Adhesive Drug Delivery Systems Based on Polyelectrolyte Complex Nanoparticles (PEC NP) for Bone Healing

Abstract

Background: In this contribution an overview is given on own work concerning drug loaded Polyelectrolyte Complex (PEC) Nanoparticles (NP) used to functionalize Bone Substitute Materials (BSM) for the therapy of bone defects associated with systemic bone diseases. In this context, drug loaded PEC NP have certain advantages, which are exemplarily summarized herein. Methods: Concerning preparative methods PEC NP were fabricated by controlled mixing of polycation and polyanion solutions and integration of charged drugs during and after mixing. Control was taken on the stoichiometric ratio related to cationic and anionic repeating units, which was chosen close to zero for the final applied PEC NP. Concerning analytical methods a couple of physical-chemical methods were applied like colloid titration, Dynamic Light Scattering (DLS), Scanning Force Microscopy (SFM), Fourier Transform infrared (FTIR) spectroscopy, Ultraviolet-Visible (UV-VIS) and Circular Dichroism (CD) spectroscopy to characterize colloid stability, adhesiveness, drug loading and release of PEC NP. Moreover, standard biochemical and microbiological assays were applied. Conclusion: Drug loaded PEC NP consist of oppositely charged biorelated Polyelectrolytes (PEL) like ionic polysaccharides or ionic polypeptides and also synthetic PEL, which are mixed and processed in aqueous media. At first, freshly prepared drug/PEC NP exhibit time dependent colloidal stability in the range of weeks and months, which enables and simplifies storage, transport and application in the medical field. Secondly, after deposition and drying of drug/PEC NP a local wet adhesive PEC matrix at the BSM remains in contact to relevant aqueous media (e.g. buffer, cell culture medium), which minimizes asepsis, systemic toxicity, immune or inflammatory reaction. Thirdly, cell compatible PEC NP coatings were identified, which showed only minimal effects on various relevant bone related cells due to biorelateness, complexation, local confinement and low surface area. Fourthly, PEC NP elute drugs for bone healing like bisphosphonates, antibiotics and growth factors (e.g. bone morphogenetic proteins) in delayed and sustained manner. Moreover, the onset of elution could be triggered by thermoresponsive PEL via temperature increase giving clinicians a tool into hand allowing spatiotemporal drug release on demand. Finally, drug/PEC NP could be integrated into commercial or still developed allotropic stabilizing or defect filling BSM systems.