The Nasal Mucociliary Clearance: Relevance to Nasal Drug Delivery

Mucociliary clearance is an important physiological defense mechanism of the respiratory tract to protect the body against noxious inhaled materials. This process is responsible for the rapid clearance of nasally administered drugs from the nasal cavity to the nasopharynx, thereby interfering with the absorption of drugs following intranasal application. This review describes the mucociliary system and the methods used for its characterization. Examples are given of the effects of drugs and additives on its functioning. Further, possible approaches are presented for increasing the residence time of drugs in the nasal cavity, thereby improving intranasal drug delivery.

[1]  N. G. Toremalm,et al.  A method for standardized studies of mucociliary activity. , 1974, Acta oto-laryngologica.

[2]  K. Uekama,et al.  Cyclodextrins in drug carrier systems. , 1987, Critical reviews in therapeutic drug carrier systems.

[3]  L. Allegra,et al.  Simple and precise method for counting ciliary beats directly from the TV monitor screen. , 1986, Journal of pharmacological methods.

[4]  D. Eshel,et al.  Spectral characterization of ciliary beating: variations of frequency with time. , 1985, The American journal of physiology.

[5]  R. Guillerm,et al.  Discussion on smoke and mucociliary transport. , 1985, European journal of respiratory diseases. Supplement.

[6]  F. Merkus,et al.  Nasal absorption of 17-beta-estradiol and progesterone from a dimethyl-cyclodextrin inclusion formulation in rats , 1990 .

[7]  Y. Chien,et al.  Nasal systemic drug delivery , 1989 .

[8]  P. Edman,et al.  Characterization of degradable starch microspheres as a nasal delivery system for drugs , 1990 .

[9]  M. Boysen The surface structure of the human nasal mucosa , 1982, Virchows Archiv. B, Cell pathology including molecular pathology.

[10]  K. Lloyd,et al.  A NEW EX VIVO METHOD FOR THE STUDY OF NASAL DROPS ON CILIARY FUNCTION , 1989, Fundamental & clinical pharmacology.

[11]  C. Marriott The viscoelastic nature of mucus secretion. , 1981, Chest.

[12]  J. Zuidema,et al.  The effects of preservatives on the ciliary beat frequency of chicken embryo tracheas. , 1980, Rhinology.

[13]  Hans Bisgaard,et al.  Bioadhesive microspheres as a potential nasal drug delivery system , 1987 .

[14]  I. Andersen,et al.  Measurement of nasal mucociliary clearance. , 1983, European journal of respiratory diseases. Supplement.

[15]  H. Wagner,et al.  Measurement of mucociliary function in man. , 1969, The American review of respiratory disease.

[16]  S. Lethagen,et al.  Effect of viscosity on the pharmacokinetics and biological response to intranasal desmopressin. , 1989, Journal of pharmaceutical sciences.

[17]  D. Pavia,et al.  Drug effects on mucociliary function. , 1983, European journal of respiratory diseases. Supplement.

[18]  Masaki Yamasaki,et al.  Inclusi on complexations of steroid hormones with cyclodextrins in water and in solid phase , 1982 .

[19]  H. Hansson,et al.  Structural and functional aspects of cells in the nasal mucociliary system. , 1984, Archives of otolaryngology.

[20]  D. Passali,et al.  Normal values of mucociliary transport time in young subjects. , 1985, International journal of pediatric otorhinolaryngology.

[21]  A. Silberberg On mucociliary transport. , 1990, Biorheology.

[22]  H. Wagner,et al.  Mucociliary Function during Experimentally Induced Rhinovirus Infection in Man , 1973, The Annals of otology, rhinology, and laryngology.

[23]  U. Mercke,et al.  A method for evaluating the effect of pharmacological substances on mucociliary activity in vivo. , 1982, Acta oto-laryngologica.

[24]  G. Duchateau,et al.  Correlation between nasal ciliary beat frequency and mucus transport rate in volunteers , 1985, The Laryngoscope.

[25]  K. Takeuchi,et al.  Rheological Properties of Middle Ear Effusions from Children with Otitis Media with Effusion , 1986, The Annals of otology, rhinology & laryngology. Supplement.

[26]  J. Zuidema,et al.  The effects of drugs on ciliary motility III. Local anaesthetics and anti-allergic drugs , 1982 .

[27]  J. Zuidema,et al.  The effects of nasal drops and their additives on human nasal mucociliary clearance. , 1982, Rhinology.

[28]  J. Hardy,et al.  Intranasal drug delivery by spray and drops , 1985, The Journal of pharmacy and pharmacology.

[29]  F. Merkus,et al.  The Influence of Drugs on Nasal Ciliary Movement , 1987, Pharmaceutical Research.

[30]  R. Rylander,et al.  Frequency of Ciliary Beat measured with a Photo-sensitive Cell , 1962, Nature.

[31]  K Morimoto,et al.  Enhancement of nasal absorption of insulin and calcitonin using polyacrylic acid gel , 1985, The Journal of pharmacy and pharmacology.

[32]  J. Flier,et al.  Effects of sodium taurodihydrofusidate on nasal absorption of insulin in sheep. , 1987, Journal of pharmaceutical sciences.

[33]  I. Nilsson,et al.  Intranasal administration of peptides: nasal deposition, biological response, and absorption of desmopressin. , 1986, Journal of pharmaceutical sciences.

[34]  G. P. Martin,et al.  The Effect of Some Preservatives Used in Nasal Preparations on Mucociliary Clearance , 1989, The Journal of pharmacy and pharmacology.

[35]  K. Takeuchi,et al.  Nasal mucociliary clearance in Sjögren's syndrome. Dissociation in flow between sol and gel layers. , 1989, Acta oto-laryngologica.

[36]  P. Cole,et al.  Nasal mucociliary clearance and ciliary beat frequency in cystic fibrosis compared with sinusitis and bronchiectasis. , 1981, Thorax.

[37]  P. Verdugo,et al.  Ciliary activity by laser light-scattering spectroscopy , 1977, Annals of Biomedical Engineering.

[38]  G. Duchateau,et al.  Bile salts and intranasal drug absorption , 1986 .

[39]  F. Merkus,et al.  Absorption Enhancing Effect of Cyclodextrins on Intranasally Administered Insulin in Rats , 1991, Pharmaceutical Research.

[40]  K. Takeuchi,et al.  The effect of an orally administered proteolytic enzyme on the elasticity and viscosity of nasal mucus , 2004, Archives of oto-rhino-laryngology.

[41]  P. Satir,et al.  The physiology of cilia and mucociliary interactions. , 1990, Annual review of physiology.

[42]  G. T. Yates,et al.  On the mechanics of mucociliary flows. III. Flow-velocity profiles in frog palate mucus. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[43]  J. Zuidema,et al.  The effects of nasal drops on the ciliary beat frequency of chicken embryo tracheas. , 1981, Rhinology.

[44]  F. Merkus,et al.  Intranasal estradiol administration to oophorectomized women. , 1991, European journal of obstetrics, gynecology, and reproductive biology.

[45]  G. P. Martin,et al.  The Effect of Some Preservatives Used in Nasal Preparations on the Mucus and Ciliary Components of Mucociliary Clearance , 1990, The Journal of pharmacy and pharmacology.

[46]  H. Simon,et al.  Messung Des Schleimhauttransportes in Menschlichen Nase Mit 51Cr Markierten Harzkügelchen , 1977 .

[47]  K. Adler,et al.  Physical properties of sputum. VII. Rheologic properties and mucociliary transport. , 1975, The American review of respiratory disease.

[48]  M. J. Dulfano,et al.  Effect of pH, viscosity and ionic-strength changes on ciliary beating frequency of human bronchial explants. , 1983, Clinical science.

[49]  I. Gonda,et al.  Model of Disposition of Drugs Administered into the Human Nasal Cavity , 2004, Pharmaceutical Research.

[50]  S. Saida,et al.  Interaction between mucociliary transport and the ciliary beat of chicken nasal mucosa , 2004, Archives of oto-rhino-laryngology.

[51]  A. Secchi,et al.  Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects. , 1982, British medical journal.

[52]  D. Passali,et al.  Experiences in the determination of nasal mucociliary transport time. , 1984, Acta oto-laryngologica.

[53]  J. Zahm,et al.  Influence of rheological properties of human bronchial secretions on the ciliary beat frequency. , 1984, Biorheology.

[54]  F. Merkus,et al.  Nasal Absorption Enhancement of 17β-Estradiol by Dimethyl-β-Cyclodextrin in Rabbits and Rats , 1990, Pharmaceutical Research.

[55]  D. L. Patterson,et al.  Frog Palate Mucociliary Apparatus: Structure, Function, and Response to Formaldehyde Gas , 1984 .

[56]  Nagai Tsuneji,et al.  Powder dosage form of insulin for nasal administration , 1984 .

[57]  Clive G. Wilson,et al.  The influence of solution viscosity on nasal spray deposition and clearance , 1988 .

[58]  F. Aoki,et al.  Distribution and removal of human serum albumin-technetium 99m instilled intranasally. , 1976, British journal of clinical pharmacology.

[59]  F. Merkus,et al.  Absorption Enhancement of Intranasally Administered Insulin by Sodium Taurodihydrofusidate (STDHF) in Rabbits and Rats , 1989, Pharmaceutical Research.

[60]  S. Davis,et al.  Nasal administration of gentamicin using a novel microsphere delivery system , 1988 .

[61]  J Yager,et al.  Measurement of frequency of ciliary beats of human respiratory epithelium. , 1978, Chest.

[62]  J. Zahm,et al.  Role of mucus and cilia in nasal mucociliary clearance in healthy subjects. , 1989, The American review of respiratory disease.

[63]  A. Wanner Clinical aspects of mucociliary transport. , 1977, The American review of respiratory disease.

[64]  S. Gizurarson,et al.  Animal models for intranasal drug delivery studies. A review article. , 1990, Acta pharmaceutica Nordica.

[65]  Y. Majima,et al.  Nasal mucociliary clearance under various conditions. , 1983, Acta oto-laryngologica.

[66]  E. Puchelle,et al.  Comparison of three methods for measuring nasal mucociliary clearance in man. , 1981, Acta oto-laryngologica.

[67]  F. Merkus,et al.  Effects of Absorption Enhancers on Human Nasal Tissue Ciliary Movement in Vitro , 1990, Pharmaceutical Research.

[68]  Lisbeth Illum,et al.  Nasal administration of insulin using bioadhesive microspheres as a delivery system , 1990 .

[69]  D. R. Adams,et al.  Transitional epithelial zone of the bovine nasal mucosa. , 1986, The American journal of anatomy.

[70]  Y. Takatsuka,et al.  Mechanisms for the enhancement of the nasal absorption of insulin by surfactants , 1981 .

[71]  J. Zuidema,et al.  The influence of the pH and osmotic pressure upon tracheal ciliary beat frequency as determined with a new photo-electric registration device. , 1980, Rhinology.

[72]  S. Lethagen,et al.  Effect of viscosity on particle size, deposition, and clearance of nasal delivery systems containing desmopressin. , 1988, Journal of pharmaceutical sciences.

[73]  G. P. Martin,et al.  Direct effect of bile salts and phospholipids on the physical properties of mucus. , 1978, Gut.

[74]  R. L. G. Kirsner,et al.  Measurement ofin vitro ciliary beat frequency: A television-video modification of the transmitted light technique , 1986, Medical and Biological Engineering and Computing.

[75]  D. Yeates,et al.  Stimulation of ciliary beat frequency by autonomic agonists: in vivo. , 1988, Journal of applied physiology.