Modeling of Nano-carriers for Vascular-targeted Delivery for Blood Clots Treatment

Nanoparticles have become one of the emerging and promising technologies that revolutionized the medical field’s future on which has received much attention from the scientific community and researchers. Nanotechnology-based targeted drug delivery has a high capacity for loading large amounts of anticoagulants drug to dissolve clots in a safe manner without affecting healthy blood vessels. This paper seeks to provide a better understanding of both the anticoagulant drug release process and the coagulation eliminating process by simulating each process using chemical reaction engineering, moving mesh, and convection-diffusion equation modules. This study adds to a growing corpus of research showing that nanotechnology empowers in treating blood clots within 2-4 hours. In addition, these results cast a new light on a better understanding of the anticoagulation drug diffusion from both spheres and multiply-twinned nanoparticles besides the reduction of clots growth and how it dissolved over time.


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The nanoparticle-based drug delivery researches have a long tradition. Today, nanotechnology 22 become at the forefront of the medical research basics that are attracting many researcher's attention.

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There are growing appeals for investigating the use of nanotechnology in the treatment and 24 prevention of the blood clot. As a rule, thrombosis is a term used to express the blood clots or blood 25 clump that is caused due to the blood transformation from a liquid state to a semi-solid or gel-like 26 state [1]. The sudden interruption of blood flow due to travel of blood clot (embolus) further down 27 the arteries that become stuck and adhered to the artery wall and then; prevents the flow of blood to 28 an organ or part of the body known as an "arterial embolism".

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To demonstrate, both nanoparticles and polymers can be integrated into many materials and 30 applications such as biotechnology, pharmaceuticals, protective coatings, chemical catalysis and the 31 most important of which is drug delivery [2,3]. Therefore, one of the most important basics that must 32 be known and considered when using nanoparticles in particular for medical applications is the

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Indeed, one of the problems with traditional methods of treating blood clots is the drug 45 ineffectiveness in removing the blood clot within hours, which leads to preventing blood flow inside the blood vessels and then the death of tissue because the insufficient blood and oxygen that reach them. In addition to the large dose of medication provided to the patient.

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Most of the theories of blood clot removal are however focused on explaining the methods to 49 treat, prevent blood clots, their signs, symptoms, causes as well as the available drugs of treatments 50 and its side effects. In the past few decades, nanotechnology for drug delivery systems and drug-51 release kinetics have played an important role in the medical field especially in the diagnosis and 52 treatment of various diseases such as cancer detection, targeting, DNA delivery and the biochemical 53 sensors [11,12]. A study was held at Harvard University's Wyss Institute to treat the coagulation 54 disorders using nanoparticles, where it secretes the drug in the place of clotting when it is exposed 55 to high shear pressure due to the narrowing of the blood vessels due to stroke [13]. Other researchers 56 [14,15] have used magnetic nanoparticles to control the medication to dissolve the clot. The study 57 concluded that this mechanism is highly effective and effective in dissolving clots within hours safely.

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A clinical study conducted to suggested a classification system to predicts the clot type, number of

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Despite all researches that have been done; still, there are no studies have focused on the drug 67 release kinetics simulation in the blood clot site, in addition, to examine the drug release rate as well 68 as the thrombosis elimination over time and this is what this study attempting to shows. Also, there 69 are no studies that focused specifically on investigating the diffusion of the drug from different forms 70 of particles, and this is what the study will achieve for both the spherical morphology and the 71 multiple-twinned of the prism-shape to determine which is optimal for application in the treatment 72 of blood clots. So, this paper considers and focuses on the arterial blood clot (thrombosis) and we 73 simulated the antithrombotic agent delivery and release to the blocked artery in the artery using    Either the thrombus blocks blood flow and this closes the blood vessel completely and is known as 91 an occlusive thrombus [28]. As for the third type, it is a choice that extends and multiplies along the

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This model consists of a blood clot, polymeric nanoparticles with sphere and prism-shapes, and 127 an arterial vessel as shown in (Figure 2 A, B). The reaction kinetics of the drug is analyzed in two 128 parts. The first part is represented in 0D in which the engineering interface for the reaction is used 129 and allows the pharmacokinetics to be resolved to interact with the drug over time and describe the

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Where D is the drugs i diffusion coefficient in the respective medium (m 2 /s) and is the drugs 142 i rate expression in the medium (mol/(m 3 ·s)).

Moving Mesh and Convection-Diffusion Equation Modules
144 The diffusion equation was combined with the moving mesh node for modeling to simulate the 145 thrombosis removal and shrinking during the time. The model consists of two-dimensional geometry 146 that represents both thrombus, nanoparticles and artery as shown in (Figure 3). This clot field extends 147 below the artery layer and under the shear pressure proportion that stimulates nanocarriers to start 148 releasing the drug at the thrombus site and start dissolving and removing it.

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The materials of the model were selected automatically and the mesh was chosen to be a size

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Here the release of the drug has been studied for an hour and 30 minutes, and most often the

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The Computational modeling adopted in this study is one of the new sources that provide a In (Figure 8 A) in the 70th minute, 28% were fired, but in (Figure 8 B)

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To clarify, when developing drug delivery systems for therapeutic applications, it is very 225 important to take into account both the drug biological decomposition in addition to the release 226 profile for this drug which in turn contributes to improving and maximizing the therapeutic effect.

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The drug's solubility and diffusion can accurately determine the effectiveness of these drugs as well 228 as their active ingredients. As shown in (Figure 9 A,

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As an illustration, the accurate design of nanoparticles greatly affects the place and time of the 238 drug's release due to the difference in sensitivity of these particles to body temperature, pH, pressure 239 and enzymes. If we assume that, both of the two shapes adopted in the design of nanoparticles in this 240 study release the same amount of medicine at the same time, the most important thing is to know the 241 amount of the drug released is to know the concentration percentage for the diffused drug in the 242 target site. The drug properties are largely controlled by both the shape and design of nanoparticles.

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The lower the amount of the medication that is released versus an increase in its concentration, the 244 therapeutic efficacy of this drug will increase as well as the optimization of the patient's compliance 245 with this drug in less time. When both sphere and multiply-twinned nanoparticles shape are 246 compared, the concentration of the drug in (Figure 10 B), which appears in red, is higher than the 247 concentration of the drug in the spherical shape (Figure 10 A).

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The concentration of the drug inside the nanoparticles depends on the particle shape and the     After 30 min later in the 80th min, there was only clots take less than 30% from the total channel 348 area as shown in (Figure 21 A) and after 1:30 min the blood can flow in a good manner and this 349 suggests that the 10% of the remained clots as shown in (Figure 21 B)

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the multiply-twinned shape was the best shape compared with the sphere as it showed the highest 369 concentration of the drug in the thrombosis site.