In vitro evaluation of a multifunctional nano drug delivery system based on tigecycline-loaded calcium-phosphate/ poly-DL-lactide-co-glycolide

Abstract

Most drug delivery systems as treatment modalities for osteomyelitis have not been evaluated for resistant infections. Tigecycline (TG) is an antimicrobial agent that could be used in the treatment of multi-drug-resistant orthopedic infections. The objective of this in vitro study has been to determine what dosage of TG causes changes in the morphology and number of osteoblasts. We have also investigated whether nanoparticulate tigecycline-loaded calcium-phosphate/poly-DL-lactide-coglycolide is biocompatible and whether it could release bioactive TG in a controlled manner during the observation time. The cytotoxicity was tested by analyzing the release of lactate dehydrogenase from dead osteoblasts to the medium. Staphylococcus aureus was used to verify the antibacterial effect of the multifunctional drug delivery system. At concentrations as achieved by local application, TG caused high toxic effect and impaired the normal osteoblastic morphology. The nanoparticulate multifunctional drug delivery system showed good compatibility and antibacterial effect during the observation time and thus appears to be suitable for the treatment of osteomyelitis caused by multi-drug-resistant microbes.

Molecular designing of nanoparticles and functional materials

“…[30][31][32][33] The novel concept involving a simultaneous, controlled release of a drug and a prodrug with different physicochemical properties was applied in order to prolong the release period of antibiotics and estimate their high local concentrations, which are the necessary preconditions for the treatment of some chronic infectious diseases. [30][31][32][33][34] Multifunctional nano-particulate HAp-based powders were prepared for the purpose of: a) either fast or sustained, local delivery of cholecalciferol (D 3 ) and b) the secondary, osteoconductive and defect-filling effect of the carrier itself. 35 Synthesized nanoparticles (average particle size, d 50 = 71 nm) of HAp-coated with D 3 loaded PLGA had the zeta potential of -33.4 mV, characteristic for the stable and aggregation-resistant particles.…”