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The first part of this review looks at the fundamental properties of hydroxyapatite (HAP), the basic mineral constituent of mammalian hard tissues, including the physicochemical features that govern its formation by precipitation. A special emphasis is placed on the analysis of qualities of different methods of synthesis and of the phase transformations intrinsic to the formation of HAP following precipitation from aqueous solutions. This serves as an introduction to the second part and the main subject of this review, which relates to the discourse regarding the prospects of fabrication of ultrafine, nanosized particles based on calcium phosphate carriers with various therapeutic and/or diagnostic agents coated on and/or encapsulated within the particles. It is said that the particles could be either surface-functionalized with amphiphiles, peptides, proteins, or nucleic acids or injected with therapeutic agents, magnetic ions, or fluorescent molecules. Depending on the additive, they could be subsequently used for a variety of applications, including the controlled delivery and release of therapeutic agents (extracellularly or intracellularly), magnetic resonance imaging and hyperthermia therapy, cell separation, blood detoxification, peptide or oligonucleotide chromatography and ultrasensitive detection of biomolecules, and in vivo and in vitro gene transfection. Calcium phosphate nanoparticles as carriers of therapeutic agents that would enable a controlled drug release to treat a given bone infection and at the same be resorbed in the body so as to regenerate hard tissue lost to disease are emphasized hereby as one of the potentially attractive smart materials for the modern medicine., (© 2010 Wiley Periodicals, Inc.)

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.

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-co-glycolide 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. [ABSTRACT FROM AUTHOR]

Abstract: Development of a material for simultaneous sustained and localized delivery of antibiotics and induction of spontaneous regeneration of hard tissues affected by osteomyelitis stands for an important clinical need. In this work, a comparative analysis of the bacterial and osteoblastic cell response to two different nanoparticulate carriers of clindamycin, an antibiotic commonly prescribed in the treatment of bone infection, one composed of calcium phosphate and the other comprising poly-(D,L-lactide-co-glycolide)-coated calcium phosphate, was carried out. Three different non-cytotoxic phases of calcium phosphate, exhibiting dissolution and drug release profiles in the range of one week to two months to one year, respectively, were included in the analysis: monetite, amorphous calcium phosphate and hydroxyapatite. Spherical morphologies and narrow size distribution of both types of nanopowders were confirmed in transmission and scanning electron microscopic analyses. The antibiotic-containing powders exhibited sustained drug release contingent upon the degradation rate of the carrier. Assessment of the antibacterial performance of the antibiotic-encapsulated powders against Staphylococcus aureus, the most common pathogen isolated from infected bone, yielded satisfactory results both in broths and on blood agar plates for all the analyzed powders. In contrast, no cytotoxic behavior was detected upon the incubation of the antibiotic powders with the osteoblastic MC3T3-E1 cell line for up to three weeks. The cells were shown to engage in a close contact with the antibiotic-containing particles, irrespective of their internal or surface phase composition, polymeric or mineral. At the same time, both types of particles upregulated the expression of osteogenic markers osteocalcin, osteopontin, Runx2 and protocollagen type I, suggesting their ability to promote osteogenesis and enhance remineralization of the infected site in addition to eliminating the bacterial source of infection. [Copyright &y& Elsevier]