An interfacial local drug delivery system (DDS) concept for therapeutic proteins related to bone healing based on coatings of polyelectrolyte complex (PEC) nanoparticles (NP) is described. This concept is an extension of similar DDS for low molecular drugs [1, 2, 3, 4] and can be used for the functionalization of bone substituting materials (BSM) related to the therapy of systemic bone diseases. As protein therapeutics bone morphogenetic proteins (BMPs) and the brain derived neuronal factor (BDNF) were considered. PEC NP were obtained by mixing cationic and anionic polysaccharides and proteins at defined molar mixing ratio and pH value. Additionally, thermoresponsive copolyelectrolytes of poly(N-isopropylacrylamide) (PNIPAAM) were integrated to switch deliver properties. Importantly, low cost chymotrypsin (CHY) and papain (PAP) served as model proteins for high cost BMPs and BDNF due to similar isoelectric points and molecular weights. Dispersions of PEC/Protein NP were colloidally stable over weeks shown by dynamic light scattering (DLS) and kept adhesive at model substrates and BSM after contact to related buffers and cell media shown by IR spectroscopy. Sustained slower releases were found for BMPs  and BDNF for at least 14 days and smaller initial bursts compared to model proteins CHY and PAP. Biological activity tests of released BMP-2 at mouse myoblasts indicated SMAD 1/5 formation, which is a specific signaling protein involved in differentiation to osteoblasts .
Conclusively, therapeutic protein loaded PEC NPs are promising DDS and will be applied at BSM like osteosynthetic plates and bone cements in the future.
This work is related to the Sonderforschungsbereich Transregio 79 (TRR 79, projects M7, M9, B7, T2) “Materials for tissue regeneration within systemically altered bones” supported by DFG involving universities and research institutes in Gießen, Heidelberg and Dresden, Germany.
1. Biomed. Anal. 2012, 66, 183-190 2. Biointerphases 2013, 8:25 3. Biointerphases 2015, 10(1) 011001-011010 4. Nanomaterials 2016, 6(3), 53. 5. Coll. Surf. B. Biointerfaces (submitted)