A novel nano drug delivery system based on tigecycline-loaded calciumphosphate coated with poly-dl-lactide-co-glycolide

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 degrees 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.

Applications of nanparticle based drug delivery systems in bone tissue engineering

“…The average size was from 65-95 nm. This composited nanoparticles proved to be an adequate system for local and controlled drug release [50]. Another group of novel composite nanoparticles combining glycidyl methacrylate derivatised dextrans with gelatine was reported.…”

Multifunctional and hybrid systems based on calcium-phosphate and hydroxyapatite for preventive and regenerative medicine

“…Upravo ovakav koncept je primenjen u dizajniranju nHAP-a za lokalnu dostavu tigeciklina a u cilju lečenja osteomijelitisa [63,64]. Kompozitni biomaterijal na bazi HAp/PLLA [65], sa visoko kristalnom HAp fazom, je sintetizovan u dva koraka.…”

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

“…66 Apart from PLGA-related nanomaterials, other targeted delivery systems for bone diseases were reported. For example, Ignjatović et al 67 reported a double delivery system where a new nanoparticulate system for controlled and systemic drug delivery with double effect was reported. In their design, the drug is released from the bioresorbable polymer first; then, after resorption of the polymer, nonbioresorbable calcium phosphate remains the chief part of the particle and takes the role of a filler, filling a bone defect.…”