GEN Exclusives

More »

Feature Articles

More »
May 15, 2009 (Vol. 29, No. 10)

Delivery Firms Focus on Efficiency & Efficacy

Administering Novel Therapeutics and Improving Drug Safety Serve as the Driving Forces

  • Drug Encapsulation

    Carigent Technologies is developing a delivery platform that allows high-density application of molecules to the surface of biodegradable, polymeric particles as well as high loading of RNAi material into FDA-approved polymers. The company’s technology, based on exclusive licenses from Yale and Cornell Universities, combines well-characterized, safe materials with a method of adhering ligands to particle surfaces at high density, thereb, allowing delivery of multiple therapeutic modalities.

    “While our polymers have been used in humans for decades, people thought you couldn’t load them with potential drugs such as oligonucleotides because of charge incompatibilities and other factors,” Seth Feuerstein, M.D., J.D., president, noted. “It turns out you can; we achieve high loading and targeted delivery due to our symbiotic technologies.”

    Carigent’s PLGA-based particles for drug loading and delivery range in size from tens of nanometers to hundreds of microns. Dr. Feuerstein said the company’s platform allows sustained release of therapeutic agents, tethering of surface ligands, targeting of therapy to a particular physiological site, and the ability to combine multiple agents into one vehicle made primarily from FDA-approved materials.

    Using its proprietary process, Carigent can encapsulate the therapeutic of interest within the polymer matrix, while attaching choice ligands to the surface using amphiphilic functional groups at high densities, according to Dr. Feuerstein. The delivery vehicles are capable of targeted delivery, internalization by cells and tissues, and sustained release of the encapsulated therapeutic over a period of days to months. 

    This combination of differentiating characteristics, he said, allows delivery of multiple therapeutic modalities such as RNAi, peptides, small molecules, and therapeutic vaccines as well as flexibility in targeting the drug delivery system for a variety of disease states and delivery routes and enhanced in vivo circulation times.

    Dr. Feuerstein, in referring specifically to the significant challenge of siRNA therapeutics delivery, said lead delivery programs have, for the most part, revolved around lipid-derived and/or cationic delivery systems. “Carigent has designed its RNAi delivery systems for both direct delivery (injection into organs and topical applications) and IV delivery. Our system can protect the RNAi until it gets where it needs to go, and we also can design our particles for sustained RNAi release. This can’t be done with lipids.” Dr. Feuerstein believes that multiple delivery vehicles will be required for various oligos and their specific applications. “We can’t solve every delivery problem with our technology, but we can deliver a lot of oligos to a lot of relevant targets.”

  • Ophthalmic Therapeutic Peptides

    Potentia Pharmaceuticals develops therapeutics to treat age-related macular degeneration (AMD) and other inflammatory ocular diseases. Potentia cofounder and COO Pascal Deschatelets, Ph.D., described the company’s approach to optical delivery of its drug candidate POT-4 for AMD treatment. 

    Lack of delivery options for ocular therapeutics continues to complicate the development of new drugs for severe eye disease, according to Dr. Deschatelets. Most drugs targeted to the back of the eye require frequent intravitreal injections, an uncomfortable procedure for patients that is associated with potential serious complications. The need for frequent intravitreal injection poses particular concern since many AMD patients may require life-long treatment.

    Rather than targeting angiogenesis as Genentech’s Lucentis does, POT-4 blocks activation of the complement system. POT-4, a synthetic 13-mer cyclic peptide, is structurally based on compstatin, a small molecule discovered at the University of Pennylvania.

    POT-4 works by binding to and inactivating the enzyme that cleaves C3, a key protein component of the complement cascade, into its active form. While a normally protective biochemical cascade that occurs in response to the presence of bacteria or other foreign substances, inappropriate or untimely complement activation can trigger organ transplant rejection reactions and other disorders that may include macular degeneration. 

    Over the past several years, genetic studies have identified polymorphisms in complement related genes that are associated with increased risk of AMD. Dr. Deschatelets explained that while “nobody really knows what causes AMD, genomic analysis has hinted that the complement pathway proteins are linked to all stages of macular degeneration and may constitute reasonable therapeutic targets.

    “Given the identification of a variety of complement-related genes encoding multiple proteins that promote local inflammation, tissue damage, and upregulation of angiogenic factors such as vascular endothelial growth factor in the eye, we believe that POT-4 holds the potential to be effective against both dry and wet AMD.”


Add a comment

  • You must be signed in to perform this action.
    Click here to Login or Register for free.
    You will be taken back to your selected item after Login/Registration.

Related content

Jobs

GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.
 Searching...
More »

GEN Poll

More » Poll Results »

Stopping Research Fraud

What is the best approach to curbing scientific misconduct and outright fraud?