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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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CsA = cyclosporin A; dDAVP = 1-deamino-8-D-arginine vasopressin; DPI = dry-powder inhaler; FSH = follicle-stimulating hormone; hGH = human growth hormone; MDI = metered-dose inhaler; MMAD = mass median aerodynamic diameter; PTH = parathyroid hormone; r-Con-IFN = recombinant-methionyl interferon consensus; r-huG-CSF = recombinant-methionyl human granulocyte colony-stimulating factor; TI = technosphere-insulin formulation; TSH = thyroid-stimulating hormone.Available online http://respiratory-research.com/content/2/4/198 IntroductionThe techniques of recombinant DNA technology have been well refined during the past 20 years such that it is now possible to produce, under good manufacturing practice conditions, commercial quantities of therapeutic peptides and proteins. It is expected that, during the next decade, an even greater number of molecular targets will be identified for treatment of various diseases. These are exciting developments, not only for scientists, but also for patients, because such biotherapeutic agents are very specific in their actions, and thus will greatly improve the quality of life for the majority of patients.Hundreds of bioengineered proteins and peptides are either already on the market or are undergoing clinical investigation; these include growth factors, hormones, monoclonal antibodies, cytokines and anti-infective agents, among others. However, these compounds have unusual characteristics that present considerable challenges to formulation scientists. The combination of their large molecular size, hydrophilicity and lability (both chemical and enzymatic) virtually exclude their formulation in traditional dosage forms such as tablets and capsules. Consequently, most proteins and peptides currently on the market are injectable. AbstractThe large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung that can facilitate systemic delivery via pulmonary administration of peptides and proteins. Physical and biochemical barriers, lack of optimal dosage forms and delivery devices limit the systemic delivery of biotherapeutic agents by inhalation. Current efforts to overcome these difficulties in order to deliver metabolic hormones (insulin, calcitonin, thyroid-stimulating hormone [TSH], follicle-stimulating hormone [FSH] and growth hormones) systemically, to induce systemic responses (immunoglobulins, cyclosporin A [CsA], recombinantmethionyl human granulocyte colony-stimulating factor [r-huG-CSF], pancreatic islet autoantigen) and to modulate other biological processes via the lung are reviewed. Safety aspects of pulmonary peptide and protein administration are also discussed.

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