13:30   BioMaterials
Chair: Nico Verdonschot
13:30
15 mins
SUPERCRITICAL ANTISOLVENT MICRONIZATION AS A TOOL FOR BIOMATERIALS PRODUCTION
Miguel Tavares Cardoso, J. Ruud van Ommen
Abstract: In the production of biomaterials covered with a layer of particles (e.g., for preventing inflammation or improving biocompatibility [1]), it is of crucial importance to have proper control over particle size and particle size distribution. Supercritical fluid technology is a powerful tool for the well-controlled production of particles with a desired size and size distribution. There are several micronization techniques based on or assisted by supercritical fluids, which are used according to the type of material to be micronized. These techniques are known as RESS (Rapid Expansion of Supercritical Solutions), GAS or SAS (Gas or Supercritical Fluid AntiSolvent), SEDS (Solution Enhanced Dispersion by Supercritical Fluids) or PGSS (Particles from Gas-Saturated Solutions or Suspensions). An extensive review on papers and patents, with a detailed explanation about these techniques was made by Jung and Perrut [2]. This work presents a general overview about these techniques and its potential in biomaterials production. This overview includes two successful examples of particle size reduction by supercritical antisolvent micronization; Minocycline Hydrochloride [3, 4] and beta-carotene [5]. Minocycline (Mcc) is a second-generation long-acting tetracycline that penetrates well into the central nervous system (CNS) via blood-brain barrier. In addition to its actions as antibiotic, Mcc has other biologic effects, such as affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism. Amorphous particles of minocycline ranging from 100 to 1000 nm (depending on the operating conditions) were obtained. Carotenoids are biological compounds responsible for the beneficial properties of fruits and vegetables in preventing human diseases, such as cardiovascular problems and cancer, among others chronic illnesses. The particle size obtained for beta-carotene ranged from 1 - 500 micron with mean particle diameters around 100 micron. REFERENCES [1] J.-X. Liu, D.-Z. Yang, F. Shi,, Y.-J. Cai,, “Sol-gel deposited TiO2 film on NiTi surgical alloy for biocompatibility improvement”, Thin Solid Films, Vol. 429 (1-2), pp. 225-230 (2003). [2] J. Jung, M. Perrut, “Particle design using supercritical fluids: Literature and patent survey”, J. of Supercrit. Fluids, Vol. 20, pp. 179-219, (2001). [3] M.A. Tavares Cardoso, G.A. Monteiro, J.P. Cardoso, T.J.V. Prazeres, J.M.F. Figueiredo, J.M.G. Martinho, J.M.S. Cabral and A.M.F. Palavra, “Supercritical micronization of minocycline hydrochloride”, J. of Supercritical Fluids, Vol. 44, pp. 238–244, (2008). [4] M.A. Tavares Cardoso, V. Geraldes, J.M.S. Cabral and A.M.F. Palavra, “Characterization of minocycline powder micronized by a supercritical antisolvent (SAS) process”, J. of Supercritical Fluids, Vol. 46, pp. 71–76, (2008). [5] M.A. Tavares Cardoso, S. Antunes, F. van Keulen, B.S. Ferreira, A. Geraldes, J.M.S. Cabral and A.M.F: Palava, “Supercritical antisolvent micronization of synthetic all-trans-β-carotene with tetrahydrofuran as solvent and carbon dioxide as antisolvent”, J. of Chem. Techn. & Biotechn., (2008), DOI: 10.1002/jctb.2027.
13:45
15 mins
MAGNETIC SENSING METHODS FOR MEDICAL APPLICATIONS
Bennie ten Haken
Abstract: Sensitive detection methods on magnetic nanoparticles in cells, tissue, and body liquids have a huge potential for new analysis methods both in medicine and biotechnology. Recently, dedicated magnetic nanoparticles have been increasingly developed and approved for various medical procedures, such as angiography and liver imaging in the case of MRI technique. Functionalised to increase their biocompatibility, these nanoparticles are then internalized by cells. The combination of nanotechnology and advanced magnetic sensing routes opens a realistic perspective of magnetic methods replacing nuclear and optical detection techniques in medicine and biotechnology. Within these prospects, we focus both on sensor development and on the detection and activation of new biocompatible magnetic nanoparticles in selected clinical applications. The first case study aims at the development of improved magnetic methods for the detection and characterisation of lymph nodes in relation to human colorectal carcinoma. Magnetic particles are detectable because of the small and linear magnetic response of the human body. This is analogue to the radioactive materials applied in nuclear imaging by positron emission tomography (PET), gamma cameras and gamma probes. In both cases the “contrast” material has a unique signature and the body is transparent for the detected signal. Whole-body imaging is reserved for large and expensive scanner systems as MRI and PET. During a surgical intervention a handheld device is routinely used to localise specifically marked tissue. In the nuclear variant this requires a handheld gamma probe and a radioactive marker. A magnetic equivalent for this is the handheld device developed by Endomagnetics, which is basically a very advanced metal detector. Magnetic sensing technology is continuously developed to become more sensitive and economical. Many magnetic sensors rely on semiconducting technology, e.g. magneto resistance sensors, (micro) hallprobes and spin-valve based devices. In the most demanding applications superconducting materials and sensors are used, in particular to obtain a lower noise level. In medical applications a SQUID (=Superconducting Quantum Interference Device) is used as a magnetic sensor to detect the ~10 fT strong magnetic fields from the brain, in a Magneto Encephalogram (MEG). The MEG technique is relatively complex because it requires a magnetically shielded room and a regular supply of liquid helium to cool the system. A more economical technology utilising a superconducting measurement system is recently developed in our group. This system will determine the tiny (~1 pT) magnetic response of the foetal heart with a SQUID sensor in a locally cooled system requiring no helium supply or magnetic shield.
14:00
15 mins
MAGNETIC DETECTION ON FERROMAGNETIC FE-FILLED CARBON NANOTUBES WITH A SQUID
Martin Sobik, Klingeler Ruediger, Hans Hilgenkamp, Bennie ten Haken
Abstract: Carbon nanotubes (CNTs) feature a large variety of outstanding mechanical, optical and electrical properties what confers to them an increasing interest. In the biomedical area the main applications are drugdelivery, hyperthermia and various imaging methods. Our work has been focused on the investigation of ferromagnetic properties linked to the presence of Fe inside multi-walled carbon nanotubes (MWNTs) synthesized by Liquid Source CVD. A CNTs detection procedure has been developed by means of Scanning (Superconducting Quantum Interference Device) Microscopy (SSM). Scanning Electron Microscopy (SEM) has also been performed in order to characterize the samples. For that purpose, lithography technique has been used on silicon oxide (SiO2) substrates to get a suitable (Nb wires) and special binary markers have also been uniformely distributed on the substrate in order to deposit and being able to locate more easily the Fe-filled MWNTs on with the SSM technique. Droplets of the sonicated suspension of Fe-filled CNTs in ethanol have been deposited onto that so structured silicon substrates. Single carbon nanotubes have been characterized at a significant magnification compared to SEM measurements and Fe filling inside the carbon nanotubes has been detected by means of SEM measurements. We estimate that detection of individual CNT’s is possible with a SQUID sensor up to 0.1 mm distance and intend to apply this in new biomedical applications.
14:15
15 mins
BIOCOMPATIBLE GOLD NANOPARTICLES AS CONTRAST AGENTS FOR LIGHT BASED IMAGING TECHNIQUES
Raja Gopal Rayavarapu, Wilma Petersen, Srirang Manohar, Ton van Leeuwen
Abstract: Gold nanoparticles are one of the most widely used classes of nanomaterials for many biomedical applications. There are numerous methods known for the synthesis of gold nanoparticles, the ability to control the size, shape and monodispersity of gold nanoparticles is a critical and challenging parameter. When light interacts with gold nanoparticles, plasmons are excited which result in sharp and narrow absorption peaks.One dimensional nanostructures such as gold nanorods, have two plasmon peaks; the transverse and the longitudinal plasmon peaks. By changing the length and width of the nanorod, the longitudinal plasmon peak can be red-shifted towards the near-infrared region (NIR) where light penetration in tissue is high which is useful for in vivo imaging applications. We have synthesized gold nanorods (AuNR628 nm and AuNR773 nm) which have respectively longitudinal plasmon peaks at 628 nm and 773 nm. Gold nanorods were synthesized using wet-chemical seed-mediated methods. During synthesis, cetyltrimethylammoniumbromide (CTAB) acts as a stabilizing agent and binds selectively to certain facets on seed and thus resulting in one-dimensional growth. The as-prepared gold nanorods are toxic to cells due to the presence of CTAB bilayer on the surface of gold nanorod. To make gold nanorods biocompatible, we have coated gold nanorods using polymers such as PEG and PSS which are neutral and negatively charged respectively. The PEGylation of gold nanorods displaces CTAB from the surface whereas PSS binds electro-statically to the positively charged CTAB bilayer and shields over the surface of nanorod. We have studied cytotoxicity on different cell lines such as adherent (SKBR3, CHO, and C2C12) and suspension (HL60) cell lines. We quantified the toxicity of gold nanorods at different range of picoMolar (pM) concentrations using an MTS assay. The as-prepared CTAB gold nanorods and filtered gold nanorods showed 100% cell death in all cell lines studied. Overall, the PEG-coated gold nanorods showed increased cell viability even at very high concentrations. The PSS coated nanorods also improved cell viability to an extent but not in the manner of PEGylated gold nanorods. Characterization, size estimation and surface charge were performed using electron microscopies, optical spectroscopy and zeta potential measurements. We present these detailed toxicity results of gold nanorods on different cell lines for use of these gold nanorods for in vivo biomedical applications.
14:30
15 mins
SUSTAINED RELEASE OF DEXAMETHASONE FROM PLGA MICROSPHERES: INFLUENCE OF POLYMER ATTRIBUTES AND SPHERE MORPHOLOGY
Gwen Dawes, Lidy Fratila-Apachitei, Iulian Apachitei, Jurek Duszczyk
Abstract: During 2007, there were more than 150,000 patients requiring total or partial joint arthroplasty in the United Kingdom alone. At the same time, 13,000 patients required revision surgery, many of these due to septic or aseptic implant loosening. From the materials viewpoint, fixation of the implant to the bone is achieved by the use of bone cement or by microtexturing implant surfaces so that novel bone can grow into the implant itself. Current drug encapsulation technology allows for the production of drug-eluting devices that can enhance cementless implant fixation by delivering specific bioactives to the implant site over the required period. In this study, experiments have been performed to encapsulate dexamethasone, a powerful anti-inflammatory and bone mineralization factor, into poly (lactide-co-glycolide) (PLGA) microspheres using an emulsion/solvent evaporation technique. The resulting microspheres were analysed for morphology and size distribution by scanning electron microscopy. Drug release profiles over thirty days in simulated body fluid were obtained by the use of high performance liquid chromatography (HPLC). It was shown that the release of dexamethasone may be sustained for a longer time by increasing the molecular weight of the polymer used (12,000Da to 57,500Da) or increasing the monomeric ratios (50% lactide to 85% lactide). Increasing the sphere size (1μm to 20 μm) caused the concentration of dexamethasone loaded into each microsphere to decrease, but the release profile became more linear over 30 days. Future works will involve investigating the release of dexamethasone from poly(lactide-co-glycolide) microspheres immobilised on the surface of oxidised titanium.