Intravail®
Transmucosal Absorption Enhancers

ProTek®
Protein and Peptide Stabilization Excipients

Aegis Hydrogels™
Absorption-enhancing self-assembling non-polymeric hydrogels



Intravail® Technology
Intravail® comprises a broad class of chemically synthesizable transmucosal absorption enhancement agents that allow non-invasive systemic delivery of potent peptide, protein, nucleotide-related, and other small and large molecule drugs that were previously only deliverable by injection.

Intravail® is Safe
Aegis’ Intravail® absorption enhancement agents are mild and non-irritating to mucosal membranes. They are safe, odorless, tasteless, non-toxic, non-irritating, nondenaturing, and non-mutagenic, chemically synthesized molecules that metabolize to CO2 and H2O. These molecules are closely related to mild surfactants widely used in personal care and food products in significantly higher concentrations than those used in Aegis formulations and are recognized as GRAS substances for many applications.

Intravail® is Effective
Intravail® absorption enhancement agents provide exceptionally high and unmatched bioavailability performance, comparable in efficiency to subcutaneous injection, via the intranasal, buccal, intestinal, and other mucosal membrane administration routes, delivering potent peptide, protein, and large molecule drugs that can currently only be delivered by injection (See Figure 1).

 

Intravail® is Broadly Applicable

We have proven feasibility for a broad range of therapeutics up to 30,000 Daltons molecular weight including calcitonin, growth hormone, leptin, PTH, insulin, erythropoietin, PYY-3-36, GLP-1 related peptides, glucagon, anti-sense drugs, and low molecular weight heparins. While our primary focus is on the intranasal application of Intravail® , the technology can also dramatically improve the bioavailability of therapeutics through any of the following modes of administration:

• Intranasal
• Ocular
• Oral & Oral Cavity
• Pulmonary
• Rectal
• Transdermal
• Vaginal
  
  

Intravail® is Simple to Use

Intravail® technology is compatible with simple off-the-shelf nasal spray delivery devices and standard homogeneous manufacturing formulation and dispensing processes – no particles, powders, liposomes, or chemical modifications, and no need for complicated and expensive dispensers requiring patient training. Our customers are not required to invest in any special manufacturing equipment or delivery devices.

Intravail® is Good Business

Creation of intranasal formulations of existing injectable products provides access to new and expanded markets, broader clinical applications of existing therapeutics, and greater patient convenience and acceptance. Confirming this, sales of nasally-delivered therapeutics have demonstrated 5- to 33-fold increases in sales over the original equivalent injectable formulation. New non-invasive formulations of existing peptide and protein therapeutics can provide opportunities for maximizing value extraction from an existing drug franchise and will allow for patent life extension and product life-cycle management. With a reported 600 - 700 peptide therapeutics in clinical or preclinical development (Frost & Sullivan) non-invasive Intravail® -based formulations of new peptide or protein drugs will facilitate market introduction of “first in class” therapeutics, capitalizing upon the growing trend toward broad-scale acceptance of peptide drugs.

Summary of Intravail® Properties and Benefits:     

• Mild and non-irritating to mucosal membranes      
• Exceptionally high and unmatched bioavailability - comparable in efficiency to subcutaneous injection, via the intranasal administration route
• Delivery of potent peptide, protein, and large molecule drugs that can currently only be delivered by injection
• No alteration of the chemical form or biological integrity of the drug – i.e., no liposomes particles, pumps, patches or emulsions
• Rapid drug absorption and onset of action
• Controlled transient permeation of the nasal mucosal barrier
• Avoidance of gastric hydrolysis and “first pass effect” elimination
• Greater patient convenience and compliance
• Elimination of needle-stick injuries and associated transmission of blood-borne pathogens
• Compatibility with current nasal delivery devices
• Ease of formulation and compatibility with routine homogeneous formulation and dispensing manufacturing processes for ease of scale-up and production
• Extension of patent protection and product life-cycle
• Broadly applicable to other transmucosal and transdermal administration routes
  

ProTek® Technology

Aegis’ ProTek® protein stabilization technology comprises the use of proprietary GRAS excipients that prevent aggregation of proteins and peptides thereby stabilizing them and reducing immunogenicity. ProTek® allows creation of proprietary, easily manufacturable, homogeneous, stable, aqueous or lyophilized dosage forms for peptide or protein therapeutics that maintain the structural integrity and physiological activity of many protein and peptide drugs. ProTek® formulations are applicable to injectable, intranasal, and other dosage forms. ProTek® excipients may also be incorporated into manufacturing processes requiring producing or manipulating concentrated protein or peptide solutions which result in unwanted or irreversible aggregation.

Figure 2 demonstrates the long-term prevention of human insulin denaturation at elevated temperature upon continuous agitation at 150 rpm, 37ºC. Light scattering, a quantitative measure of solution cloudiness arising upon denaturation, was monitored over a period of 60 days in this particular study. Bioassay confirms the loss of activity in the absence of ProTek® excipient. Without inclusion of a ProTek® excipient, insulin becomes perceptibly cloudy in a matter of hours under these stressing conditions. The stabilization effect is even more dramatic at pH values below pH 7 where insulin in completely denatured in two days or less in the absence of ProTek® excipient. Complete stabilization has been demonstrated to continue for up to three months of continuous shaking at 37ºC. Structurally related non-ProTek® alkylsaccharides fail to provide similar protection as shown by the controls.

Aegis Hydrogel™ Technology

Aegis Hydrogels™ are proprietary absorption-enhancing self-assembling aqueous hydrogels useful for transdermal drug delivery, or for transmucosal applications benefiting from extended residence time. Aegis Hydrogels™ serve simultaneously as both delivery vehicle and absorption enhancer. In dermal applications, these hydrogels leave the skin feeling soft with no sense of any residue when rubbed onto the skin. In dispensing applications, including depot or sustained release applications, the thixotropic nature of these gels prevent dripping or running and allows resumption of the stable gel form as soon as the shear force of dispensing terminates.