Propofol Microemulsions Pre-clinical Investigation

Nanomedex, Inc., Fitchburg WI

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Domestic propofol sales exceed $500 million annually and continue to increase due to a shift towards ambulatory surgery. This intravenous anesthetic exists as an oil and necessitates dispersion in a soybean macroemulsion (i.e., Intralipid). This formulation (e.g., Diprivan) has a number of disadvantages overcome with a microemulsion formulation. The present investigators hypothesize that the lipophilicity of propofol can be leveraged to construct oil-in-water microemulsions in which propofol serves dual roles as both the active pharmaceutical and the core oil component of the nanoparticles. Furthermore, the investigators hypothesize that the relaxation constant of the microemulsion can be modified so that nanoparticles reach the central circulation before releasing active drug to cause general anesthesia. Three specific aims are proposed herein to test the feasibility of this approach. Specific Aim 1: Synthesize microemulsion-based nanoparticle systems of propofol with varying concentrations of biologically-friendly surfactants (proprietary information, see B.5) in order to modify the relaxation rate of the nanoparticles and, thereby, drug release rate and time to cause general anesthesia. Specific Aim 2: Using a randomized, crossover design in dog and rat, demonstrate that propofol-based nanoparticles causes general anesthesia and pharmacokinetic indices similar to that caused by a commercially available formulation (e.g., Diprivan), but without associated pain on injection. Specific Aim 3: In dog, conduct a preliminary safety investigation emphasizing possible effects on hemolysis and coagulation as assessed by thromboelastography. Although the specific aims are sharply focused, this technology is applicable to a broad number of lipophilic pharmaceuticals. The goals allude to the possibility of using nanoparticles to infuse caustic or lipophilic drugs previously reserved for central venous catheters via a peripheral intravenous cannula. In addition, these objectives integrate well into the core competency of NanoMedex, Inc. to disperse lipophilic drugs using nanotechnology and into NanoMedex's business strategy wherein all nanoparticle constituents are currently off patent and previously intravenously infused into humans.