Page 1 Development of Pristina TM Aerogel for Targeted and Controlled Release of Cancer Pharmaceuticals The ATTIA Applied Sciences Inc. TAASI Corporation
Page 2 Schematic of Therapeutic Nanodevice A) Particle device binds to target cell. B) Therapeutic agent is released from pore structure of device. Aerogel Particle Target Cell Cell Membrane Receptor on cell surface Ligand “Stealth” Coating Aerogel Particle Agent Releasing Target Cell Near Cell Cell Wall Agent Receptor
Page 3 TAASI Project Goals 1. Develop very fine particles [less than 2 microns] with 90% porosity of TAASI’s Pristina TM SCM-Aerogel for the storage and subsequent 60 minute controlled release of targeted pharmaceutical agents (melitin). 2. Integrate the chemical “o,o-Bis{3- aminopropyl) polyethylene glycol”, which acts as the “stealth” & anchoring link to the tumor specific EGF (Epidermal Growth Factor Ligand) protein. 3. Gadolinium Oxide, Gd2O3 [gadolinia], to be incorporated into the aerogel to act as a detection tag/identification label.
Page 4 Evaluation Procedures: Aerogel Effectiveness for Targeted/Controlled Release Pharmaceuticals Routine experiments were outsourced to determine the effectiveness of the TAASI Aerogel particles in the melitin delivery system to targeted Cancer cells. Aerogel Particle Preparatory Methods o Coupled with EGF (Epidermal Growth Factor Ligand) and loaded with melitin prior to “seek and destroy” experiment Model of Cancer Cells: Swiss 3T3 Cells o Expresses high levels of EGF Receptors Model of Non-Cancer Cells: CHO Cells o Cell concentration was adjusted to equal the Swiss 3T3 o No EGF Receptors Present on CHO cells
Page 5 TAASI Microgel SCM-PEG-Gd Aerogel
Page 6 Size Reduction Methods 1. Micronization, by Sonication, was used to achieve the desired aerogel particle size of 1 to 2 microns. 1. Fractionation, by gravity settling, was use to separate out the desired aerogel particles.
Page 7 TAASI Microgel SCM-Gd Size Distribution: Unsonicated vs. Sonicated Page 7 Particle size distribution data (Coulter Multisizer) for Sonicated and Unsonicated aerogel particles
Page 8 TAASI Aerogel Property Results MaterialDensity g/cc Porosity % BET m2/g SCM-A A: SCM-Gd-PEG* D: SCM-Gd (NO PEG) Abbreviation Key 1.SCM: TAASI Propriety Information 2.A: Autoclaved 3.Gd: Gadolinium Oxide 4.PEG: Polyethylene Glycol * Used in ‘Seek & Destroy’ Control Release Therapy
Page 9 Melitin Release Comparison: Pristina™ 2A-SCM Aerogel & Aldrich Silica Page 9
Page 10 Death Loss of CHO & Swiss 3T3 Cells: Raw Data from Flow Cytometry Experiment Page 10 CHO CellsSwiss 3T3 Cells Flow Cytometry preformed by Kristie Melnik 1% Dead 97% Dead
Death Loss of Swiss 3T3 and CHO Cells Page 11 % Dead