Abstract
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.
Highlights
The local functionalization of bone substitute materials (BSM) by adhesive drug delivery systems (DDS) is highly relevant for fracture healing and tissue regeneration within systemically altered bone, since osteotherapeutic drugs like bisphosphonates and bone surgery relevant antibiotics have undesired side effects like osteonecrosis or bacterial resistance, respectively, Nanomaterials 2016, 6, 53; doi:10.3390/nano6030053 www.mdpi.com/journal/nanomaterialsNanomaterials 2016, 6, 53 when given systemically
attenuated totalwell reflection (ATR)-FTIR Spectroscopy intensity spectra IR were recorded from the uncoated germanium internal reflection element (Ge IRE)
Human mesenchymal stem cells of four bone healthy donors were cultured from reaming debris that was collected during routine trauma surgery to stabilize fractures with osteosynthetic
Summary
The local functionalization of bone substitute materials (BSM) by adhesive drug delivery systems (DDS) is highly relevant for fracture healing and tissue regeneration within systemically altered bone (osteoporosis, multiple myeloma), since osteotherapeutic drugs like bisphosphonates and bone surgery relevant antibiotics have undesired side effects like osteonecrosis or bacterial resistance, respectively, Nanomaterials 2016, 6, 53; doi:10.3390/nano6030053 www.mdpi.com/journal/nanomaterials. Hybrid liposomes [3,4], polymeric micelles [5,6,7,8] or hollow polymer capsules [9,10,11,12], which have beneficial properties in the volume phase with respect to defined loading, releasing and cell targeting These nanoparticular polymer based DDS were not primarily used as adhesive coatings to our knowledge. General benefits of PEC are easy preparation in aqueous media under mild conditions, the absence of toxic solvents and the possibility to use biorelated compounds like polysaccharides and polypeptides From those adhesive PEC coatings two model drugs, rifampicin (RIF) and risedronate (RIS), are aimed to be released in a defined and delayed manner. The modification of Ti40Nb alloys, which is a mechanically favorable material for osteosynthetic plates, with drug loaded PEC coatings will be introduced and first results on drug release and biocompatibility given
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