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Reformulation of Cancer Therapeutics using Nanotechnology



The design of novel therapies and drug delivery systems for cancer is being enabled by nanotechnology. Nanoscale devices carrying therapeutic payloads and delivered within close proximity of the tumor in vivo will play a significant role in increasing the effectiveness of the treatment while decreasing severity of side effects. Such techniques would be highly relevant, particularly for organs that are difficult to access because of a variety of biological barriers, including those developed by tumors. The successful delivery of well established chemotherapeutics using nanoparticle-based delivery platforms has previously been demonstrated; however, an even bigger opportunity that can be enabled by nanoparticle delivery is the potential to mitigate the adverse properties of once promising drugs which failed to reach clinical trials or failed in clinical trials due to excessive toxicity and can be reformulated into safe and viable therapies using nanoparticles. Furthermore, poor oral bioavailability, poor solubility in biological fluids, inappropriate pharmacokinetics, and lack of efficacy within a tolerable dose range can be also addressed using such reformulation approaches.

To accelerate such efforts, the National Cancer Institute (NCI) requests proposals for the development of commercially-viable nanotechnology-based platforms for the reformulation of cancer therapeutics.

Project Goals:

The goal of this project is to identify and evaluate the potential of candidate nanotechnologies to significantly improve the performance of anti-cancer agents. Specifically, this topic is intended to fund nanotechnology delivery systems which will enable anti-cancer drugs which could not otherwise be delivered in free form due to their excessive toxicity, poor oral bioavailability, poor solubility in biological fluids, inappropriate pharmacokinetics, and lack of efficacy within a tolerable dose range to be re-examined as potential therapies for cancer treatment. Drug-nanoparticle constructs must yield a significant improvement in properties with respect to the free drug and FDA-approved formulations of the drug. Of special interest are drug-nanoparticle constructs which mitigate the unacceptable properties of the drugs which may not currently be administered to humans in free form.

These drug-nanoparticle constructs can take, for example, the form of multi-functional targeted nanoparticles or multi-chamber chips carrying encapsulated drugs. Further, the drug-nanoparticle constructs may also utilize imaging agents for a combination of therapeutic and diagnostic modalities that aim to provide real-time feedback and monitoring of therapy. They may include, but are not limited to the following:

·       novel therapeutic nanodevices

·       devices involving novel tumor targeting and concentrations schemes

·       novel drug loading and releasing schemes

·       novel therapeutic or theranostic nanodevices which are able to cross the blood-brain barrier

Offerors must identify the drug which they intend to reformulate for this topic. Offerors must also cite at least one clinical trial, one paper in a respected journal or submit original data which clearly demonstrates the reason(s) which prevented the drug from receiving FDA approval or entering clinical trials. Offerors must provide evidence that they can synthesize, purchase or otherwise obtain the drug as part of their proposal in order to be eligible for this topic (i.e., Offerors are solely responsible for obtaining the drug). Intellectual property issues and material transfer agreements regarding the usage of the drug are the responsibility of the offerors. Peptides, proteins and nucleic acids are not acceptable drug candidates for this topic.

Phase I Activities and Expected Deliverables:

·       Proof-of-conceptencapsulation or attachment of undeliverable therapeutic agent to nanoparticle

·       In vitrodemonstration of nanoconstruct stability and controlled release of therapeutic agent from nanoconstruct

·       Proof-of-concept in vitro studies demonstrating efficacy in relevant cell lines

·       Proof-of-concept small animalstudies demonstrating improved therapeutic efficacy and improved therapeutic index, bioavailability, solubility, and/or pharmacokinetics as compared to the use of free drug (utilizing an appropriate animal model)

Phase II Activities and Expected Deliverables:

·       Long Term Toxicity Studies

·       Biodistribution Studies

·       Initiation of large animal studies

·       Demonstration of nanotherapeutic manufacturing and scale-up scheme

IND-enabling studies carried out in a suitable pre-clinical environment

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