SBIR Phase I: Delivery of Hydrophobic Chemotherapeutics via Laser-Initiated Nanosyringes

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The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to improve cancer patient outcomes by providing a new method of chemotherapeutic drug delivery that expands the arsenal of deliverable drugs and provides a highly potent dose, on demand, directly at the tumor site. Millions of dollars are spent on cancer drug R&D each year, but the translation of promising pre-clinical drug candidates to clinical trial success is marginal at best due to safety concerns, poor drug solubility in aqueous media, and undesirable pharmacokinetic profiles. In fact, 40% of currently marketed drugs and 90% of drugs in development can be characterized as poorly soluble. Targeted approaches that can package, protect, and then deliver insoluble drugs directly into cancer cells on demand, will accelerate the transition of cancer drugs from bench to bedside and help realize the clinical potential of the estimated $8.2B spent on developing insoluble drugs. Ultimately, this new nanocarrier solution will provide pharma companies and physicians with an extraordinary tool for accelerating towards molecular and personalized medicine with localized delivery of insoluble drugs, expanding the arsenal of solutions for successfully combating cancer.The proposed project will enable the clinical translation and targeted delivery of chemotherapeutics with poor solubility. High-throughput drug screening has enabled identification of new cancer therapeutics, many of which exhibit excellent biological therapeutic action, but suffer from poor pharmacokinetics and in vivo stability due to limited solubility in aqueous media. Proper packaging for in vivo delivery of these hydrophobic drugs represents a large unmet need for pharmaceutical companies targeting the $42B cancer chemotherapeutics market. Furthermore, even once packaged, protected in vivo, and accumulated in a tumor, many drugs require endosomal escape to the cytosol to exact their therapeutic potential. Thus, delivery to the cytosol represents another critical challenge. The proposed Laser Initiated Nanosyringe (LINs) delivery platform addresses these two challenges. LINs is an optically-triggered phase change nanocarrier platform designed to target and treat cancer by delivering hydrophobic chemotherapeutics directly to the cytosol of molecularly targeted cancer cells. The proposed research will lead to a functional prototype of LINs capable of selectively delivering the hydrophobic model drug paclitaxel directly to the cytosol of cancer cells in vitro. Ultimately, the goal is to develop a platform technology that will significantly enhance the selectivity and efficacy of many insoluble chemotherapeutic drugs under development.