Improvement of Intranasal Drug Delivery with Intravail Alkylsaccharide Excipient as a Mucosal Absorption Enhancer Aiding in the Treatment of Conditions of the Central Nervous System.

Intranasal drug administration is a commonly used route for therapeutic formulations, but there may be challenges associated with a lack of absorption and bioavailability, as well as damage to mucosal tissue. To address these issues, potential absorption enhancers that are generally nonirritating to nasal mucosal tissue have been investigated as excipients in intranasal formulations. Among those studied are alkylsaccharides, which are composed of sugars covalently coupled to at least one alkyl chain.

Alkylsaccharides: circumventing oxidative damage to biotherapeutics caused by polyoxyethylene-based surfactants.

Polysorbates and other polyoxyethylene-based surfactants are incorporated into most biotherapeutics to prevent protein aggregation in order to minimize loss of efficacy, induction of unwanted immunogenicity, altered pharmacokinetics and reduced shelf life. While they are effective in initially preventing protein aggregation, they contain ether linkages (within polyoxyethylene moieties) and in the case of polysorbate 80 unsaturated alkyl chains that spontaneously and rapidly auto-oxidize in aqueous solution to protein-damaging peroxides, epoxy acids and reactive aldehydes, including formaldehyde and acetaldehyde. Oxidative damage induces unwanted immunogenicity and in some instances promotes re-aggregation.

High efficiency intranasal drug delivery using Intravail® alkylsaccharide absorption enhancers.

A new class of alkylsaccharide transmucosal delivery enhancement agents are described that overcome the principal limitations preventing broad acceptance of intranasal administration for many potential applications in systemic drug delivery, namely, poor transmucosal absorption and damage to the nasal mucosa. This review will describe recent developments in use of these excipients in human clinical trials and preclinical studies along with their chemical and pharmacological properties and explore commercial implications of the use of these excipients in introduction of new intranasal formulations of peptidic and nonpeptidic drugs.

Oral delivery of octreotide acetate in Intravail® improves uptake, half-life, and bioavailability over subcutaneous administration in male Swiss webster mice.

The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogs. Octreotide acetate is a synthetic analog of somatostatin, with similar effects but a prolonged duration of action. Octreotide acetate is routinely given by subcutaneous (s.

n-Dodecyl-β-D-maltoside inhibits aggregation of human interferon-β-1b and reduces its immunogenicity.

The development of neutralizing antibodies to the protein drug interferon-β is a significant impediment to its use in the treatment of multiple sclerosis. Neutralizing antibodies to interferon-β arise from aggregation of the peptide during manufacturing and storage. We tested the ability of dodecylmaltoside, a nontoxic alkylsaccharide surfactant, to reduce aggregation of interferon-β in vitro and to reduce its immunogenicity in vivo.

Intravail: highly effective intranasal delivery of peptide and protein drugs.

Recent development of a new class of patented alkylsaccharide transmucosal delivery enhancement agents, collectively designated as Intravail (Aegis Therapeutics) absorption enhancers, has created opportunities for new therapeutic options across a broad spectrum of human diseases. Intravail absorption enhancers provide unsurpassed intranasal bioavailabilities, comparable to those that are achieved by injection for protein, peptide and other macromolecular therapeutics. These novel, highly effective and non-irritating excipients circumvent the two primary limitations of intranasal drug delivery, namely mucosal irritation and poor bioavailability, and offer the promise of more convenient, more effective and safer therapeutics for patients and physicians alike.

Structural pharmacogenomics, drug resistance and the design of anti-infective super-drugs.

Large-scale comparative analysis of drug-target polymorphism structures enables the rational design of next generation 'super drugs'--drugs that are less prone to development of drug resistance or that work for the largest possible fraction of the patient population. Furthermore, knowledge of the drug-target-shape repertoire that exists within the patient population enables predictions of likely clinical trial outcomes and response rates for drug efficacy. This gives information on the optimal drug candidates before the initiation of clinical trials.