Calcium phosphate cements as bone drug delivery systems: A review

Ginebra, Maria‐Pau; Traykova, T.; Planell, Josep A.

doi:10.1016/j.jconrel.2006.04.007

Cited by 613 publications

(448 citation statements)

References 59 publications

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“…Low-dose antimicrobial-loaded bone cement releases only a very small fraction of the drug load during the first week when it is needed [42,52,62]. Other investigational delivery vehicles, including calcium phosphate cements [30], hydroxyapatite composites [9,61], antibiotic implant coatings [2,3], and polymer beads/microparticles [4,46,47], also have drawbacks. Prolonged or incomplete degradation of some resorbable delivery vehicles such as poly(lactic-co-glycolic acid) and polyanhydrides has limited their use [34,46].…”

Section: Introductionmentioning

confidence: 99%

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Overstreet

McLaren

Calara

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Local delivery can achieve the high antimicrobial concentrations necessary to kill biofilm-related microbes. Degradation times for resorbable carriers are too long. Hydrogels (gels of hydrophilic polymer in water) can degrade faster but release antimicrobials too quickly. We previously developed hydrogels based on the copolymer poly(N-isopropylacrylamide-co-dimethyl-c-butyrolactone acrylate-co-Jeffamine 1 M-1000 acrylamide) (PNDJ) with delivery times of several days with complete degradation in less than 6 weeks. Questions/purposes We asked: (1) What is the elution profile of gentamicin from PNDJ hydrogels? (2) Is gentamicin released from gentamicin-loaded PNDJ (G-PNDJ) hydrogel effective for treatment of orthopaedic infection? (3) Does local gentamicin delivery from G-PNDJ hydrogel cause renal dysfunction? Methods (1) Two formulations of G-PNDJ, lower dose (1.61 wt%) and higher dose (3.14 wt%), five samples each, were eluted in buffered saline under infinite sink conditions. (2) Infections were induced in 16 New Zealand White rabbits by inserting a Kirschner wire in a devascularized radius segment and inoculating with 7.5 9 10 6 colony-forming units Staphylococcus aureus. At 3 weeks, débridement was performed and a new Kirschner wire was placed in the dead space. Treatment was randomized to higher-dose G-PNDJ or no hydrogel. No systemic antimicrobials were used. Positive culture and acute inflammation on histology were used to determine the presence of infection 4 weeks postdébridement. (3) 3.14 wt% G-PNDJ, 0.75, 1.5, or 3.0 mL, was injected subcutaneously in nine Sprague-Dawley rats, three of each dose. Serum gentamicin, blood urea nitrogen, and creatinine were measured on Days 1, 3, 7, 14, and 28. Results (1) Gentamicin release was sustained over 7 days with the higher-dose formulation release profile similar to release from high-dose antimicrobial-loaded bone cement.(2) Four weeks postdébridement, infection was present in eight of eight no-hydrogel rabbits but zero of eight rabbits treated with G-PNDJ hydrogel (p \ 0.001). (3) Blood urea nitrogen and creatinine were transiently elevated

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Section: Introductionmentioning

confidence: 99%

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Overstreet

McLaren

Calara

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…There are 11 known CPCs with various calcium-to-phosphate (Ca/P) molar ratios in the ternary system Ca(OH) 2 -H 3 PO 4 -H 2 O (Table 1). Research and development of materials comprised of CPCs are currently in progress, especially in the fields of medicine and dentistry (e.g., see Martin and Brown, 1995;Bohner et al, 2006;Ginebra et al, 2006). Medical CPC paste, however, is extremely expensive and has high viscosity, which makes it unfeasible for engineering applications.…”

Section: Introductionmentioning

confidence: 99%

Novel grout material comprised of calcium phosphate compounds: In vitro evaluation of crystal precipitation and strength reinforcement

Akiyama¹,

Kawasaki

2012

Engineering Geology

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Calcium phosphate compounds (CPCs) have unique physicochemical properties. As grout material, they afford many advantages such as adequate physical strength, self-setting property, pH dependence of precipitation, non-toxicity, and recyclability. To apply CPCs to the permeability control and reinforcement of ground soil and rock, we explored suitable conditions for in vitro CPC precipitation, conducted unconfined compressive strength (UCS) tests of Toyoura sand test pieces cemented by CPC, and carried out observations and elemental analysis of precipitated CPC crystals.Two kinds of phosphate stock solution and two kinds of calcium stock solution were used to prepare the reaction mixtures, and CPC precipitation was detected in all reaction mixtures. The volume of CPC precipitation in the reaction mixture increased as the pH rose from strongly acidic to around neutral. The UCS of Toyoura sand test pieces cemented by 1.5 M diammonium phosphate and 0.75 M calcium acetate tended to increase with time, reaching a maximum of 63.5 kPa after 14 days of curing. Conversely, the UCS of test pieces cemented by using calcium nitrate was below 20 kPa and showed no significant increase in strength. CPC precipitation with calcium nitrate induced the formation of plate-like crystals, whereas that with calcium acetate induced whisker-like crystals.Elemental analysis of the cemented test pieces showed that the distributions of phosphorus and calcium were similar. The results indicate the practical feasibility of using novel CPC grouts as chemical grouts because of their self-setting property, and as biogrouts because of their crystal 3 structure and pH dependence of precipitation.

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“…The absorbing properties of HAP have been exploited in the formation of HAP-antibiotic and HAP-drug composites for slow release in situ [14][15][16]. This has proved effective in the treatment of diseases such as osteomyelitis as it allows better recovery from the disease [17].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterisation of nanohydroxyapatite using an ultrasound assisted method

Poinern

Brundavanam

Mondinos

et al. 2009

Ultrasonics Sonochemistry

152

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Nanostructured hydroxyapatite (HAP) was prepared by a wet precipitation method using Ca(NO 3 ) and KH 2 PO 4 as the main material and NH 3 as the precipitator under ultrasonic irradiation. The Ca/P ratio was set at 1.67 and the pH maintained at a minimum of 9. The temperature conditions and ultrasound influences were investigated using X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM) and Fourier Transform Infrared Spectroscopy (FT-IR). The results showed that Nano-HAP can be obtained by this method and the particles were achieved to around 30nm.

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Calcium phosphate cements as bone drug delivery systems: A review

Cited by 613 publications

References 59 publications

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Novel grout material comprised of calcium phosphate compounds: In vitro evaluation of crystal precipitation and strength reinforcement

Synthesis and characterisation of nanohydroxyapatite using an ultrasound assisted method

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