Mechanism of formation governs the mechanism of release of antibiotics from calcium phosphate nanopowders and cements in a drug-dependent manner

Uskoković, Vuk

doi:10.1039/c9tb00444k

Cited by 28 publications

(16 citation statements)

References 45 publications

(42 reference statements)

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“…Bisso et al used a similar approach for the dual delivery of bisphosphates and nucleic acids [37]. Therapeutic factors can be loaded onto calcium phosphate particles either during the synthesis of the calcium phosphate through co-precipitation [38,39,40] or by combining with the calcium phosphate powders post-synthesis through absorption processes [36]. Co-precipitation can achieve strong chemical interactions between the therapeutic factor and calcium phosphate.…”

Section: Drug and Therapeutic Factor Deliverymentioning

confidence: 99%

“…The interactions that occur vary depending on the antibiotic used. For example, Uskoković successfully combined vancomycin and ciprofloxacin with both amorphous and crystalline HA nanoparticles and found that vancomycin was released more when amorphous powders were used, whereas ciprofloxacin was released more quickly when using the crystalline powders [40]. Gbureck et al demonstrated that vancomycin and ofloxacin created only weak bonds with calcium phosphate nanoparticles and reported that the absorption of these antibiotics was dependent on their specific surface area and not composition [49].…”

Section: Drug and Therapeutic Factor Deliverymentioning

confidence: 99%

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Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

2019

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Bone injuries and diseases constitute a burden both socially and economically, as the consequences of a lack of effective treatments affect both the patients’ quality of life and the costs on the health systems. This impended need has led the research community’s efforts to establish efficacious bone tissue engineering solutions. There has been a recent focus on the use of biomaterial-based nanoparticles for the delivery of therapeutic factors. Among the biomaterials being considered to date, calcium phosphates have emerged as one of the most promising materials for bone repair applications due to their osteoconductivity, osteoinductivity and their ability to be resorbed in the body. Calcium phosphate nanoparticles have received particular attention as non-viral vectors for gene therapy, as factors such as plasmid DNAs, microRNAs (miRNA) and silencing RNA (siRNAs) can be easily incorporated on their surface. Calcium phosphate nanoparticles loaded with therapeutic factors have also been delivered to the site of bone injury using scaffolds and hydrogels. This review provides an extensive overview of the current state-of-the-art relating to the design and synthesis of calcium phosphate nanoparticles as carriers for therapeutic factors, the mechanisms of therapeutic factors’ loading and release, and their application in bone tissue engineering.

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Section: Drug and Therapeutic Factor Deliverymentioning

confidence: 99%

Section: Drug and Therapeutic Factor Deliverymentioning

confidence: 99%

Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

2019

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“…The insulin proxy release profiles were also analyzed for the mechanism of release based on the fits with the Korsmeyer–Peppas kinetic model. For the release from MnO 2 @PCL films, regardless of the concentration of glucose in the medium, the release mechanism, given the value of the Korsmeyer–Peppas exponent being higher than 1 ( Figure 5 a), was classified as non-Fickian super case II diffusion [ 59 ]. This type of diffusion defies Fick’s law owing to a nonlinear function of the mean squared displacement versus time and applies to a case where the diffusion is very fast compared with the polymer chain relaxation rate [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Uskoković

2023

Materials

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Type 1 diabetes is caused by the inability of the pancreatic beta cells to produce sufficient amounts of insulin, an anabolic hormone promoting the absorption of the blood glucose by various cells in the body, primarily hepatocytes and skeletal muscle cells. This form of impaired metabolism has been traditionally treated with subcutaneous insulin injections. However, because one such method of administration does not directly correspond to the glucose concentrations in the blood and may fail to reduce hyperglycemia or cause hypoglycemia, the delivery of insulin in a glucose-dependent manner has been researched intensely in the present and past. This study tested the novel idea that the supplementation of polymeric reservoirs containing insulin with metallic nanoparticle precursors responsive to the redox effect of glucose could be used to create triggers for the release of insulin in direct response to the concentration of glucose in the tissue. For that purpose, manganese oxide nanoparticles were dispersed inside a poly(ε-caprolactone) matrix loaded with an insulin proxy and the resulting composite was exposed to different concentrations of glucose. The release of the insulin proxy occurred in direct proportion to the concentration of glucose in the medium. Mechanistically, as per the central hypothesis of the study, glucose reduced the manganese cations contained within the metal oxide phase, forming finer and more dissipative zero-valent metallic nanoparticles, thus disrupting the polymeric network, opening up pores in the matrix and facilitating the release of the captured drug. The choice of manganese for this study over other metals was justified by its use as a supplement for protection against diabetes. Numerical analysis of the release mechanism revealed an increasingly nonlinear and anomalous release accompanied by a higher diffusion rate at the expense of chain rigidity as the glucose concentration increased. Future studies should focus on rendering the glucose-controlled release (i) feasible within the physiological pH range and (ii) sensitive to physiologically relevant glucose concentrations. These technical improvements of the fundamental new concept proven here may bring it closer to a real-life application for the mitigation of symptoms of hyperglycemia in patients with diabetes.

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“…Explanations given by the authors referred to a number of thermodynamic considerations, such as the surface energy and solubility of precursor powders with respect to their crystalline or amorphous conditions. The follow-up article from 2019 [ 39 ] focused on elucidating the characteristics of this mechanism of drug release in the same system of cements comprising HAp1 and HAp2 at different proportions. Basic considerations for the investigated cements were the same as in the previously described work [ 38 ].…”

Section: General Matrix Featuresmentioning

confidence: 99%

“…The initial rate was higher for vancomycin and this was explained in terms of the water solubility of vancomycin, which is 10-fold higher than that for ciprofloxacin. Another comparison between vancomycin and ciprofloxacin was performed in an experiment described in two works by the group of Uskoković [ 38 , 39 ]. In these works, both drugs were loaded inside different CPC matrices, indicated as HAp1, HAp2 and their combinations at different ratios, namely 85:15 HAp1:HAp2 and 50:50 HAp1:HAp2.…”

Section: Drug Typementioning

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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Mechanism of formation governs the mechanism of release of antibiotics from calcium phosphate nanopowders and cements in a drug-dependent manner

Abstract: History of formation of the carrier affects the release mechanism, which is drastically dependent on the identity of the drug.

Cited by 28 publications

References 45 publications

Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration

Supplementation of Polymeric Reservoirs with Redox-Responsive Metallic Nanoparticles as a New Concept for the Smart Delivery of Insulin in Diabetes

Factors influencing the drug release from calcium phosphate cements

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