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Intezyne Technologies is an innovative and dynamic company employing a unique approach to solving the most important and complex problems associated with targeted therapeutic delivery. By integrating the fields of organic and polymer chemistry, polymer physics, materials science, biochemistry, and biology, Intezyne is well-positioned to develop new polymeric biomaterials and drug carriers that will impact the millions of people worldwide who suffer from disease. In contrast to the use of off-the-shelf polymers to develop "new" delivery technologies, Intezyne Technologies looks to design and chemically tailor novel polymers to address key problems in drug delivery. This fundamentally different strategy has led to the development of new heterobifunctional poly(ethylene glycol) (PEG) reagents and the IVECT™ drug delivery platform, a versatile system that addresses the diverse requirements for advanced drug delivery.
IVECT™ DRUG DELIVERY PLATFORM
While the design, formulation, and administration of drug delivery systems vary widely across the spectrum of drug types, the ultimate goal of targeted drug delivery is the same - deliver the ideal concentration of a therapeutic to the site of disease while minimizing side effects to healthy cells and tissue. Most modern drug delivery systems are specifically tailored to deliver a single drug type or attempt to address only a few of the difficult problems associated with targeting therapeutic delivery. Utilizing expertise in organic and polymer chemistry, Intezyne has taken a fundamentally different, bottom-up approach to addressing the most pressing deficiencies associated with currently available drug carriers. Through the rational design and chemical tailoring of new polymer materials, Intezyne has developed the IVECT™ drug delivery platform (DDP) to make targeted drug delivery a reality, improving the lives of people who suffer from disease and offering enhanced product value for our potential pharmaceutical partners.
The foundation of the IVECT™ platform is based on polymer micelle technology, spherical nanosized capsules formed by the assembly of block copolymers in water. Since drug-loaded polymer micelles typically possess diameters ranging from 20 - 200 nm, they exhibit dramatically increased circulation time when compared to stand-alone drugs due to minimized renal clearance. This feature of polymer micelles also leads to selective accumulation in cancerous tissue due to the enhanced permeation and retention (EPR) effect, a result of increased permeability to polymer micelles due to the disorganized nature of the tumor vasculature.
While simple diblock copolymer micelles are currently under development for drug delivery applications, these structures are often unstable and "fall apart" following injection as a result of in vivo dilution or interaction with destabilizing blood components. This instability leads to premature drug release outside the targeted region, resulting in minimal therapeutic value and increased toxicity to healthy cells and tissue. In addition, polymer micelles and other types of drug carriers often lack strategies for active cell targeting, a powerful technique which permits the selective attachment of the delivery system to diseased areas in the body using cell-specific ligands located on the surface of carrier.
In contrast to these simple block copolymer micelles, the IVECT™ DDP, utilizes a multi-block copolymer design, where each segment, or block, of the carrier has been tailored to address the most critical issues facing targeted drug delivery. These include expanding the range and efficiency of drug encapsulation, providing greatly enhanced in vivo stability, and targeting therapeutic release specifically in diseased cells and tissue.
- The encapsulation block can be chemically manipulated to accommodate a wide range of therapeutics and diagnostic agents such as hydrophobic and hydrophilic small molecule drugs (traditional therapeutics), proteins, DNA/RNA, and contrast agents for medical imaging. Encapsulating therapeutics in the core of the IVECT™ DDP dramatically improves water solubility and protects the therapeutic from excretion or inactivation by the body's natural defense mechanisms.
- The responsive stabilizer is the centerpiece of the IVECT™ DDP and acts to temporarily "lock" the micelle, enhancing the stability of the polymer micelle after injection. This unique functionality protects the drug in the core of the micelle and prevents premature leakage during circulation. The stabilizer has been chemically tuned to "unlock" and release the drug in diseased tissue or upon entry into diseased cells.
- The water-soluble block is made using Intezyne's heterobifunctional PEG technology and imparts micellar solubility in the body. PEG has been shown to increase the circulation lifetime of drug delivery systems while lowering cytotoxicity and auto-immune responses. This segment also contains reactive functionality presented at the micelle surface, which is utilized for the attachment of a wide array of cell-targeting groups. Targeting group attachment enables the specific accumulation of the drug in diseased tissue and/or entry into diseased cells through endocytotic pathways.
While the IVECT™ platform has been specifically designed to address the delivery needs of a wide range of pharmaceutical compounds that span a number of different drug classes, Intezyne has focused initial product development on the encapsulation and targeted delivery of off-patent, hydrophobic chemotherapeutics (e.g. doxorubicin, camptothecin, and paclitaxel) for application in various areas of oncology. By utilizing the IVECT™ platform in conjunction with these potent chemotherapeutic agents, Intezyne Technologies is working towards addressing long-standing clinical problems such as post-injection micelle stability and the targeted delivery of encapsulated therapeutics to cancer cells. Cancer-specific drug targeting using the IVECT™ platform will have a clear impact on the well-being of the many thousands of people who rely on traditional small molecule therapeutics for the treatment of cancer, offering more effective treatment options while minimizing the harmful side effects commonly observed with these chemotherapies.
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