A novel nano drug delivery system based on tigecycline-loaded calciumphosphate coated with poly-dl-lactide-co-glycolide |
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Authors: | Nenad L Ignjatovi? Petar Ninkov Roya Sabetrasekh and Dragan P Uskokovi? |
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Affiliation: | (1) Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Belgrade, Serbia;(2) Faculty of Dentistry, Department of Biomaterials, University of Oslo, Oslo, Norway; |
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Abstract: | The purpose of the study presented in this paper has been to examine the possibility of the synthesis of a new nanoparticulate
system for controlled and systemic drug delivery with double effect. In the first step, a drug is released from bioresorbable
polymer; in the second stage, after resorption of the polymer, non-bioresorbable calcium phosphate remains the chief part
of the particle and takes the role of a filler, filling a bone defect. The obtained tigecycline-loaded calcium-phosphate(CP)/poly(dl-lactide-co-glycolide)(PLGA) nanoparticles contain calcium phosphate coated with bioresorbable polymer. The composite was
analyzed by FT-IR, XRD and AFM methods. The average particle size of the nanocomposite ranges between 65 and 95 nm. Release
profiles of tigecycline were obtained by UV–VIS spectroscopy in physiological solution at 37°C. Experimental results were
analyzed using Peppas and Weibull mathematical models. Based on kinetic parameters, tigecycline release was defined as non-Fickian
transport. The cytotoxicity of the nanocomposite was examined on standard cell lines of MC3T3-E1, in vitro. The obtained low
values of lactate dehydrogenase (LDH) activity (under 37%) indicate low cytotoxicity level. The behaviour of the composite
under real-life conditions was analyzed through implantation of the nanocomposite into living organisms, in vivo. The system
with the lowest tigecycline content proved to be an adequate system for local and controlled release. Having in mind the registered
antibiotics concentration in other tissues, delivery systems with a higher tigecycline content show both local and systemic
effects. |
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