High performance simulation of drug release model and mass transport model by using hybrid platform

The controlled drug delivery in drug eluting stents exerts an important influence in decreasing restenosis in intravascular stenting. These stents are coated with drug to avoid the re-narrowing of the arterial wall. The drug is directly associated with the original bare metal stents. Drug eluting stents have plus point of a flexible time delivery of a curative drug to the neighboring arterial tissue. It treats the required injuries efficiently having negligible systemic drug interaction. This thesis aims to develop a mathematical model for describing the procedure of drug distribution from stent coating and from arterial wall. For this purpose, a mathematical model of two phase is presented to simulate the transportation of drug between coating and arterial tissue. This two-phase model explores the impact of non-dimensional parameters such as solid liquid mass transfer rate , ratio of accessible void volume to solid volume and Peclet number on drug release and mass concentrations from coating and tissue layers. For better understanding a 2D mathematical model of biodurable stent coating is developed, where the intravascular distribution of drug from an implanted drug eluting stent in arterial wall is simulated. The model integrates reversible drug binding and diffusion of drug in the stent coating. The arterial wall and coating drug diffusivities are examined for the impact of arterial drug uptake and drug release in the coating. The diffusion coefficient of drug , the diffusion coefficients of wall , , and strut embedment play an important role to regulate the drug release. Moreover, a 3D model of mass concentrations and drug release from the cross section of artery is investigated. The impact of advective and diffusive velocities is explored and these forces can be used to control the mass concentrations of drug. FEM and FDM is used for spatial and temporal discretization of model equations. The sequential and parallel algorithms are developed for numerical simulations. Furthermore, the motivation for using GPU accelerators with CUDA is explained to handle computational complexities. A hybrid CPU/GPU algorithm for the proposed models is designed and satisfactory results for parallel performance indicators such as; speedups Sp, temporal performance Tp, efficiency Ep and effectiveness Fp are obtained. The CN method gives better sequential results because it has less RMSE than GD and BD methods. However, the BD method gives good results for parallel indicators because it involves less computation than GD and CN methods. The sequential and parallel performance of BM method is better as compared to NM and PM methods. The BM method has least RMSE for both sequential and parallel algorithms. The parallel performance indicators Sp, Tp, Ep and Fp for BM method gives better performance than the other methods. Therefore, it is a superior method than the NM and PM methods. Hybrid algorithms are more efficient in large-scale problem simulations as shown in parallel performance results. The governing models in this research provide the basis of a design tool for studying and calculating drug distribution in coating and arterial wall in the application of stent-based drug delivery. The models propose in this research are used for monitoring purpose and to determine drug release, mass transport, visualization and observation. The simulations support to offer a good perception into the potential effects of different parameters such as γ1, e1, Pe, Dc, Dw, Dwx, Dwy and strut embedment can affect the efficiency of drug release

Zein-based smart coatings for drug-eluting stents: investigations via static and microfluidic approaches

Coronary heart disease is currently responsible for a significant percentage of global mortality in developed and developing nations alike. This occurrence takes place despite the advancement in medical technology and improved treatment options, such as stenting procedures. Due to complications with restenosis and stent thrombosis that are associated with current commercial stents, there has been a growing interest in stent research and development in order to eradicate the causes of such clinical events. The selection of an antioxidant, non-thrombogenic coating has been a major obstacle to the development of drug-eluting stents (DES), and, to date, a truly biocompatible stent platform remains elusive. Moreover, there is a need to assess stent coatings within an in vitro platform prior to in vivo and clinical studies in order to minimize adverse effects. Even if considerable progress has been made over the last two decades in the development of flow chambers to monitor and study thrombus formation outside of the circulation, blood-material interactions are still little investigated under static and dynamic modes. In order to avoid some of the drawbacks of synthetic polymers, such as their undesirable degradation products, long-lasting presence, or potential biocompatibility issues, the aim of this PhD thesis was to investigate zein as a green and abundant plant-derived protein as a coating material for DES applications. This study aimed to understand the potential uses of zein as a controlled release matrix for drug delivery systems, in addition to developing a microfluidic platform to assess the behavior and hemocompatibility of the proposed plant-based stent coatings under flow conditions

Biopolymers in Drug Delivery and Regenerative Medicine

Biopolymers including natural (e.g., polysaccharides, proteins, gums, natural rubbers, bacterial polymers), synthetic (e.g., aliphatic polyesters and polyphosphoester), and biocomposites are of paramount interest in regenerative medicine, due to their availability, processability, and low toxicity. Moreover, the structuration of biopolymer-based materials at the nano- and microscale along with their chemical properties are crucial in the engineering of advanced carriers for drug products. Finally, combination products including or based on biopolymers for controlled drug release offer a powerful solution to improve the tissue integration and biological response of these materials. Understanding the drug delivery mechanisms, efficiency, and toxicity of such systems may be useful for regenerative medicine and pharmaceutical technology. The main aim of the Special Issue on “Biopolymers in Drug Delivery and Regenerative Medicine” is to gather recent findings and current advances on biopolymer research for biomedical applications, particularly in regenerative medicine, wound healing, and drug delivery. Contributions to this issue can be as original research or review articles and may cover all aspects of biopolymer research, ranging from the chemical synthesis and characterization of modified biopolymers, their processing in different morphologies and hierarchical structures, as well as their assessment for biomedical uses

Rheology and Processing of Polymers

This book covers the latest developments in the field of rheology and polymer processing, highlighting cutting-edge research focusing on the processing of advanced polymers and their composites. It demonstrates that the field of rheology and polymer processing is still gaining increased attention. Presented within are cutting-edge research results and the latest developments in the field of polymer science and engineering, innovations in the processing and characterization of biopolymers and polymer-based products, polymer physics, composites, modeling and simulations, and rheology

BIOACTIVE POLY(BETA-AMINO ESTER) BIOMATERIALS FOR TREATMENT OF INFECTION AND OXIDATIVE STRESS

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular toxicity, and material morphology. Using these fundamentals of covalent drug-addition into biodegradable polymers, we addressed two problems that exist with the treatment of patients with high-risk wound-sites, namely non-biodegradability that require second-surgeries, and free-loaded antibiotic systems where partially degraded materials fall below the minimum inhibitory concentration, allowing biofilm proliferation. Our in situ polymerizable, covalently-bound vancomycin hydrogel provided active antibiotic degradation products and drug release which closely followed the degradation rate over tunable periods. With applications of antioxidant delivery, we continued with this concept of covalent drug addition and modified a PBAE, utilizing a disulfide moiety to mimic redox processes which glutathione/glutathione disulfide performs. This material was found to not only be hydrolytically biodegradable, but tunable in reducibility through cleavage of the disulfide crosslinker, forming antioxidant groups of bound-thiols, similar to drugs currently used in radioprotective therapies. The differential cellular viability of degradation products containing disulfide or antioxidant thiol forms was profound, and the antioxidant form significantly aided cellular resistance to a superoxide attack, similar to that of a radiation injury. Pathophysiological oxidation in the form of radiation injury or oxidative stress based diseases are often region specific to the body and thus require specific targeting, and nanomaterials are widely researched to perform this. Utilizing a tertiary-amine base-catalyst, we were able to synthesize a high drug content (20-26 wt%) version of the disulfide PBAE previously unattainable. The reduced version of this material created a linear-chain polymer capable of single-emulsion nanoparticle formulation for use with intravenous antioxidant delivery applications instead of local

Preparation of biofunctional textiles by surface functionalization based on the nanoencapsulation technique.

L'abstract è presente nell'allegato / the abstract is in the attachmen

Chapter 34 - Biocompatibility of nanocellulose: Emerging biomedical applications

Nanocellulose already proved to be a highly relevant material for biomedical applications, ensued by its outstanding mechanical properties and, more importantly, its biocompatibility. Nevertheless, despite their previous intensive research, a notable number of emerging applications are still being developed. Interestingly, this drive is not solely based on the nanocellulose features, but also heavily dependent on sustainability. The three core nanocelluloses encompass cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). All these different types of nanocellulose display highly interesting biomedical properties per se, after modification and when used in composite formulations. Novel applications that use nanocellulose includewell-known areas, namely, wound dressings, implants, indwelling medical devices, scaffolds, and novel printed scaffolds. Their cytotoxicity and biocompatibility using recent methodologies are thoroughly analyzed to reinforce their near future applicability. By analyzing the pristine core nanocellulose, none display cytotoxicity. However, CNF has the highest potential to fail long-term biocompatibility since it tends to trigger inflammation. On the other hand, neverdried BNC displays a remarkable biocompatibility. Despite this, all nanocelluloses clearly represent a flag bearer of future superior biomaterials, being elite materials in the urgent replacement of our petrochemical dependence