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Agu, Remigius U.; Dang, Hoang Vu; Jorissen, Mark; Willems, Tom; Vandoninck, Sandy; Lint, Johan Van; Vandenheede, Jackie V.; Kinget, Renaat; Verbeke, Norbert

doi:10.1023/a:1025028410131

Cited by 15 publications

(4 citation statements)

References 25 publications

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“…Agu et al also suggest that LAT-1 and LAT-2 are not expressed in the human nasal epithelium and additional amino acid transporters also appear to have limited expression. 10 During their investigations, relatively high K m values for phenylalanine uptake were determined, which also may be suggestive of the limited expression of amino acid transporters in these nasal epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Transport of tyrosine and phenylalanine across rat nasal mucosa was suggested to be via an active, saturable, stereo-specific and energy-dependent uptake process, and competitive inhibition between these two amino acids was also observed. 11 L-phenylalanine transport across a human nasal primary cell culture system was also studied, 10 and the influence of temperature, concentration and presence of other amino acids on L-phenylalanine transport were investigated. The amino acid was shown to cross the human nasal epithelium by a polarized, saturable ( K m = 1.23 mM; V max = 805.1 nmol/mg protein/min) and sodium dependent process.…”

Section: Introductionmentioning

confidence: 99%

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Permeation and Systemic Absorption of R- and S-Baclofen Across the Nasal Mucosa

Zhang

Schmidt

Murry

et al. 2011

Journal of Pharmaceutical Sciences

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Baclofen, an antispasmodic agent that acts as a GABAB agonist, resembles phenylalanine in structure and has been reported to be a substrate of the large amino acid transporter, LAT-1. The objective of this study was to investigate the absorption of baclofen across the nasal mucosa both in vitro and in vivo. Baclofen transport was measured across excised bovine olfactory and respiratory mucosae to investigate site-specific uptake of baclofen, and the intranasal bioavailability of R- and S- baclofen was determined in rats. Increasing flux with increasing baclofen donor concentration and the absence of polarized transport was observed in vitro and similar distribution profiles were observed for both enantiomers following intranasal administration in rats. The absence of stereospecificity in nasal absorption indicates limited involvement of the amino acid or other transporters in the nasal absorption of baclofen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Permeation and Systemic Absorption of R- and S-Baclofen Across the Nasal Mucosa

Zhang

Schmidt

Murry

et al. 2011

Journal of Pharmaceutical Sciences

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“…For characterizing the transport pathway of insulin, three additives, i.e., L-leucine, chochicine, and poly-L-lysine, were coadministered with insulin, respectively. L-Leucine 44) was reported to be actively transported across mucosa by consuming energy of ATP. Our results indicate that there is no competition phenomenon when insulin was coadministered with L-leucine, suggesting that insulin across HOIEC monolayer may not be through the active transport.…”

Section: Discussionmentioning

confidence: 99%

Sublingual Delivery of Insulin: Effects of Enhancers on the Mucosal Lipid Fluidity and Protein Conformation, Transport, and in Vivo Hypoglycemic Activity

Cui

Lü

Xiao

et al. 2005

Biological & Pharmaceutical Bulletin

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The purposes of this study were to evaluate effects of enhancers for sublingual delivering insulin on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity in normal rats. The effects on sublingual mucosa, and aggregation states of insulin were estimated using fluorescence polarization, and circular dichroism method, respectively. The human immortalized oral epithelial cell monolayer was used for evaluating transport of insulin. Hydroxylpropyl-b b-cyclodextrin (HP-b b-CD), chitosan, polyethylene-polypropylene glycol, polyoxyethylene lauryl ether, polysorbate 80, egg lecithin, or oleic acid, was used as a penetration enhancer, respectively. The fluidity of sublingual mucosal lipid was markedly reduced by these enhancers excluding polysorbate 80, and the secondary structure of the mucosal proteins was also influenced by these enhancers. The hexamers of insulin were dissociated to monomers only by chitosan, polyoxyethylene lauryl ether, and egg lecithin. Nonetheless, plasma glucose levels in normal rats were significantly lowered after sublingual administration of insulin with an enhancer compared with those without an enhancer at the same time-point. The enhancing effects may be due to one or multiple factors: increasing the mucosal lipid fluidity, directly loosing the tight junction of epithelia, and dissociating the hexamers of insulin to monomers. Among these, the opened tight junction may correlate most with the enhancing effect in the mucosal permeability. Because the aggregates of insulin exist, the dissociation of the aggregates by an enhancer would benefit the permeability.

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“…Towards the in vitro testing of nasal formulations, cultured nasal epithelium is regarded as a useful model for the study of nasal drug absorption, in that it allows a preliminary assessment of the permeability, toxicity, metabolism and transport of potential therapeutic agents. 29 A useful surrogate for human nasal epithelia is provided by Calu-3 cells. 30,31 These are a well-characterised human respiratory tract epithelial cells that can be cultured as confluent monolayers at the airmedium interface.…”

Section: Introductionmentioning

confidence: 99%

A once-a-day dosage form for the delivery of insulin through the nasal route: in vitro assessment and in vivo evaluation

et al. 2013

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An in situ thermogelling, mucoadhesive formulation based on N-trimethyl chitosan chloride has been evaluated for its potential to affect the transmucosal delivery of insulin via the nasal route. In vitro studies at a physiologically relevant temperature (ca. 35 °C) have shown that the formulation releases most of its insulin load (ca. 70%) in a non-Fickian manner during the timescale over which the sol-to-gel transition (ca. 8 min) takes place, and also that, once gelation is complete, the release of the remainder of the therapeutic content follows first order kinetics over at least sixty minutes. Investigations on the effects of the application of the same formulation to a modelled nasal mucosa (Calu-3 cell monolayer) have indicated the capability of the formulation to induce the transient opening of tight junctions. Cytotoxic investigations have shown that the formulation exhibits negligible detrimental effects to the integrity of these monolayers. The in vivo potential of the nasal formulation to act as a once-a-day dosage form for the intranasal delivery of insulin has been demonstrated in a diabetic-rat model

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Abstract: Based on the results of this study, one may postulate that the human nasal epithelium expresses L-amino acid transporters. More studies are necessary for detailed characterization of the transporters.

Cited by 15 publications

References 25 publications

Permeation and Systemic Absorption of R- and S-Baclofen Across the Nasal Mucosa

Permeation and Systemic Absorption of R- and S-Baclofen Across the Nasal Mucosa

Sublingual Delivery of Insulin: Effects of Enhancers on the Mucosal Lipid Fluidity and Protein Conformation, Transport, and in Vivo Hypoglycemic Activity

A once-a-day dosage form for the delivery of insulin through the nasal route: in vitro assessment and in vivo evaluation

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