Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement

Mestres, Gemma; Kugiejko, Karol; Pastorino, David; Unosson, Johanna; Öhman, Caroline; Ott, Marjam Karlsson; Ginebra, Maria‐Pau; Persson, Cecilia

doi:10.1016/j.msec.2015.08.016

Cited by 11 publications

(10 citation statements)

References 56 publications

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“…Which is consistent with the typical drug release profile from CPC (Ginebra et al, 2012). Also, the same trend has been observed in the release profile of CPC cement loaded with various drugs such as simvastatin (Mestres et al, 2016) and vancomycin (Cabrejos-Azama et al, 2016) which inhibit bacterial activity within the first days. This significant initial increase in the released drug level was related to the part of drug physically entrapped by the cement.…”

Section: Drug Releasesupporting

confidence: 84%

Fabrication of alginate modified brushite cement impregnated with antibiotic: Mechanical, thermal, and biological characterizations

Dabiri

Lagazzo

Aliakbarian

et al. 2019

J Biomedical Materials Res

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Treatment of postsurgical infections, associated with orthopedic surgeries, has been a major concern for orthopedics. Several strategies including systematic and local administration of antibiotics have been proposed to this regard. The present work focused on fabricating alginate (Alg) modified brushite (Bru) cements, which could address osteogeneration and local antibiotic demands. To find the proper method of drug incorporation, Gentamicin sulfate (Gen) was loaded into the samples in the form of solution or powder. Several characterization tests including compression test, morphology, cytotoxicity, and cell adhesion assays were carried out to determine the proper concentration of Alg as a modifier of the Bru cement. The results indicated that addition of 1 wt% Alg led to superior mechanical and biological properties of the cement. Moreover, Alg addition changed the morphology of the cement from plate and needle‐like structures to petal‐like structure. Fourier transform infrared spectroscopy results confirmed the successful loading of Gen on the cements, specifically when Gen solution was used, and X‐Ray Diffractometer result indicated that Gen caused a decrease in crystalline size. Furthermore, thermal analysis revealed that Gen‐loaded sample had more stable structure as the transformation temperature slightly shifted to a higher one. The stability study confirmed the chemical stability and adequate mechanical performance of the cements within 1 month of soaking time. Finally, the addition of Alg has a positive impact on the release behavior at low concentration of Gen solution so that 20% decrease within 2 weeks of release experiment was remarkably detected.

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Section: Drug Releasesupporting

confidence: 84%

Fabrication of alginate modified brushite cement impregnated with antibiotic: Mechanical, thermal, and biological characterizations

Dabiri

Lagazzo

Aliakbarian

et al. 2019

J Biomedical Materials Res

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“…The skeletal density, total porosity, and specific surface area were in accordance with previous results and displayed no significant differences among control i-CPF and PITA loaded i-CPF at 100 μM. These findings were in agreement with other studies for statins, where they showed that SIM did not alter phase composition or porosity of cements (Mestres et al, 2016).…”

Section: Discussionsupporting

confidence: 92%

“…The initial burst release recorded was in agreement with other findings showing freshly prepared CPCs or pre‐set CPCs set for short times, which also display burst release (Mestres et al, ). The Korsmeyer‐Peppas model was fitted to analyze the release kinetics (Table ) but did not allow any conclusion as the parameter ( n ) was too low for the case of release from flat surfaces.…”

Section: Discussionsupporting

confidence: 91%

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Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent

et al. 2019

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Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i‐CPF) based on α‐tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i‐CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i‐CPFs, which retained their biomimetic features. PITA‐loaded i‐CPFs showed a dose‐dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose‐dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i‐CPFs loaded with PITA as osteogenic and angiogenic agent.

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“…The use of the cement at different setting times can allow for modelling the release behaviour of clinically applicable injectable cements at different stages of setting and hardening. Therefore, in the follow-up work from 2015, Mestres et al [ 37 ] focused their attention on a brushite cement matrix prepared at different times: 3 min (fresh cement) and 1 h and 15 h as pre-set cements. Simvastatin was selected as the model drug and loaded onto the abovementioned cements.…”

Section: General Matrix Featuresmentioning

confidence: 99%

Factors influencing the drug release from calcium phosphate cements

Fosca

Rau

Uskoković³

2022

Bioactive Materials

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Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.

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Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement

Cited by 11 publications

References 56 publications

Fabrication of alginate modified brushite cement impregnated with antibiotic: Mechanical, thermal, and biological characterizations

Fabrication of alginate modified brushite cement impregnated with antibiotic: Mechanical, thermal, and biological characterizations

Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent

Factors influencing the drug release from calcium phosphate cements

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