Mucociliary clearance and drug delivery via the respiratory tract

Lansley, Alison B.

doi:10.1016/0169-409x(93)90014-u

Cited by 50 publications

(22 citation statements)

References 89 publications

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“…The greater quantity of nasal mucus is secreted from the submucosal glands. These glands are composed of both mucus cells (which secrete the mucus gels) and serous cells that produce a watery fluid (Lansley 1993). There are an estimated 100 000 seromucous glands in the human nose (Tos 1983).…”

Section: Nasal Secretion and Mucus Layermentioning

confidence: 99%

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Ugwoke

Verbeke

Kinget

2001

Journal of Pharmacy and Pharmacology

295

158

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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.

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Section: Nasal Secretion and Mucus Layermentioning

confidence: 99%

The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Ugwoke

Verbeke

Kinget

2001

Journal of Pharmacy and Pharmacology

295

158

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“…In contrast, despite the deposition of nearly half (deposition fraction 0.45) of the exposure aerosols, the nasal absorption contributed only 12.5% to the total absorption (Table 2). This was presumably due to dissolution-controlled, slow absorption of the poorly soluble fluorescein together with rapid mucociliary clearance transporting the solute into the GI tract with its typical rate of 5-20 mm/min and kinetic half-life <10 min (Byron and Phillips 1990;Lansley 1993). Moreover, it was found that 63.3% of the total absorption was derived from the GI regions where the aerosols were not delivered directly, but were transported from the nasal and lung regions by the respective mucociliary clearance systems (Table 2).…”

Section: Discussionmentioning

confidence: 98%

Fractional contribution of lung, nasal and gastrointestinal absorption to the systemic level following nose-only aerosol exposure in rats: a case study of 3.7-µm fluorescein aerosols

et al. 2003

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Because absorption takes place from multiple sites of aerosol deposition, it is generally difficult to interpret systemic levels following nose-only inhalation in laboratory rodents. Therefore, this study attempted to determine the fractional contribution of lung, nasal and gastrointestinal (GI) absorption to the observed systemic level following nose-only aerosol exposure in rats using fluorescein as a model powder solute. Rats were treated orally with vehicle or activated charcoal, the latter diminishing GI absorption of fluorescein, and were subsequently nose-only exposed to 3.7- micro m fluorescein aerosols at 25.2 micro g/l(air) for 10 min. While fluorescein similarly disappeared from the lung at a half-life of 0.23 hr, its plasma concentrations in the charcoal-treated group were significantly lower than those in the charcoal-untreated (vehicle) group. This suggests that significant portions of fluorescein were transported by nasopharyngeal and tracheobronchial mucociliary clearances following aerosol exposure and were absorbed from the GI tract. Despite the lack of GI absorption in the charcoal-treated animals, it was estimated that this nose-only exposure of fluorescein allowed 25.7 and 82.5 micro g/kg of simultaneous lung and nasal deposition, respectively, followed by their absorption composing the observed systemic level in this group (AUC(0- infinity ) 137.49 ng/ml h). Thus, assuming linear pharmacokinetics of fluorescein, the extent of absorption (AUC(0- infinity )) due to such nasal deposit (82.5 micro g/kg) was estimated to be 47.00 ng/ml h using the AUC(0- infinity ) obtained in an independent study of intranasal powder insufflation at 34.5 micro g/kg in the charcoal-treated rats (AUC(0- infinity ) 19.66 ng/ml h). As a result, the AUC(0- infinity ) due to 25.7 micro g/kg of the lung deposit was deconvoluted to be 90.49 ng/ml h and finally, the absolute bioavailability (F%) of the "lung-region-specific" deposition and absorption of fluorescein was estimated to be 55.0%. It is observed therefore, that lung, nasal and GI absorption accounted for 24.2, 12.5 and 63.3% of the total fluorescein absorption, respectively, following nose-only exposure of 3.7- micro m aerosols. This study addresses the common methodological insufficiency of nose-only inhalation studies in rodents, which have been neglected in most cases, and provides the appropriate kinetic interpretation for their observed systemic level.

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“…This was also quite reasonable, based on the escalator's primary regulation by cellular, adenosine 3 0 ,5 0 cyclic monophosphate-dependent phosphorylation and other, energy-dependent ciliomodulators. 30,31 Whereas IPRL viability was maintained for shortened time periods ( 60 or 120 min), passive absorption and the mucociliary escalator kinetics for F-Na were unaffected by the presence of inhibitors used in this study at 378C (Table 3). Likewise, passive absorption of the small solutes, mannitol (182 Da) and sucrose (342 Da), was reported to be unaffected by OUA (0.2-0.5 mM) in the perfusate and MON and NOC (35 mM) in the airways.…”

Section: Macromolecular Absorption and Mechanisms From The Lungmentioning

confidence: 97%