Shady Farah

Drug eluting stents: developments and current status.

Coronary stenting has revolutionized current perspective of coronary artery disease management. Bare-metal stents (BMS) were introduced in 1994, but long-term results have been shattered by the dual problems of in-stent restenosis (ISR) and stent thrombosis associated with BMS. Though stent thrombosis became much less frequent after the introduction of antiplatelet therapy, restenosis however remained as a significant problem. Intense work on stent development has successfully led to the introduction of drug-eluting stents (DES) in 2002, as an effort to address restenosis problem. First generation DES (sirolimus and paclitaxel eluting) were introduced first and found to be more effective than BMS. The use of first generation DES dealt with the problem of restenosis. But, despite early successes, uncertainty remains on the overall safety, especially for late adverse clinical events such as stent thrombosis. Thus, the second generation (everolimus and zotarolimus eluting) stents were developed and introduced with lower thrombosis rates. Today, in the search for improving the performance of available DES various developments and clinical studies are ongoing. Research and developments is primarily centred on increasing the long-term safety and efficacy of stents.

Biodegradable Polymers Derived From Amino Acids

In the past three decades, the use of polymeric materials has increased dramatically for biomedical applications. Many α-amino acids derived biodegradable polymers have also been intensely developed with the main goal to obtain bio-mimicking functional biomaterials. Polymers derived from α-amino acids may offer many advantages, as these polymers: (a) can be modified further to introduce new functions such as imaging, molecular targeting and drugs can be conjugated chemically to these polymers, (b) can improve on better biological properties like cell migration, adhesion and biodegradability, (c) can improve on mechanical and thermal properties and (d) their degradation products are expected to be non-toxic and readily metabolized/excreted from the body. This manuscript focuses on biodegradable polymers derived from natural amino acids, their synthesis, biocompatibility and biomedical applications. It is observed that polymers derived from α-amino acids constitute a promising family of biodegradable materials. These provide innovative multifunctional polymers possessing amino acid side groups with biological activity and with innumerous potential applications.

Carrier free rapamycin loaded drug eluting stent: In vitro and in vivo evaluation

In the search for improving the performance of drug eluting stent (DES) various developments are in progress worldwide including use of carrier free DES, use of biodegradable polymers, biodegradable stents etc. In this work, carrier free-rapamycin (RM) coated DES has been prepared, and evaluated by in vitro and in vivo procedures necessary for clinical development. In vitro drug release from the developed stents was carried in different release media, normal saline-isopropanol (NS-IP), phosphate buffer (PB), phosphate buffer saline (PBS) and in human plasma. Simultaneously, drug released at site of implantation and biocompatibility of developed stents was determined after subcutaneous implantation in the SD rats. Developed stent coating method enables fabrication of controllable and homogeneous crystalline RM coatings on stent scaffolds. Continuous release of RM was observed in different release conditions with different release rate, maximum in NS-IP and least in PB. Similarly, after subcutaneous implantation of these stents, RM was found in surrounding tissues and in implanted stent up to 28 days. Biocompatibility studies showed no evidence for presence of necrosis, foreign body giant cell reaction or any type of increased severity of inflammatory reaction, proving potential of developed stents for further clinical development.

Crystalline coating of rapamycin onto a stent: Process development and characterization

Currently marketed drug eluting stents (DES) are mainly matrix based systems, with drug entrapped in a carrier system. However, biocompatibility and other issues are associated with these matrix carrier systems. An alternate approach is the use of carrier-free DES, yet preventing functionalities of the carrier. Considering this, the objective of the present contribution is to develop a novel surface crystallization procedure for rapamycin (RM) coating on metallic stent. The physicochemical principles of the crystallization and key process parameters were extensively studied for fabrication of controllable and homogeneous crystalline coatings on stent scaffolds. Stents loaded with nearly 100 μg RM were chosen as a potential therapeutic device with multilayer coating of thickness 3-5 μm. In vitro RM release from these coated stents showed constant RM release for over 90 days and stability studies proves stability of developed RM coating when exposed to different storage condition for 6 months. In conclusion, developed crystallization process was found effective for fabrication of DES with stable coating. This process has wide applications and can be further implemented for other drugs for effective local drug delivery from implantable medical devices.

Quaternary ammonium polyethylenimine nanoparticles for treating bacterial contaminated water.

This study highlights the potential application of antimicrobial quaternary ammonium nanomaterials for water disinfection. Quaternary ammonium polyethylenimine (QA-PEI) nanoparticles (NPs) were synthesized by polyethylenimine crosslinking and alkylation with octyl iodide followed by methyl iodide quaternization. Particles modified with octyldodecyl alkyl chains were also prepared and evaluated. The antimicrobial activity of QA-PEI NPs was studied after anchoring in non-leaching polymeric coatings and also in aqueous suspension. Particles at different loadings (w/w) were embedded in polyethylene vinyl acetate and polyethylene methacrylic acid coatings and tested for antimicrobial activity against four representative strains of bacteria in static and dynamic modes. Coatings embedded with fluorescent labelled particles tracked by Axioscope fluorescence microscope during the antimicrobial test indicates no particles leaching out. Coatings loaded with 5% w/w QA-PEI exhibited strong antibacterial activity. Aqueous suspension was tested and found effective for bacterial decontamination at 0.1 ppm and maintains its activity for several weeks.

Quaternary ammonium poly(diethylaminoethyl methacrylate) possessing antimicrobial activity

Quaternary ammonium (QA) methacrylate monomers and polymers were synthesized from a N-alkylation of N,N-diethylaminoethyl methacrylate (DEAEM) monomer. Linear copolymers, and for the first time reported crosslinked nanoparticles (NPs), based QA-PDEAEM were prepared by radical polymerization of the quaternized QA-DEAEM monomers with either methyl methacrylate (MMA) or a divinyl monomer. QA-PDEAEM NPs of 50-70 nm were embedded in polyethylene vinyl acetate coating. QA-polymers with N-C8 and N-C18 alkyl chains and copolymers with methyl methacrylate were prepared at different molar ratios and examined for their antimicrobial effectiveness. These coatings exhibited strong antibacterial activity against four representative Gram-positive and Gram-negative bacteria.

Morphological, spectral and chromatography analysis and forensic comparison of PET fibers

Poly(ethylene terephthalate) (PET) fiber analysis and comparison by spectral and polymer molecular weight determination was investigated. Plain fibers of PET, a common textile fiber and plastic material was chosen for this study. The fibers were analyzed for morphological (SEM and AFM), spectral (IR and NMR), thermal (DSC) and molecular weight (MS and GPC) differences. Molecular analysis of PET fibers by Gel Permeation Chromatography (GPC) allowed the comparison of fibers that could not be otherwise distinguished with high confidence. Plain PET fibers were dissolved in hexafluoroisopropanol (HFIP) and analyzed by GPC using hexafluoroisopropanol:chloroform 2:98 v/v as eluent. 14 PET fiber samples, collected from various commercial producers, were analyzed for polymer molecular weight by GPC. Distinct differences in the molecular weight of the different fiber samples were found which may have potential use in forensic fiber comparison. PET fibers with average molecular weights between about 20,000 and 70,000 g mol(-1) were determined using fiber concentrations in HFIP as low as 1 μg mL(-1). This GPC analytical method can be applied for exclusively distinguish between PET fibers using 1 μg of fiber. This method can be extended to forensic comparison of other synthetic fibers such as polyamides and acrylics.

Surface Crystallization of Rapamycin on Stents Using a Temperature Induced Process

Metallic drug eluting stents (DES) are usually prepared by coating with a drug-polymer matrix as a rate controlling diffusion barrier. However, coating materials may display numerous problems, thus carrier-free DES are desired, yet releasing drug over long period of time. For this, we are reporting a novel temperature induced (TI) crystallization process for coating rapamycin on stents. Rapamycin crystals with a defined morphology and target drug load were applied from supersaturated solution. This method enables fabrication of controllable and homogeneous crystalline coatings on stent scaffolds and allowing the drug to release for several weeks.

2 – Nanotechnology for water purification: applications of nanotechnology methods in wastewater treatment

Providing clean and affordable drinking water is one of the modern-times challenges. The world’s growing population causes water scarcity, and pollutants contaminate whatever water sources are left. Nanotechnology has provided innovative solutions for water purification. This chapter reviews nanotechnology-enabled water-treatment processes, showing how they transform our water supply and wastewater treatment. The following topics are discussed: different nanomaterials, properties, mechanisms, advantages compared to existing methods, limitations, research needs for commercialization, and toxicities of nanomaterials.

Antimicrobial evaluation of quaternary ammonium polyethyleneimine nanoparticles against clinical isolates of pathogenic bacteria.

Peritonitis is a disease caused by bacterial strains that have become increasingly resistant to many antibiotics. The development of alternative therapeutic compounds is the focus of extensive research, so novel nanoparticles (NPs) with activity against antibiotic-resistant bacteria should be developed. In this study, the antibacterial activity of quaternary ammonium polyethyleneimine (QA-PEI) NPs was evaluated against Streptococcus viridans, Stenotrophomonas maltophilia and Escherichia coli. To appraise the antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration and bactericidal assays were utilised with different concentrations (1.56-100 µg/ml) of QA-PEI NPs. Moreover, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and annexin V/propidium iodide toxicity assays were performed in cell cultures. MICs for S. maltophilia and E. coli isolates were 12.5 and 25 µg/ml, respectively, whereas the MIC for S. viridans was 100 µg/ml. Furthermore, the growth curve assays revealed that these QA-PEI NPs at a concentration of 12.5 µg/ml significantly inhibited bacterial growth for the bacterial isolates studied. On the other hand, QA-PEI NPs lacked significant toxicity for cells when used at concentrations up to 50 μg/ml for 48 h. The present findings reveal the potential therapeutic value of this QA-PEI NPs as alternative antibacterial agents for peritonitis, especially against Gram-negative bacteria.