Nanoparticles offer an ideal opportunity for the efficient local anesthetic drug delivery required during and after ocular procedures. Currently available local anesthetic drugs are short acting, which may prevent adequate ocular pain control. Therefore, development of sustained controlled release anesthetic devices for pain control over a relatively short period (up to 48 h) potentially meets various opthalmological analgesic requirements. This study presents preliminary findings for drug delivery using poly(sebacic acid) (PSA) nanoparticles for tetracaine and lidocaine administration. Tetracaine- or lidocaine-loaded PSA nanoparticles were prepared using a double emulsion methodology. Release profiles were similar for both formulations, with 50% cumulative release achieved after 17 h and 23 h for tetracaine and lidocaine, respectively. The release profiles were studied, and data obtained from in vitro experiments were fit to different mathematical models. Based on mathematical models used in this study, drug release from all PSA-based formulations was diffusion-controlled, best described by the Higuchi model. Based on preliminary experiments, a hybrid formulation providing a burst effect was designed to counter the fast adsorption of drug expected in the physiological system. This was achieved by coating the lidocaine-loaded PSA nanoparticles with a gelatin/lidocaine layer. The coating provided accelerated lidocaine release, with 50% cumulative release obtained as early as 7 h compared to 23 h for uncoated nanoparticles. This formulation provided a triphasic release that can treat different pain levels at predetermined timelines. Our results provide new insight into the benefits of using polyanhydrides as a platform for drug delivery in ophthalmology.

Abstract Local inflammation of the endothelium is associated with a plethora of cardiovascular diseases. Vascular‐targeted carriers (VTCs) have been advocated to provide focal effective therapeutics to these disease sites. Here, we examine the design of functionalized nanoparticles (NPs) as VTCs that can specifically localize at an inflamed vessel wall under pathological levels of high shear stress, associated for example with clinical (or in vivo) conditions of vascular narrowing and arteriogenesis. To test this, carboxylated fluorescent 200 nm polystyrene particles were functionalized with ligands to activated endothelium, that is, an E‐selectin binding peptide (Esbp), an anti ICAM‐1 antibody, or using a combination of both. The functionalized NPs were investigated in vitro using microfluidic models lined with inflamed (TNF‐α stimulated) and control endothelial cells (EC). Specifically, their adhesion was monitored under different relevant wall shear stresses (i.e., 40–300 dyne/cm2) via real‐time confocal microscopy. Experiments reveal a significantly higher specific adhesion of the examined functionalized NPs to activated EC for the window of examined wall shear stresses. Moreover, particle adhesion correlated with the surface coating density whereby under high surface coating (i.e., ~10,000 molecule/particle), shear‐dependent particle adhesion increased significantly. Altogether, our results show that functionalized NPs can be designed to target inflamed endothelial cells under high shear stress. Such VTCs underscore the potential for attractive avenues in targeting drugs to vasoconstriction and arteriogenesis sites.

Coronary stenosis due to atherosclerosis, the primary cause of coronary artery disease, is generally treated by balloon dilatation and stent implantation, which can result in damage to the endothelial lining of blood vessels. This leads to the restenosis of the lumen as a consequence of migration and proliferation of smooth muscle cells (SMCs). Nitric oxide (NO), which is produced and secreted by vascular endothelial cells (ECs), is a central anti-inflammatory and anti-atherogenic player in the vasculature. The goal of the present study was to develop an enzymatically active surface capable of converting the prodrug l-arginine, to the active drug, NO, thus providing a targeted drug delivery interface. NO synthase (NOS) was chemically immobilized on the surface of a stainless steel carrier with preservation of its activity. The ability of this functionalized NO-producing surface to prevent or delay processes involved in restenosis and thrombus formation was tested. This surface was found to significantly promote EC adhesion and proliferation while inhibiting that of SMCs. Furthermore, platelet adherence to this surface was markedly inhibited. Beyond the application considered here, this approach can be implemented for the local conversion of any systemically administered prodrug to the active drug, using catalysts attached to the surface of the implant.

Biodegradable constructs, providing both mechanical support to growing tissues and timed release of biological agents, are highly desired in tissue engineering. This study aimed to develop a platform technology that responds to these challenges. Accordingly, we report herein on model systems in which microspheres of poly(suberic anhydride), containing all - trans retinoic acid (atRA), and poly( d,l -lactic acid- co -glycolic acid), containing bovine serum albumin (BSA), were co-sintered at room temperature, using a solvent/nonsolvent mixture. These scaffolds release about 60% of atRA and negligible amounts of BSA within the first five days, followed by slower and steady release of BSA. They have pores of 150–500 μm and a compressive modulus of 200 kPa. Myoblasts and fibroblasts were seeded on the loaded scaffolds and both showed enhanced proliferation rates. Based on sound thermodynamic principles of polymer science, this technology demonstrates an as yet unachieved degree of versatility. It allows for the tailoring of “intelligent” scaffolds that preserve the integrity of the incorporated agents and of advanced modalities to release various drugs in a scheduled manner.

We provide a comparison of two classes of fluid conveying materials systems: hard, structural materials for infrastructure systems, and soft, and functional materials in the human body. They are part of two vital systems indispensable for human life: water pipelines (WP) and blood vessels (BV). A comparative assessment of their physical and chemical characteristics, their structures and functions, their deterioration mechanisms, repair procedures and protection methods is presented. Both water and blood are conveyed in tubular systems: water in steel, plastics and cement pipelines, which should be maintained free from corrosion, scaling, erosion and fouling; and blood vessels, which need to be maintained without the formation of plaques and clots, to keep blood circulating freely. This comparative analysis promotes the interaction of teachers and students from different fields of endeavor to explain and understand fundamental structures, technologies and processes, addressing regular materials in industry in parallel to the biological world of the human body.

Both metallic corrosion and biological respiration involve oxidation reduction reactions, taking place upon electron transfer between the participating entities. Metals corrode as a consequence of their tendency to return to the oxide state prevailing in the original ores. Corrosion occurs by reduction of dissolved oxygen in neutral pH solutions, or by reduction of H(+) ions in acidic solutions. The involvement of oxygen and redox reactions is also essential for sustaining life in biological systems. Biological respiration in humans relies on the oxidation of carbohydrates, fats and amino acids as a part of the vital network of metabolic processes that generate the energy necessary to maintain normal body function and temperature. In plant systems the biological 'respiration' process of photosynthesis, which involves chlorophyll, is a major source of oxygen on the planet. For example, in human biological systems, unlike corrosion processes in metals, oxygen transport by blood is carried out by haemoglobin as the essential process of human respiration. Haemoglobin is a tetrameric protein located in the red blood cells, containing porphyrin-bound Fe(2+). Haemoglobin picks up oxygen in the lungs, carries it to the tissues and releases it there, where it is actually used. On its way back, haemoglobin picks up the metabolic CO(2) produced in the tissues and releases it into the lungs. In photosynthesis the chlorophyll molecule is the inverse analog to haemoglobin; both molecules are porphyrins with the difference of central metal atoms being Fe in haemoglobin and Mg in chlorophyll. In this report similarities and disparities between metallic corrosion and biological respiration are presented, taking into account the respective reactants, products and catalysts. This comparative study allows for the interaction between teachers and students, in order to explain the similarities and diversities of the fundamentals of natural processes such as metallic corrosion and biological respiration. This paper covers elements from the mineral, animal and vegetable kingdom, with a comparative approach.

A Research-Driven Resource on Building Biochemical Systems to Perform Information Processing Functions Information Processing by Biochemical Systems describes fully delineated biochemical systems, organized as neural networktype assemblies. It explains the relationship between these two apparently unrelated fields, revealing how biochemical systems have the advantage of using the "language" of the physiological processes and, therefore, can be organized into the neural networktype assemblies, much in the way that natural biosystems are. A wealth of information is included concerning both the experimental aspects (such as materials and equipment used) and the computational procedures involved. This authoritative reference: Addresses network-type connectivity, considered to be a key feature underlying the information processing ability of the brain Describes novel scientific achievements, and serves as an aid for those interested in further developing biochemical systems that will perform information-processing functions Provides a viable approach for furthering progress in the area of molecular electronics and biocomputing Includes results obtained in experimental studies involving a variety of real enzyme systems Information Processing by Biochemical Systems is intended for graduate students and professionals, as well as biotechnologists.

Chapter 2 Background and Goals of this Study Orna Filo, Orna FiloSearch for more papers by this authorNoah Lotan, Noah LotanSearch for more papers by this author Book Author(s):Orna Filo, Orna FiloSearch for more papers by this authorNoah Lotan, Noah LotanSearch for more papers by this author First published: 09 December 2009 https://doi.org/10.1002/9780470552681.ch2 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Information Processing by Biochemical Systems: Neural Network–Type Configurations RelatedInformation

Cartilage substitutes are needed to replace cartilage tissue, damaged in accident,, or by pathologies (e.g., osteoarthritis). Treatment by total hip replacement has disadvantages, particularly due to immunological reaction to the implant's wear debris. One promising alternative is to replace damaged cartilage with substitutes based on hydrogel-type material, designed to mimic the structure and properties of cartilage. The development of such a substitute must consider a wide spectrum of requirements. In this study, we addressed one aspect of this development namely the preparation and. investigation of hydrogels exhibiting the required mechanical characteristics. To this aim, poly(ethylene glycol) (PEG) hydrogels and amphiphilic interpenetrating polymer networks (IPNs) of PEG with poly(methyl methacrylate) (PMMA) were prepared and characterized for their mechanical and swelling properties. Twenty-seven types of hydrogels were synthesized, differing in their composition: PEG molecular weight, crosslink density, and PMMA volume fraction. The properties measured were water content, compression modulus, strength, fatigue durability, and poroelastic properties (hydraulic permeability and equilibrium modulus). All were investigated as functions of hydrogel's composition. Results show that lower PEG M,,,, higher crosslink densities and higher PMMA fraction, all lead to higher modulus and lower water content, and that these properties can be controlled independently by proper choice of ingredients. Introduction of IPN greatly improved the hydrogels' strength. No reduction in the compression modulus resulting from fatigue damage was evident. Poroelastic properties varied nonmonotonously with structural characteristics. Seven types of the hydrogels were found to fit cartilage in their water content, modulus, and poroelastic properties. (c) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 112: 390-401, 2009

"Corrosion of polymeric biomaterials." Corrosion Engineering, Science and Technology, 42(4), p. 281

AbstractThe possibility of using human blood for transfusion is limited by requirements of blood‐typing, the danger of transmitting certain diseases, and a short shelf life of liquid blood. These limitations and the wide range of applications of blood substitutes have fueled a worldwide search for safe, effective, and universal blood substitute materials.One major route to avoid the problems associated with blood (i.e., AIDS, Hepatitis, etc.) involves the use of isolated human hemoglobin (Hb) because of its high capacity of oxygen and hemocompatibility. However, cell‐free Hb has to be either molecularly modified or encapsulated in order to prevent its dissociation into dimers, decrease the high oxygen affinity, and increase the retention time in circulation. This route of research requires the use of specifically designed cross‐linker reagents necessary to modify the Hb protein.With molecular engineering techniques, a new family of cross‐linking reagents was developed, based on nicotinamide‐adenine dinucleotide (NAD) derivatives. One of the reagents designed, namely oxidized beta‐NAD (o‐NAD), was reacted with deoxyHb to produce NAD‐derivatized hemoglobin (HbNAD). The latter was further polymerized to yield poly‐HbNAD.Macroscopic properties of HbNAD and poly‐HbNAD were studied. From the results obtained, it is evident that poly‐HbNAD possesses a physiological oxygen‐carrying capacity and oncotic characteristics similar to whole blood. These properties make poly‐HbNAD a viable potential candidate as a resuscitation fluid.

The analysis deals with an integrated system in which enzymic de-polymerization of a macromolecular substrate and concomitant separation of the reaction products take place. The enzyme is immobilized within a packed-bed reactor and products are separated by ultrafiltration. A compartmental model was set up and used to simulate the performance of the system in terms of yield, purity, and productivity of the monomer obtained, and as a function of the system operating mode (batch or continuous), recirculation ratio, enzyme mode of action (preferred attack or exo-type), and initial polymer concentration. Results, calculated using the analytical model, are in good agreement with our experimental findings concerning the depolymerization of inulin by exo-inulinase. Future applications include engineering design of the system and optimization of its operational parameters.

Enzyme-Based Logic Gates (ENLOGs) are key components in bio-molecular systems for information processing. This report and the previous one in this series address the characterization of two bio-molecular switching elements, namely the alpha-chymotrypsin (alphaCT) derivative p-phenylazobenzoyl-alpha-chymotrypsin (PABalphaCT) and its inhibitor (proflavine), as well as their assembly into a logic gate. The experimental output of the proposed system is expressed in terms of enzymic activity and this was translated into logic output (i.e. "1" or "0") relative to a predetermined threshold value. We have found that an univalent link exists between the dominant isomers of PABalphaCT (cis or trans), the dominant form of either acridine (proflavine) or acridan and the logic output of the system. Thus, of all possible combinations, only the trans-PABalphaCT and the acridan lead to an enzymic activity that can be defined as logic output "1". The system operates under the rules of Boolean algebra and performs as an "AND" logic gate.