An overview is given on 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. Drug loaded PEC NP have certain advantages in this application field, which are exemplarily summarized herein.
Preparatively, PEC NP were fabricated by defined mixing biorelated polycation and polyanion solutions and integration of charged drugs during or after mixing. Importantly, a stoichiometric ratio related to cationic and anionic units of polymer and drug close to zero was considered. Analytically, a broad range of physical-chemical methods 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 and standard biochemical and microbiological assays were applied to characterize colloid stability, adhesiveness, drug loading and release as well as cell interaction and viability.
As results various drug/PEC NP systems show time dependent colloidal stability for weeks up to months enabling storage, transport and application in the medical field. Secondly, deposited and dried drug/PEC NP feature a local wet adhesive PEC matrix at model systems and applied BSM in contact to relevant aqueous media (e.g. buffer, cell culture medium, body fluids) minimizing systemic toxicity. Thirdly, PEC NP coating systems are identified showing minimal effects on various relevant bone related cells due to biorelateness, low excess charge, local confinement and low surface area. Fourthly, PEC NP release bone healing drugs like bisphosphonates, antibiotics and bone morphogenetic proteins with defined kinetics. Especially, the onset of drug release could be switched by thermoresponsive poly(N-isopropylacrylamide) containing PEC NP systems within physiological temperature range allowing spatiotemporal drug release on demand.
US 9,078,805 B2 (2015), EP 2 552 405 B1 (2017)
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