Noninvasive administration

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Tab. 2 Absolute bioavailibility of proteins and peptides after noninvasive administration in comparison...

A. Paul and G. Cevc. Noninvasive administration of protein antigens transdermal immunization with the bovine serum albumin in transfersomcs. Vaccine Re.s. 4 (1995) 145. 

Insulin Bioavailability (Percent of Parenteral Availability) after Noninvasive Administration without Enhancer to Rats by Various Routes... 

Noninvasive drug delivery may require the administration of the drug delivery system (DDS) at an epithelium as a suitable site of absorption of the active compormd. Such regions are usually called mucosae. In the human body several mucosal sites can be identified, the one mostly used for administration and absorption of therapeutics being the gastrointestinal route. In order to increase the residence time at these absorption sites, a so-called mucoadhesive delivery system has to be used. Generally, these systems consist of one or more types of hydrogels. 

Topical application is the most common route of administration for ophthalmic drugs. Advantages include convenience, simplicity, noninvasive nature, and the ability of the patient to self-administer. Because of blood and aqueous losses of drug, topical medications typically do not penetrate in useful concentrations to posterior ocular structures and therefore are of no therapeutic benefit for diseases of the retina, optic nerve, and other posterior segment structures. 

B.M. Seddon, G.S. Payne, L. Simmons, R. Ruddle, R. Grimshaw, S. Tan, A. Turner, F. Raynaud, G. Flalbert, M.O. Leach, I. Judson, P. Workman, A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy, Clin. Cancer Res. 

Insulin is the protein that has been most investigated for pulmonary administration. Insulin levels are not maintained in diabetic patients, and precise control over blood glucose levels is needed. Insulin is a small protein, 5.8 kDa, which is composed of two chains that are covalently linked by an interchain disulfide bond. Currently, insulin is administered by injection, several times a day for many diabetics. The ability to deliver insulin via a noninvasive route would free diabetics from inconvenient, invasive insulin delivery methods and possibly eliminate secondary problems associated with diabetes, such as diabetic retinopathy. 

One of the main drivers for the development of new pulmonary drug delivery systems has been the potential for noninvasive systemic delivery of protein and peptide compounds. The systemic delivery of macromolecules via the airways would overcome the inconvenience and cost associated with current methods of administration (injection), and appears likely given the large surface area of the airways and the thin pulmonary epithelium. Most research has concentrated on pulmonary delivery of insulin for the treatment of diabetes. Recently, one insulin product has completed phase three studies and is now undergoing review by European regulatory agencies for marketing approval. 

Nevertheless, very limited research has been carried out to develop DDS for the posterior segment of the eye in the last decades. Whereas new antiangiogenic compounds and neurotrophic factors can open new therapeutic avenues in the treatment of AMD, retinal dystrophies and ocular manifestations of diabetes, the frequent intraocular injections of these compounds remain a problem and are associated with complications and discomfort for the patient. Thus, the need for efficient noninvasive DDS for the administration of drugs to the back of the eye is awaiting a ground-breaking multidiscipline advancement. 

Iontophoresis is a local noninvasive method of administration associated with minimal discomfort for the patient. However, this procedure can produce complications, including... 

Transdermal delivery is a noninvasive intravenous infusion of drug to maintain efficacious drug levels in the body for predictable and extended duration of activity. Diffusion-controlled transdermal systems are designed to deliver the therapeutic agent at a controlled rate from the device to and through the skin into the systemic circulation. This route of administration avoids unwanted presystemic metabolism (first-pass effect) in the GI tract and the liver. Patient satisfaction has been realized through decreased... 

Since the first introduction of insulin to treat diabetic patients in 1923, much effort has been made to seek alternative convenient and painless routes for insulin administration instead of daily injections. In this respect the pulmonary route has received the most attention, and substantial evidence has shown inhaled insulin to be an effective, well-tolerated, noninvasive alternative route [53-56]. Insulin therapy is required for patients with type 1 diabetes. Although some patients with type 2 diabetes can control their disease with oral antidiabetics, many will eventually also require insulin. Thus, inhaled insulin shows promise for type 2 diabetic patients [54, 56]. There are two principal inhalation systems for insulin, namely aqueous solution and dry powder. The dry powder form (Exubera ) has been approved by FDA and the European Medicines Agency (EMEA) in January 2006. 

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