Skin Heal – a particle-based formulation for improved wound healing

The effective and cost-efficient treatment of chronic wounds is a great challenge in healthcare. Demographic changes have resulted in a constant increase in chronic wounds – above all, diabetic ulcers. Previously, the amputation of extremities and the associated loss in quality of life have often been unavoidable. The development and evaluation of new forms of treatment for chronic skin disorders are therefore extremely important in regard to reducing costs and improving care. For the individual treatment of these chronic wounds we are developing particle-based formulations within the Fraunhofer “Beyond Tomorrow” project “SKIN HEAL”. The particles loaded with active agents can be integrated into commercial wound dressings or directly applied during treatment as pharmaceutical formulations.

Various particle technologies were used at the Fraunhofer IGB to formulate micro- and nanoparticles loaded with active agents. We use small molecules or proteins as active pharmaceutical ingredients (APIs). Chitosan, as well as its derivative chitosan hydrochloride, was chosen as the base material for the particles. Chitosan is a biobased, biocompatible polymer obtained from crustacean shells, which has antimicrobial properties. We have been able to successfully develop spray-drying procedures for the formulation of active agents that are implemented in wound healing, such as e.g., dexpanthenol or TGF-β (transforming growth factor). The Fraunhofer IGB has the Büchi Mini Spray Dryer B-290 and the Nano Spray Dryer B-90 available for this. The process parameters for spray drying using the Mini Spray Dryer were verified by design of experiments (DoE). This assures simple upscaling of the process parameters for the transmission of the spray drying process to the large-scale production process.

Dexpanthenol and TGF-β-loaded chitosan and chitosan hydrochloride particles can be produced using both the Mini and Nano Spray Dryer (Figs. 1 and 2). Design of experiments is, among other things, suitable for the optimization of the process parameters with regard to particle size. This process helped us to create a model that enables the targeted setting of the particle size (d₅₀) during particle production in the Mini Spray Dryer. This allowed us to produce chitosan particles with defined particle sizes of 2 µm, 5 µm and 10 µm. The particles were integrated into fibers of the CE certified silica fiber wound dressing (Fig. 4) at the Fraunhofer ISC. Chitosan particles with a diameter smaller than 5 µm were most suitable for this.

For the controlled release of the active agents, the chitosan and chitosan hydrochloride particles were crosslinked using ionic gelation with tripolyphosphate (TPP), and subsequent spray drying. The concentration of tripolyphosphate was varied and proportions of 0, 4, 7, 10 and 12 percent crosslinker were employed. The release rate of the active agent can effectively be controlled by the additional crosslinking of the matrix and the chosen level of crosslinking.

Spray drying is suitable as a process for the production of particle-based formulations for improved wound healing. The particles were successfully integrated into the wound dressing. The release properties of the active agents and particles can further be optimized by the variation of the capsule material or the additional coating of the particles. Various crosslinkers (covalent and non-covalent) in the production of the chitosan particles are currently being tested for this.

The particle systems developed here could be transferred to the most varying problems in the area of formulation, as well as small molecule agents and biopharmaceuticals. This has already enabled interferon to be encapsulated while retaining full bioactivity [1].

[1] Gruber-Traub, C.; Burger-Kentischer, A.; Gretzinger, S.; Hirth, T.; Weber, A. (2012) Spray drying of BSA- and interferon-β loaded chitosan particles. Chemie Ingenieur Technik 84, 343-348

We would like to thank the Fraunhofer-Gesellschaft for funding the project “SKIN HEAL”, within the ”Markets Beyond Tomorrow” program.

Fraunhofer ISC, Würzburg