Enabling Site-Specific Drug Delivery

PolyActiva has developed a platform technology that enables slow release, site-specific drug delivery directly at the site of action.  Upon application of the treatment, the drug is initiated immediately, and a constant daily dose delivers continuously for the intended treatment period.  Exceptional zero-order release profiles are achieved over treatment periods ranging from 1 to 12 months and there is no ‘burst’ effect on the first day of treatment.  All of our products are designed to biodegrade after the treatment period and leaving no residue.  As a consequence, PolyActiva’s delivery technology is very well suited to delivery at site of the body that have limited volumes, such as the anterior and posterior chambers of the eye, or the synovial cavity of joints.  This technology can be used to produce new biomedical products, drug-delivery devices and device components that enable delivery of drugs directly to the affected organ or treatment site. They are produced from a proprietary polymeric prodrug technology that represents a significant advance on current drug-polymer conjugate technology.  PolyActiva’s process involves the covalent attachment of the drug to a monomer unit via a selectively labile linker. The drug-monomer is then polymerised with suitable co-monomers or polymer segments to give a final polymeric prodrug, which may then be processed into a finished product with the desired geometry and physical characteristics.

The PolyActiva technology represents the next generation in drug delivery.

Key attributes include:

  • High Dose Loadings
    Higher drug loadings per mass of polymer than possible with conventional blend technologies.  More than 50% (w/w) of final polymer material is the target drug.  Allows sufficient drug to be carried in products of very small size, and still deliver therapeutic daily doses to the target site over extended periods.
  • Controlled and Selective Drug Release
    Exceptional zero-order release profiles ensure constant daily doses are delivered over the intended treatment period.
  • More Efficient Drug Release
    Drug is released in its active form and release process not involves intermediates to ensure drug can exert its therapeutic effect before being cleared from the site.
  • Biodegradable
    After treatment period, residual polymer biodegrades, biodegradation with safe and non-toxic by-products (e.g. glycerol, amino acids) leave no residue.
  • Modular
    Modular nature enables physicochemical properties to be tuned to meet requirements.
  • Multiple Drugs
    Suitable for products with multiple drugs.
  • Device Forming Capability
    The final material can then be processed into many forms such as rods / fibers / gels / coatings.

Overview : Polymeric Prodrug

The PolyActiva technology can be applied to any pharmaceutical application requiring site-specific drug delivery.  The applications ranging from development of ocular implants for the delivery of drugs to specific chambers of the eye (e.g. anterior or posterior chamber) to release of drug locally, to the synovial cavity of a loading bearing joint (e.g. knee).  In the case of the ocular implant, the product retains its physical rod-shape during the course of the treatment period and then biodegrades.  In the case of the intra-articular product, the product is retained in the synovial cavity as a high molecular weight gel, and controlled drug release is achieved despite the soluble nature of the polymer as the rate of drug release is controlled by the covalent attachment of the drug to the polymer rather than any diffusivity barrier.

The polymers produced using the PolyActiva technology are condensation or addition polymers (e.g. polyesters, polyurethanes, and triazoles).  Most polymer systems used by PolyActiva have a history of use in human therapeutic applications. The final material has a known polymer composition with a high level of drug substitution and control over both the position of the drug conjugation within the polymer and the polymer architecture.  Judicious selection of the monomer components can ensure that the by-products from biodegradation of the polymer are safe and non-toxic, often being either GRAS approved or endogenous substances. For example, use of monomers drug-monoglycerate (as the polyol) and ethyl ester of lysine diisocyanate (ELDI) will result in a polymeric prodrug that generates the by-products, glycerol, lysine, carbon dioxide, and ethanol on polymer biodegradation.  Typically, the drug is attached to the polymer backbone via a labile ester link. Breakdown of the ester bond will release the drug from the polymer backbone prior to the breakdown of the polymer.  The rate of drug release is separately controlled by independent chemistry incorporated into the polymer chain.

PolyActiva has developed two main platform systems for production of its polymer prodrugs.  One involves the use of polyurethanes esters, where the nature and proportion of the ester in the polymer chain can be used to control the rate of polymer biodegradation. PolyActiva has developed a library of bespoke co-monomer components that introduce biodegradation points and controlled points along the polymer backbone.  Polymeric prodrug are formed by reacting the drug-incorporating monomer with an appropriate co-monomer to form the final drug-polymer conjugate. Various polymeric prodrugs have been produced by PolyActiva, with drugs from a number of drug classes, including PG-analogues, β-blockers, fluoroquinolones, and non-steroidal anti-inflammatory drugs (NSAIDs).  PolyActiva has developed a library of bespoke monomer components that introduce biodegradation at controlled points along the polymer backbone.  The second system involves the use of polytriazole hydrogels with biodegradation chemistry incorporated into the hydrogel.  The polytriazole system allows polymeric prodrugs to be formed with drugs that have multiple reactive nucleophilic groups and have a high-risk of in-chain incorporation.  PolyActiva is able to produce polymers with defined architecture for both systems, including liner thermoplastic, cross-linked hydrogels and branched polymer systems.