A biokinetic model for nickel released from cardiovascular devices

Saylor, David M.; Adidharma, Lingga; Fisher, Jeffrey W.; Brown, Ronald P.

doi:10.1016/j.yrtph.2016.05.019

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…Instead, we adopted a continuum approach and approximated the core/shell coating layer as a biphasic material, providing two independent routes of transport for each drug. These two routes could result from surface preparation methods and may correspond to the drug phases being either fully embedded within the coating layer (slow release) or connected to the surface by pores or other defects (fast release) 34 .…”

Section: Mathematical Modeling Of Drug Release In Vitromentioning

confidence: 99%

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Wang

Huang

et al. 2018

NPG Asia Mater

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In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the antiproliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease.

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Section: Mathematical Modeling Of Drug Release In Vitromentioning

confidence: 99%

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Wang

Huang

et al. 2018

NPG Asia Mater

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“…An example of a semi-empirical approach is the work of Tzafriri et al [13] where a two-part equation involving an exponential and a √ t term is used to describe release of surface-connected drug and percolating drug, respectively. This biphasic approach has also been adopted in other applications, such as nickel release from an oxide layer [25].…”

Section: In Vitro Drug Elution Kineticsmentioning

confidence: 99%

Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance

McKittrick

McKee

Kennedy

et al. 2019

Journal of Controlled Release

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In this study, we developed a predictive model of in vivo stent based drug release and distribution that is capable of providing useful insights into performance. In a combined mathematical modelling and experimental approach, we created two novel sirolimus-eluting stent coatings with quite distinct doses and release kinetics. Using readily measurable in vitro data, we then generated parameterised mathematical models of drug release. These were then used to simulate in vivo drug uptake and retention. Finally, we validated our model predictions against data on drug kinetics and efficacy obtained in a small in vivo evaluation. In agreement with the in vivo experimental results, our mathematical model predicted consistently higher sirolimus content in tissue for the higher dose stents compared with the lower dose stents. High dose stents resulted in statistically significant improvements in three key efficacy measures, providing further evidence of a basic relationship between dose and efficacy within DES. However, our mathematical modelling suggests a more complex relationship is at play, with efficacy being dependent not only on delivering an initial dose of drug sufficient to achieve receptor saturation, but also on the consequent drug release rate being tuned to ensure prolonged saturation. In summary, we have demonstrated that our combined in vitro experimental and mathematical modelling framework may be used to predict in vivo DES performance, opening up the possibility of an in silico approach to optimising the drug release profile and ultimately the effectiveness of the device.

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“…The main objectives of the nonclinical evaluation of biotherapeutics are: (1) identification of target organs for toxicity and to determine whether the toxicity is reversible after the treatment has stopped; (2) identification of a safe starting dose for human Phase I clinical trials and subsequent dose escalation schemes, which is highly dependent on the patient population for the Phase I trial(s); and (3) provide information to monitor safety parameters in clinical trials [ 5 , 17 , 18 , 19 , 20 ]. Key factors that must be considered for mAb development are: knowledge of the antigen target biology and location of the target, both desired and undesired.…”

Section: Nonclinical Safety Evaluations For Mabsmentioning

confidence: 99%

“…Additional factors include pharmacological properties and mechanism of action of the therapeutic mAb; exposure–response relationships; estimates of pharmacokinetic parameters and how these may relate to the determination of a recovery period; and clearly defined clinical trial design and potential characteristics and co-morbidities of patients [ 5 ]. In the development process, non-clinical studies rarely identify toxicities that are dose limiting and the selection of a pharmacologically relevant species is of paramount importance [ 4 , 5 , 6 , 17 , 18 , 19 , 20 ]. Accordingly, the lack of toxicity related to significant decreased or a lack of pharmacological action in the model negates the use of lack of toxicity to be used as a measure of safety.…”

Section: Nonclinical Safety Evaluations For Mabsmentioning

confidence: 99%

Biotherapeutics: Challenges and Opportunities for Predictive Toxicology of Monoclonal Antibodies

Johnson

2018

IJMS

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Biotherapeutics are a rapidly growing portion of the total pharmaceutical market accounting for almost one-half of recent new drug approvals. A major portion of these approvals each year are monoclonal antibodies (mAbs). During development, non-clinical pharmacology and toxicology testing of mAbs differs from that done with chemical entities since these biotherapeutics are derived from a biological source and therefore the animal models must share the same epitopes (targets) as humans to elicit a pharmacological response. Mechanisms of toxicity of mAbs are both pharmacological and non-pharmacological in nature; however, standard in silico predictive toxicological methods used in research and development of chemical entities currently do not apply to these biotherapeutics. Challenges and potential opportunities exist for new methodologies to provide a more predictive program to assess and monitor potential adverse drug reactions of mAbs for specific patients before and during clinical trials and after market approval.

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A biokinetic model for nickel released from cardiovascular devices

Cited by 15 publications

References 23 publications

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance

Biotherapeutics: Challenges and Opportunities for Predictive Toxicology of Monoclonal Antibodies

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