Nasal delivery route

Attributed to the demand for facile and low-risk vaccine administration, the needle-free, nasal delivery routes are sought and investigated [164]. Herein, bionanocomposites prepared by a combination of fibrous clay and polysaccharides... 

Virtually all therapeutic proteins must enter the blood in order to promote a therapeutic effect. Such products must usually be administered parenterally. However, research continues on the development of non-parenteral routes which may prove more convenient, less costly and obtain improved patient compliance. Alternative potential delivery routes include transdermal, nasal, oral and bucal approaches, although most progress to date has been recorded with pulmonary-based delivery systems (Chapter 4). An inhaled insulin product ( Exubera , Chapters 4 and 11) was approved in 2006 for the treatment of type I and II diabetes. 

Parenteral administration is not perceived as a problem in the context of drugs which are administered infrequently, or as a once-off dose to a patient. However, in the case of products administered frequently/daily (e.g. insulin to diabetics), non-parenteral delivery routes would be preferred. Such routes would be more convenient, less invasive, less painful and generally would achieve better patient compliance. Alternative potential delivery routes include oral, nasal, transmucosal, transdermal or pulmonary routes. Although such routes have proven possible in the context of many drugs, routine administration of biopharmaceuticals by such means has proven to be technically challenging. Obstacles encountered include their high molecular mass, their susceptibility to enzymatic inactivation and their potential to aggregate. 

A nasal-based biopharmaceutical delivery route is considered potentially attractive as ... 

In comparison to the skin, the buccal mucosa offers higher permeability and faster onset of drug delivery, whereas the key features which help it score over the other mucosal route, the nasal delivery system, include robustness, ease of use, and avoidance of drug metabolism and degradation. The buccal mucosa and the skin have similar structures with multiple cell layers at different degrees of maturation. The buccal mucosa, however, lacks the intercellular lamellar bilayer structure found in the stratum corneum, and hence is more permeable. An additional factor contributing to the enhanced permeability is the rich blood supply in the... 

The nasal route is generating increasing interest as a route for the administration of local treatments and a cost-effective and patient-friendly alternative to injection for systemic delivery [49]. The special advantages of nasal delivery make it attractive for (i) crisis treatment where rapid onset of action is desirable (e.g., pain, migraine, panic attacks), (ii) systemic delivery of compounds that at present can only be delivered by injection (peptides/pro-proteins/vaccination), and (iii) direct targeting of the CNS (polar drugs for the treatment of CNS disorders). 

The nonperoral mucosal delivery routes such as buccal, nasal, and vaginal sites offer barriers to drug molecules similar to that of the peroral route. Drugs delivered via these routes have to be small (<300 Da), lipophilic in nature, and with low dosage regimen requirements. The different approaches used to deliver drugs across these mucosae include the use of enzyme inhibitors, penetration enhancers, bioadhesive patches, prodrugs, liposomes, and solubility modifiers.96,106,130... 

Nasal devices, such as metered-dose nasal sprays, are simple for the patient to use and might be expected to be more acceptable to the patient than the use of pessaries or suppositories for the intravaginal and rectal delivery routes respectively. 

Both the type of drug delivery system and the specific type of delivery device can affect drug absorption via the nasal route. The choice of delivery system depends mainly on the physiochemical properties of the drug, its desired site of action, and, more importantly, patient compliance and marketing aspects. The formulations most commonly used in nasal delivery are solutions, suspensions, gels, dry powders, and, most recently, nanoparticulate formulations. 

Giroux, M. (2005), Controlled Particle Dispersion Effective nasal delivery from a versatile, flexible technology platform, in Nasal Drug Delivery Rapid Onset via Convenient Route, ONdrugdelivery, pp. 13-15. 

Dry powder formulations for nasal delivery of peptides and proteins have been investigated for the first time by Nagai and others [38], Since then, much research work has been done on dry powders containing bioadhesive polymers for nasal drug administration. The bioavailability and duration of action of drugs administered by the nasal route are increased by the use of the principle of mucoadhesion and dry powder formulations. Research work on dry powder formulation containing bioadhesive polymers is summarized in Table 1. 

If the presence of a pharmacologic activity for a peptide is the only criterion for its use in therapy, then nasal administration may be employed, even though bioavailability is not 100%. However, when bioavailability, as determined by plasma level profiles, is considered, the nasal route for peptide administration is not optimal unless enhancers are employed. Enhancers may cause irritation and reduced membrane integrity. Other drawbacks of nasal delivery include the small... 

The nasal delivery of vaccines is a very attractive route of administration in terms of efficacy and consumer friendliness. A population-wide immunization against influenza has yet to be achieved. The pain of injections discourages many people from receiving a flu shot. The nasal route offers the advantage of a mucosal response followed by a seric response, and has proved to be a very efficient mode of administration. ... 

Considerations of commercial viability have likely influenced the extent of exploratory research activity on the various non-invasive delivery options available for protein and peptide delivery. Currently, the buccal/ sublingual, nasal, transdermal, pulmonary, and oral routes of administration are receiving the most attention in the scientific and patent literature with some technologies showing promise as potentially feasible commercial products. The following sections examine each of these non-invasive delivery routes in greater detail. 

Formulation and dosage form aspects that can impact the site of deposition within the nasal cavity are a key consideration for nasal delivery. The site of deposition can impact absorption due to the differences in the permeability and residence time of the anterior and posterior portions of the nose. A variety of dosage forms such as nasal drops, sprays, gels, powders, or microspheres are available for administering pharmaceuticals by the nasal route, and these options need to be carefully evaluated because the type of dosage form can impact where the formulation is deposited in the nasal cavity and, in turn, the systemic absorption. For example, the bioavailability of nasally administered desmopressin was significantly increased in a spray formulation compared with drops, " likely... 

Upon intranasal administration, a drug is not as susceptible to dilution and first-pass effects as in oral delivery.46 47 The nasal route may also be an effective means of delivering drugs to the brain 46 Barriers to nasal delivery include the enzymes of the nasal mucosa, the epithelial barrier, the mucus layer, and limited absorption time resulting from mucociliary clearance.48... 

---