Aphios (www.aphios.com) is developing a series of biodegradable polymer microspheres (nanospheres) that encapsulate a range of drugs. It has developed a scalable, single process to produce biodegradable polymer nanospheres using fluids without organic solvents—its SuperFluids technology—to encapsulate proteins, says CEO Trevor Castor, Ph.D. Many other types of microspheres are produced in a five-step, costly process using organic solvents that denature proteins. Aphios are monodisperse polymers, and as such, can be used for the controlled release of viral vaccine antigens because they improve the stability of antigens in the body for long periods of time.
Aphios’ portfolio also includes phospholipid nanosomes for increased efficacious delivery and reduction of toxicity of hydrophobic drugs such as camptothecin (Camposomes), paclitaxel (Taxosomes), and bryostatin (Bryosomes).
Hydrophilic compounds, such as recombinant proteins, are encapsulated in the aqueous core, whereas hydrophobic compounds, such as anticancer drugs and water-insoluble drugs, are trapped within lipid bilayers.
Encapsulation masks the water-insoluble nature of drugs. The company’s protein nanoparticles can deliver insulin, proteins, nucleic acids, and a range of enzymes. Its carriers are being used for CNS, oncology, infectious diseases, and nutraceuticals.
Flamel Technologies (www.flamel.com) has two drug-delivery platforms for delivering new and extant drugs: the Medusa and Micropump® technologies. Medusa is a self-assembled poly-amino acid nanoparticle injectable system, which is geared to deliver first- and second-generation long-acting protein drugs. It uses naturally occurring hydrophilic and hydrophobic amino acids to form a stable polymer that forms stable nanoparticles spontaneously in water, not solvent. The amphiphilic character of the polymers drives the self-assembling of the nanoparticles in water.
These nonimmunogenic nanoparticles, which are 20–50 nanometers in diameter, are composed of 95% water and 5% polyamino acid polymer. They are robust over a wide range of pH values and can be stored as stable liquid or stable dry forms. The company says this formulation reduces the intensity of the peak administration, which is the cause of many side effects, and maintains the concentration of protein drugs for at least two weeks or more in dog models, offering a long duration of action with improved efficacy, as well as improving the solubility-viscosity of insoluble protein drugs such as IL-2. They are also inexpensive to produce.
Two second-generation products, Basulin (insulin) and IFN alpha-2b XL, are the most advanced (Phase II and Phase I, respectively), followed by IL-2XL (Phase I). Human growth hormone and IFN beta XL are in animal studies.
Flamel’s Micropump is designed for oral, controlled-release delivery of small molecule drugs, with special utility for pediatric and geriatric patients. Micropump I enables extended-release, and Micropump II enables delayed and extended-release (up to 24 hours) by enabling drugs to remain longer in the small intestine. This multiple-dose system contains 5,000 to 10,000 microparticles per capsule or tablet, which releases 200-500 micron-sized microparticles in the stomach and small intestine, where each microparticle releases the drug by osmotic pressure at an adjustable rate (controlled for Micropump I or delayed for Micropump II) and over an extended period of time.
Flamel has deals for its Micropump technology with GlaxoSmithKline(www.gsk.com) for Coreg-CR, a beta-blocker in Phase IV registration; with Servier(www.servier.com) for an ACE-inhibitor; and with Merck(www.merck.com) for an undisclosed drug. It is also developing Genvir (acyclovir), Metformin XL, and Augmentin SR.