An interfacial local drug delivery system (DDS) concept for bone morphogenetic protein 2 (BMP-2) based on coatings of polyelectrolyte complex (PEC) nanoparticles (NP) is described in analogy to similar systems for low molecular drugs . Such DDS can be used for the functionalization of bone substituting materials (BSM) related to the therapy of systemic bone diseases. Nanoparticular ternary complexes of cationic and anionic polysaccharides and recombinant human BMP-2 were prepared in dependence of the molar mixing ratio, pH value and the cationic polysaccharide . Two further weakly basic proteins chymotrypsin (CHY) and papain (PAP) served as model proteins for BMP-2 due to similar isoelectric points and molecular weights. The cationic polysaccharides ethylenediamine modified cellulose (EDAC) or trimethylammonium modified cellulose (PQ10) were combined with the anionic polysaccharide cellulose sulphate (CS), respectively. Mixing EDAC or PQ10 and protein solutions according to a weakly either anionic or cationic excess charge colloidal ternary dispersions formed, which were cast onto germanium model substrates and dried. These dispersions were colloidally stable for at least one week, as shown by dynamic light scattering (DLS). Furthermore, Fourier Transform Infrared (FTIR) and circular dichroism (CD) spectroscopy showed that protein loaded PEC NP coatings remain bound at the model substrate after contact to HEPES buffer and exclusively CHY, PAP and BMP-2 are slowly released. Advantageously, BMP-2 showed the smallest initial burst and the slowest release kinetics in comparison to CHY and PAP. Only approximately 25% of the initial BMP-2 content was released within 14 days. Thus, BMP-2 loaded PEC NPs are promising for the functionalization of BSM. Future work on this approach will be dedicated to additional growth factors and in vitro biological experiments related to the therapy of systemic bone diseases.
References and Acknowledgements
This work is related to the Sonderforschungsbereich Transregio 79 (TRR 79, projects M7, M9, T2) entitled “Materials for tissue regeneration within systemically altered bones” supported by the Deutsche Forschungsgemeinschaft (DFG) involving universities and research institutes in Gießen, Heidelberg and Dresden, Germany.
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