SBIR Phase I: Lipoleosomes as Carriers for Topical Ibuprofen

This SBIR Phase I project addresses a critical need in medicine ? the ability to deliver drugs selectively to parts of the body that need medication. Targeted drug delivery improves patient outcomes by treating tissues locally while reducing overall exposure and side effects elsewhere. For example, a cream or lotion type product which moves anti-inflammatory drugs through skin specifically to an affected joint is better than taking a pill which medicates the entire body. Nanoparticles, especially liposomes (nanometer size water balloons consisting of a fatty wall surrounding an aqueous interior) are useful for targeted drug delivery because of their ability to move through biological barriers including skin. Unfortunately, use of liposomes is limited because the drug carrying capacity is too small, especially for water insoluble drugs. Lipoleosomes are a new type of liposome with a much greater carrying capacity for drugs. The objective of this project is to make lipoleosomes with ibuprofen, a water-insoluble drug and demonstrate the ability to move ibuprofen through skin for localized treatment of joints and muscles. This will be valuable for developing a lotion product to treat arthritis and injuries while avoiding stomach problems. The creation of lipoleosomes resulted from a remarkable discovery ? that under certain conditions, flat fatty layers (lipid bilayers) existing in microemulsions can be reshaped by hydration into spherical liposome form. Because microemulsion lipid bilayers can contain large amounts of water-insoluble (hydrophobic) compounds (easily up to 65%), so can the product liposomes. Previously, hydrophobic drug content of liposomes rarely exceeded 5%. In light of the extraordinarily greater drug capacity, the new liposomes were named lipoleosomes, indicating a liposome into which organic compounds (oleo) have been inserted. It is a scientific curiosity that some microemulsion lipid layers reshape to give membrane structures because in the past, hydration had only been known to give filled emulsion droplets which do not have the important biological features of liposomes. In this project, the quality and yield of lipoleosomes and their biological characteristics will be improved by understanding the influence of precursor microemulsion properties and processing conditions. This will result in the availability of new, biologically effective lipoleosomal ibuprofen compositions and methods of synthesis, plus physical and biometric data that supports submission of a new drug application for a topical ibuprofen lotion or cream. Establishing lipoleosomes as a new type of nanoparticle has implications for many other drugs and for routes of administration other than dermal.