It is also a well suited delivery route for the biotechnological products like DNA plasmids, hormone, proteins, peptides, DNA vaccines to give enhanced bioavailability. A wide variety of therapeutic compounds may be administered intra-nasally for topical, systemic and CNS disorders. In this review, we have focussed on the nasal passage anatomical pathway leading to CNS drug delivery, different factors affecting nasal absorption, bioavailability barriers, vaccines and other therapeutic, biologically active molecules delivered via intra nasal route and strategies to improve nasal absorption. We have also outlined various in vitro and in vivo cellular models for nasal drug absorption and permeability studies.

show abstract

In vitro cell models to study nasal mucosal permeability and metabolism

Cited by 111 publications

References 106 publications

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Retinoic acid and hydrocortisone strengthen the barrier function of human RPMI 2650 cells, a model for nasal epithelial permeability

Untitled

Contact Info

Product

Resources

About