Various routes of administration other than injection for proteins and peptides have been explored. The ability of molecules to permeate the skin effectively appears to be related to molecular size, lipid solubility and peptide protein ionization. Molecules less than 1000 daltons appear to cross the skin barriers rapidly. As molecular size increases, the permeability of the molecule decreases rapidly.
Several approaches have been utilized to improve the transport to deliver large molecules using enhancing agents in combination with protease inhibitors and biodegradable polymeric materials similarly failed to achieve therapeutic levels of proteinic drugs in the patient.
The In ParT delivery system developed by Transdermal Corp addresses the above need by providing an improved delivery of pharmaceutical compositions comprising macromolecular pharmaceutical agents, via the novel mixed micelle-forming compound in a suitable solvent. It is a novel, commercially viable transdermal non-invasive drug delivery technology that enables delivery and absorption of active compounds through the stratum corneum and throughout the skin and sub cutaneous tissue without any cutaneous toxicity
- The novel delivery system is capable of delivering proteins, peptides, hormones, vaccines or small molecule drugs. The molecular weight of the macromolecular pharmaceutical agent can range between about 1,000 and 2,000,000 daltons.
- The thearpeutic agent is presented in a mixed micellar form, with a micelle size of approximately one to 10 nanometers (nm) or higher. Nano particles are made from combinations of micelles (surfactants and protein solubilizers), coated with lipid molecules
- Nano paticles size; less than 1-10 nano meters smaller than the skin pores
- Nano Particles Physically entraps active without any changes in the chemical composition
- Stabilizes the actives: shelf stable at room temperature for extended period of time without refrigeration)
- Uses all FDA approved ingredients
The term “mixed micelles” refers to at least two different types of micelles, each of which has been formed using different micelle forming compounds; for example, the present compositions comprise a mix of at least two different types of micelles—micelles formed between the pharmaceutical agent and alkali metal alkyl sulfate, and micelles formed between the pharmaceutical agent and at least one different additional micelle forming compound. Each individual micelle can be formed from more than one micelle forming compound as well. The mixed micelles of the present invention tend to be smaller than the pores of the membranes (skin). It is therefore believed that the extremely small size of the present mixed micelles helps the encapsulated macromolecules penetrate efficiently through the skin. Thus, the present technology offers increased bioavailability of active drug, particularly across the skin, when compared with pharmaceutical preparations known in the art.
The In ParT delivery system also enhances the rate of absorption of macromolecular pharmaceutical agents comprising the agent in combination with specific combintion of absorption enhancers and at least one micelle-forming compound. The micelle encapsulates the molecule of interest and various combinations of micelle-forming compounds are utilized in order to achieve the present formulation. It is believed that the presence of the micelles significantly aids in the absorption of the macromolecular pharmaceutical agent both because of their enhanced absorption ability and also because of their size.
SEM Photographs of Mixed Micelles (nano-spheres)