Polyelectrolyte Complex Based Interfacial Drug Delivery System with Controlled Loading and Improved Release Performance for Bone Therapeutics.
An improved interfacial drug delivery system (DDS) based on polyelectrolyte complex (PEC) coatings with controlled drug loading and improved release performance was elaborated. The cationic homopolypeptide poly(l-lysine) (PLL) was complexed with a mixture of two cellulose sulfates (CS) of low and high degree of substitution, so that the CS and PLL solution have around equal molar charged units. As drugs the antibiotic rifampicin (RIF) and the bisphosphonate risedronate (RIS) were integrated. As an important advantage over previous PEC systems this one can be centrifuged, the supernatant discarded, the dense pellet phase (coacervate) separated, and again redispersed in fresh water phase. This behavior has three benefits: (i) Access to the loading capacity of the drug, since the concentration of the free drug can be measured by spectroscopy; (ii) lower initial burst and higher residual amount of drug due to removal of unbound drug and (iii) complete adhesive stability due to the removal of polyelectrolytes (PEL) excess component. It was found that the pH value and ionic strength strongly affected drug content and release of RIS and RIF. At the clinically relevant implant material (Ti40Nb) similar PEC adhesive and drug release properties compared to the model substrate were found. Unloaded PEC coatings at Ti40Nb showed a similar number and morphology of above cultivated human mesenchymal stem cells (hMSC) compared to uncoated Ti40Nb and resulted in considerable production of bone mineral. RIS loaded PEC coatings showed similar effects after 24 h but resulted in reduced number and unhealthy appearance of hMSC after 48 h due to cell toxicity of RIS.
Department of Polyelectrolytes and Dispersions, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, Dresden D-01069, Germany. vehlow@ipfdd.de.|Department of Chemistry and Food Chemistry, Technical University Dresden, Mommsenstrasse 4, Dresden D-01062, Germany. vehlow@ipfdd.de.
David
D
Vehlow
Department Chemistry of Functional Materials, Leibniz-Institute for Solid State and Materials Research Dresden, Helmholtzstrasse 20, Dresden D-01069, Germany. r.schmidt@ifw-dresden.de.
Romy
R
Schmidt
Department Chemistry of Functional Materials, Leibniz-Institute for Solid State and Materials Research Dresden, Helmholtzstrasse 20, Dresden D-01069, Germany. a.gebert@ifw-dresden.de.
Annett
A
Gebert
Institute of Experimental Trauma Surgery, Justus-Liebig-University, Schubertstrasse 81, Giessen 35392, Germany. maximilian.siebert@med.uni-giessen.de.
Maximilian
M
Siebert
Institute of Experimental Trauma Surgery, Justus-Liebig-University, Schubertstrasse 81, Giessen 35392, Germany. katrin.s.lips@chiru.med.uni-giessen.de.
Katrin Susanne
KS
Lips
Department of Polyelectrolytes and Dispersions, Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, Dresden D-01069, Germany. mamuller@ipfdd.de.|Department of Chemistry and Food Chemistry, Technical University Dresden, Mommsenstrasse 4, Dresden D-01062, Germany. mamuller@ipfdd.de.
Martin
M
Müller
attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR); biocompatibility; drug delivery; hMSC; polyelectrolyte complex; rifampicine; risedronate