Abstract
The bone therapeutic drug zoledronate (ZOL) was loaded at and released by polyelectrolyte complex (PEC) particle films composed of either pure poly(ethyleneimine) (PEI) or maltose-modified poly(ethyleneimine) (PEI-M) and oppositely charged cellulose sulfate attached to model germanium (Ge) substrates by solution casting. Dispersions of colloidally stable polyelectrolyte complex (PEC) particles in the size range 11-141 nm were obtained by mixing PEI or PEI-M, CS and ZOL in defined stoichiometric ratios. TRANS-FTIR spectroscopy was used to determine the stability of the PEC films against detachment, in-situ-ATR-FTIR spectroscopy for the ZOL loss in the PEC film and UV-VIS spectroscopy for the ZOL enrichment of the release medium. Films of casted ZOL/CS/PEI-M or ZOL/CS/PEI particles were stable in contact to water, while films of the pure drug (ZOL) and of the binary systems ZOL/PEI-M or ZOL/PEI were not stable against detachment. Retarded releases of ZOL from various PEC films compared to the pure drug film were observed. The molecular weight of PEI showed a considerable effect on the initial burst (IB) of ZOL. No significant effect of the maltose modification of PEI-25 K on IB could be found. Generally, after one day the ZOL release process was finished for all measured ZOL/PEC samples and residual amounts of 0-30% were obtained. Surface adhesive drug loaded PEC particles are promising drug delivery systems to supply and release a defined amount of bone therapeutics and to functionalize bone substitution materials.
Highlights
Functionalization of bone substitution materials (BSM) by local interfacial delivery systems for bone therapeutic drugs is a highly relevant strategy to improve bone healing after fractions associated with systemic bone diseases like osteoporosis or multiple myeloma [1]
Size of polyelectrolyte complex (PEC) particles Particle sizes of unloaded and ZOL loaded (ZOL/PEC-1:5) complexes of PEI-1.3 K/cellulose sulfate (CS), PEI-25 K/CS, PEI-750 K/CS and PEI-M-25 K-1:5/CS were determined by dynamic light scattering (DLS)
Both sizes and count rates for PEC-1.1 particles were in most cases smaller compared to PEC-0.9 particles
Summary
Functionalization of bone substitution materials (BSM) by local interfacial delivery systems for bone therapeutic drugs is a highly relevant strategy to improve bone healing after fractions associated with systemic bone diseases like osteoporosis or multiple myeloma [1]. In this report we address and point out colloidal properties, adhesiveness and retarded release of ZOL loaded PEC particle systems based on PEI or PEI-M and CS under variation of PEI molecular weight and the PEC particle net charge sign.
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