Synthesis of Precision Gold Nanoparticles Using Turkevich Method.

Gold nanoparticles (AuNPs) exhibit unique size-dependent physiochemical properties that make them attractive for a wide range of applications. However, the large-scale availability of precision AuNPs has been minimal. Not only must the required nanoparticles be of precise size and morphology, but they must also be of exceedingly narrow size distribution to yield accurate and reliable performance. The present study aims to synthesize precision AuNPs and to assess the advantages and limitations of the Turkevich method-one of the common chemical synthesis technique. Colloidal AuNPs from 15 nm to 50 nm in diameter were synthesized using the Turkevich method. The effect of the molar ratio of the reagent mixture (trisodium citrate to gold chloride), the scaled-up batch size, the initial gold chloride concentration, and the reaction temperature was studied. The morphology, optical property, surface chemistry, and chemical composition of AuNPs were thoroughly characterized. It was determined that the as-synthesized AuNPs between 15 nm and 30 nm exhibit well-defined size and shape, and narrow size distribution (PDI < 0.20). However, the AuNPs became more polydispersed and less spherical in shape as the particle size increased.

Particle assisted removal of microbes from surfaces.

Increased reliance on kill based approaches for disinfection raises concerns of antimicrobial resistance development and has significantly elevated the need for alternate approaches for skin and substrate disinfection. This study focuses on reducing harmful microbes from substrates primarily via removal and to a lesser extent by kill. HYPOTHESIS: Functional micro-particles designed to adhere to microbes, with a force greater than the force of microbial adhesion to the substrate, would result in enhanced removal-based disinfection of substrates when subject to an external force. EXPERIMENTS: Silica particles were functionalized with a cationic polymer to bind strongly with bacteria via Coulombic interactions. Disinfection efficacies of substrates with functional particles and control groups were evaluated under conditions relevant for handwashing. FINDINGS: Functionalized silica micro-particles result in ∼4 log reduction of E. coli from an artificial skin substrate in 30 s as compared to a maximum of 1.5 log reduction with control particles. Bacterial viability assays indicate a mechanism of action driven by enhanced removal of bacteria with minimal kill. Particle number density, size and suspension velocity along with strong particle - bacteria interactions have been found to be the primary factors responsible for the enhanced bacterial removal from surfaces.

Mussel-inspired 3D fiber scaffolds for heart-on-a-chip toxicity studies of engineered nanomaterials.

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pathological consequences of ENM exposure represents an important challenge, requiring model systems that can provide mechanistic insights across different levels of ENM-based toxicity. To achieve this, we developed a mussel-inspired 3D microphysiological system (MPS) to measure cardiac contractility in the presence of ENMs. While multiple cardiac MPS have been reported as alternatives to in vivo testing, most systems only partially recapitulate the native extracellular matrix (ECM) structure. Here, we show how adhesive and aligned polydopamine (PDA)/polycaprolactone (PCL) nanofiber can be used to emulate the 3D native ECM environment of the myocardium. Such nanofiber scaffolds can support the formation of anisotropic and contractile muscular tissues. By integrating these fibers in a cardiac MPS, we assessed the effects of TiO2 and Ag nanoparticles on the contractile function of cardiac tissues. We found that these ENMs decrease the contractile function of cardiac tissues through structural damage to tissue architecture. Furthermore, the MPS with embedded sensors herein presents a way to non-invasively monitor the effects of ENM on cardiac tissue contractility at different time points. These results demonstrate the utility of our MPS as an analytical platform for understanding the functional impacts of ENMs while providing a biomimetic microenvironment to in vitro cardiac tissue samples. Graphical Abstract Heart-on-a-chip integrated with mussel-inspired fiber scaffolds for a high-throughput toxicological assessment of engineered nanomaterials.

EphA2 targeted intratumoral therapy for non-small cell lung cancer using albumin mesospheres.

Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer mortality and the prognosis of patients with advanced or metastatic NSCLC is poor. Despite significant advances in diagnosis and treatment, little improvement has been seen in NSCLC mortality. Recently, Intratumoral Chemotherapy, a direct local delivery of chemotherapeutic drugs, has shown promise in clinical studies. However, toxicity and high dosage of chemotherapeutic agents used for treatment are a limitation. Moreover, these drugs damage indiscriminately, cancerous as well as normal tissues. Thus, a novel therapeutic strategy that targets only malignant tissue sparing normal tissue becomes an urgent issue. Ephrin receptor-A2 (EphA2), a new biomarker, is over-expressed in NSCLC, but not on normal epithelial cells. Receptor EphA2 is a cell surface protein, which upon binding to its ligand EphrinA1 undergo phosphorylation and degradation which attenuates NSCLC growth. Targeting the tumor, sparing the normal tissue and enhancing the therapeutic effects of ligand proteins are the goal of this project. Thus a novel method, intratumoral EphA2 targeted therapy, has been developed to target the oncogenic receptors on tumor tissue by using albumin mesosphere (AMS) conjugated ephrinA1 in mice bearing NSCLC tumors.

Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer.

MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1-LNP) and let-7a miR encapsulated LNP (miR-LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR-ephrin-A1-LNP) was determined on MPM and NSCLC tumor growth in vitro. miR-ephrin-A1-LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR-ephrin-A1-LNP treatment. Furthermore, the miR-ephrin-A1-LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR-ephrin-A1-LNP complex is an effective carrier for the targeted delivery of small RNA molecules to lung cancer cells. This could be a potential therapeutic approach against tumors overexpressing the EphA2 receptor.

Fe Doped CdTeS Magnetic Quantum Dots for Bioimaging.

A facile synthesis of 3-6 nm, water dispersible, near-infrared (NIR) emitting, quantum dots (QDs) magnetically doped with Fe is presented. Doping of alloyed CdTeS nanocrystals with Fe was achieved in situ using a simple hydrothermal method. The magnetic quantum dots (MQDs) were capped with NAcetyl-Cysteine (NAC) ligands, containing thiol and carboxylic acid functional groups to provide stable aqueous dispersion. The optical and magnetic properties of the Fe doped MQDs were characterized using several techniques. The synthesized MQDs are tuned to emit in the Vis-NIR (530-738 nm) wavelength regime and have high quantum yields (67.5-10%). NIR emitting (738 nm) MQDs having 5.6 atomic% Fe content exhibited saturation magnetization of 85 emu/gm[Fe] at room temperature. Proton transverse relaxivity of the Fe doped MQDs (738 nm) at 4.7 T was determined to be 3.6 mM-1s-1. The functional evaluation of NIR MQDs has been demonstrated using phantom and in vitro studies. These water dispersible, NIR emitting and MR contrast producing Fe doped CdTeS MQDs, in unagglomerated form, have the potential to act as multimodal contrast agents for tracking live cells.

Gadolinium-doped silica nanoparticles encapsulating indocyanine green for near infrared and magnetic resonance imaging.

Clinical applications of the indocyanine green (ICG) dye, the only near infrared (NIR) imaging dye approved by the Food and Drug Administration (FDA) in the USA, are limited due to rapid protein binding, fast clearance, and instability in physiologically relevant conditions. Encapsulating ICG in silica particles can enhance its photostability, minimize photobleaching, increase the signal-to-noise (S/N) ratio and enable in vivo studies. Furthermore, a combined magnetic resonance (MR) and NIR imaging particulate can integrate the advantage of high-resolution 3D anatomical imaging with high-sensitivity deep-tissue in-vivo fluorescent imaging. In this report, a novel synthesis technique that can achieve these goals is presented. A reverse-microemulsion-based synthesis protocol is employed to produce 25 nm ICG-doped silica nanoparticles (NPs). The encapsulation of ICG is achieved by manipulating coulombic attractions with bivalent ions and aminated silanes and carrying out silica synthesis in salt-catalyzed, mildly basic pH conditions using dioctyl sulfosuccinate (AOT)/heptane/water microemulsion system. Furthermore, paramagnetic properties are imparted by chelating paramagnetic Gd to the ICG-doped silica NPs. Aqueous ICG-dye-doped silica NPs show increased photostability (over a week) and minimal photobleaching as compared to the dye alone. The MR and optical imaging capabilities of these particles are demonstrated through phantom, in vitro and in vivo experiments. The described particles have the potential to act as theranostic agents by combining photodynamic therapy through the absorption of NIR irradiated light.

Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy.

BACKGROUND: Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology. METHODS: We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallo-naphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model. RESULTS: The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (>110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis. CONCLUSION: MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.

Influence of Suwannee River humic acid on particle properties and toxicity of silver nanoparticles.

Adsorption of natural organic matter (NOM) on nanoparticles can have dramatic impacts on particle dispersion resulting in altered fate and transport as well as bioavailability and toxicity. In this study, the adsorption of Suwannee River humic acid (SRHA) on silver nanoparticles (nano-Ag) was determined and showed a Langmuir adsorption at pH 7 with an adsorption maximum of 28.6 mg g(-1) nano-Ag. It was also revealed that addition of <10 mg L(-1) total organic carbon (TOC) increased the total Ag content suspended in the aquatic system, likely due to increased dispersion. Total silver content decreased with concentrations of NOM greater than 10mg TOCL(-1) indicating an increase in nanoparticle agglomeration and settling above this concentration. However, SRHA did not have any significant effect on the equilibrium concentration of ionic Ag dissolved in solution. Exposure of Daphnia to nano-Ag particles (50 µg L(-1) and pH 7) produced a linear decrease in toxicity with increasing NOM. These results clearly indicate the importance of water chemistry on the fate and toxicity of nanoparticulates.

Fractionated photothermal antitumor therapy with multidye nanoparticles.

PURPOSE: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR) light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs) after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs) for fractionated photothermal antitumor therapy. METHODS: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice. RESULTS: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm) retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026) in experimental tumor-bearing mice compared to control treated tumor-bearing mice. CONCLUSION: Fractionated photothermal therapy for cancer represents a new therapeutic paradigm enabled by the application of novel functional nanomaterials. MDT-NPs may advance clinical treatment of cancer by enabling fractionated real-time image guided photothermal therapy.

Fluorescent and paramagnetic chitosan nanoparticles that exhibit high magnetic resonance relaxivity: synthesis, characterization and in vitro studies.

We report water-in-oil (W/O) microemulsion synthesis of fluorescently bright and paramagnetically strong bimodal chitosan nanoparticles (BCNPs). The W/O microemulsion system provides a confined environment for producing monodispersed BCNPs. Average particle size as estimated by the Transmission Electron Microscopy was 28 nm. The water to surfactant molar ratio of 22 produced small size fairly monodispersed BCNPs. Fluorescein isothiocyanate (FITC, a fluorescent dye) and Gd-DOTA (a paramagnetic Gd ion chelating agent) were covalently attached to chitosan polymer backbone prior to BCNP synthesis. The purpose of the covalent attachment of fluorescent and paramagnetic labels to chitosan is to prevent leakage of these labels from the BCNPs. The BCNPs were cross-linked with tartaric acid using water-soluble carbodiimide coupling chemistry in order to maintain particulate integrity. Zeta potential value of +27.6 mV confirmed positive surface charge of cross-linked BCNPs. Fluorescence excitation and emission spectra of BCNPs were similar to that of bare FITC spectra, showing characteristic 520 nm emission at the 490 excitation. Paramagnetic gadolinium ion (Gd3+) concentration in the BCNPs was determined by inductively coupled plasma (ICP) emission spectroscopy. The longitudinal (T1) and transverse (T2) proton relaxation times were determined as a function of Gd3+ concentration in the BCNPs at 4.7 Tesla. Proton relaxivity (R1 value) of BCNPs was calculated to be 41.1 mM Gd(-1)s(-1). The reported R1 value of Gd-DOTA chelates is however 5.8 mM Gd(-1)s(-1). High proton relaxivity of BCNPs is attributed to hydrated chitosan environment around Gd chelates which additionally contributed to overall water exchange process. To demonstrate in vitro bioimaging capability, J774 macrophage cells were incubated with BCNPs. Confocal images clearly showed BCNP uptake by J774 cells. Internalization of BCNPs was confirmed by co-labeling J774 cells with a red-emitting membrane dye. BCNP green emission was mostly observed from middle of cells and within the red-emitting membrane boundary.

Classification of cancer cell death with spectral dimensionality reduction and generalized eigenvalues.

OBJECTIVE: Accurate cell death discrimination is a time consuming and expensive process that can only be performed in biological laboratories. Nevertheless, it is very useful and arises in many biological and medical applications. METHODS AND MATERIAL: Raman spectra are collected for 84 samples of A549 cell line (human lung cancer epithelia cells) that has been exposed to toxins to simulate the necrotic and apoptotic death. The proposed data mining approach for the multiclass cell death discrimination problem uses a multiclass regularized generalized eigenvalue algorithm for classification (multiReGEC), together with a dimensionality reduction algorithm based on spectral clustering. RESULTS: The proposed algorithmic scheme can classify A549 lung cancer cells from three different classes (apoptotic death, necrotic death and control cells) with 97.78%± 0.047 accuracy versus 92.22 ± 0.095 without the proposed feature selection preprocessing. The spectrum areas depicted by the algorithm corresponds to the 〉C O bond from the lipids and the lipid bilayer. This chemical structure undergoes different change of state based on cell death type. Further evidence of the validity of the technique is obtained through the successful classification of 7 cell spectra that undergo hyperthermic treatment. CONCLUSIONS: In this study we propose a fast and automated way of processing Raman spectra for cell death discrimination, using a feature selection algorithm that not only enhances the classification accuracy, but also gives more insight in the undergoing cell death process.

The promise of nanotechnology for solving clinical problems in breast cancer.

Approaches for breast cancer treatment are invasive, disfiguring, have significant side-effects, and are not always curative. Nanotechnology is an emerging area which is focused on engineering of materials <100 × 10(-9) m. There is significant promise for advancing nanotechnology to improve breast cancer diagnosis and treatment including non-invasive therapy, monitoring response to therapy, advanced imaging, treatment of metastatic disease, and improved nodal staging. Current approaches and important future directions are discussed.

Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives.

Nanoparticle-based contrast agents are quickly becoming valuable and potentially transformative tools for enhancing medical diagnostics for a wide range of in-vivo imaging modalities. Compared with conventional molecular-scale contrast agents, nanoparticles (NPs) promise improved abilities for in-vivo detection and potentially enhanced targeting efficiencies through longer engineered circulation times, designed clearance pathways, and multimeric binding capacities. However, NP contrast agents are not without issues. Difficulties in minimizing batch-to-batch variations and problems with identifying and characterizing key physicochemical properties that define the in-vivo fate and transport of NPs are significant barriers to the introduction of new NP materials as clinical contrast agents. This manuscript reviews the development and application of nanoparticles and their future potential to advance current and emerging clinical bioimaging techniques. A focus is placed on the application of solid, phase-separated materials, for example metals and metal oxides, and their specific application as contrast agents for in-vivo near-infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound (US), and photoacoustic imaging (PAI). Clinical and preclinical applications of NPs are identified for a broad spectrum of imaging applications, with commentaries on the future promise of these materials. Emerging technologies, for example multifunctional and theranostic NPs, and their potential for clinical advances are also discussed.

Tailoring silica nanotribology for CMP slurry optimization: Ca(2+) cation competition in C(12)TAB mediated lubrication.

Self-assembled surfactant structures at the solid/liquid interface have been shown to act as nanoparticulate dispersants and are capable of providing a highly effective, self-healing boundary lubrication layer in aqueous environments. However, in some cases in particular, chemical mechanical planarization (CMP) applications the lubrication imparted by self-assembled surfactant dispersants can be too strong, resulting in undesirably low levels of wear or friction disabling material removal. In the present investigation, the influence of calcium cation (Ca(2+)) addition on dodecyl trimethylammonium bromide (C(12)TAB) mediated lubrication of silica surfaces is examined via normal and lateral atomic force microscopy (AFM/LFM), benchtop polishing experiments and surface adsorption characterization methods. It is demonstrated that the introduction of competitively adsorbing cations that modulate the surfactant headgroup surface affinity can be used to tune friction and wear without compromising dispersion stability. These self-healing, reversible, and tunable tribological systems are expected to lead to the development of smart surfactant-based aqueous lubrication schemes, which include designer polishing slurries and devices that take advantage of pressure-gated friction response phenomena.

What is cancer nanotechnology?

Cancer nanotechnology has the potential to dramatically improve current approaches to cancer detection, diagnosis, imaging, and therapy while reducing toxicity associated with traditional cancer therapy (1, 2). In this overview, we will define cancer nanotechnology, consider issues related to application of nanotechnology for cancer imaging and therapy, and broadly consider implications for continued development in nanotechnology for the future of clinical cancer care. These considerations will place in perspective the methodological approaches in cancer nanotechnology and subject reviews outlined in this volume.

Nanoparticle characterization for cancer nanotechnology and other biological applications.

Nanotechnology is actively being used to develop promising diagnostics and therapeutics tools for the treatment of cancer and many other diseases. The unique properties of nanomaterials offer an exciting frontier of possibilities for biomedical researchers and scientists. Because existing knowledge of macroscopic materials does not always allow for adequate prediction of the characteristics and behaviors of nanoscale materials in controlled environments, much less in biological systems, careful nanoparticle characterization should accompany biomedical applications of these materials. Informed correlations between adequately characterized nanomaterial properties and reliable biological endpoints are essential for guiding present and future researchers toward clinical nanotechnology-based solutions for cancer. Biological environments are notoriously dynamic; hence, nanoparticulate interactions within these environments will likely be comparatively diverse. For this reason, we recommend that an interactive and systematic approach to material characterization be taken when attempting to elucidate or measure biological interactions with nanoscale materials. We intend for this chapter to be a practical guide that could be used by researchers to identify key nanomaterial characteristics that require measurement for their systems and the appropriate techniques to perform those measurements. Each section includes a basic overview of each measurement and notes on how to address some of the common difficulties associated with nanomaterial characterization.

Multimodal nanoparticulate bioimaging contrast agents.

A wide variety of bioimaging techniques (e.g., ultrasound, computed X-ray tomography, magnetic resonance imaging (MRI), and positron emission tomography) are commonly employed for clinical diagnostics and scientific research. While all of these methods use a characteristic "energy-matter" interaction to provide specific details about biological processes, each modality differs from another in terms of spatial and temporal resolution, anatomical and molecular details, imaging depth, as well as the desirable material properties of contrast agents needed for augmented imaging. On many occasions, it is advantageous to apply multiple complimentary imaging modalities for faster and more accurate prognosis. Since most imaging modalities employ exogenous contrast agents to improve the signal-to-noise ratio, the development and use of multimodal contrast agents is considered to be highly advantageous for obtaining improved imagery from sought-after imaging modalities. Multimodal contrast agents offer improvements in patient care, and at the same time can reduce costs and enhance safety by limiting the number of contrast agent administrations required for imaging purposes. Herein, we describe the synthesis and characterization of nanoparticulate-based multimodal contrast agent for noninvasive bioimaging using MRI, optical, and photoacoustic tomography (PAT)-imaging modalities. The synthesis of these agents is described using microemulsions, which enable facile integration of the desired diversity of contrast agents and material components into a single entity.

Cell death discrimination with Raman spectroscopy and support vector machines.

In the present study, Raman spectroscopy is employed to assess the potential toxicity of chemical substances. Having several advantages compared to other traditional methods, Raman spectroscopy is an ideal solution for investigating cells in their natural environment. In the present work, we combine the power of spectral resolution of Raman with one of the most widely used machine learning techniques. Support vector machines (SVMs) are used in the context of classification on a well established database. The database is constructed on three different classes: healthy cells, Triton X-100 (necrotic death), and etoposide (apoptotic death). SVM classifiers successfully assess the potential effect of the test toxins (Triton X-100, etoposide). The cells that are exposed to heat (45 degrees C) are tested using the classification rules obtained. It is shown that the heat effect results in apoptotic death, which is in agreement with existing literature.

Effect of chain length on binding of fatty acids to Pluronics in microemulsions.

We investigated the effect of fatty acid chain length on the binding capacity of drug and fatty acid to Pluronic F127-based microemulsions. This was accomplished by using turbidity experiments. Pluronic-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated Amitriptyline, an antidepressant drug. Sodium salts of C(8), C(10), or C(12) fatty acid were used in preparation of the microemulsion and the corresponding binding capacities were observed. It has been previously determined that, for microemulsions prepared with sodium caprylate (C(8) fatty acid soap), a maximum of 11 fatty acid molecules bind to the microemulsion per 1 molecule of Pluronic F127 and a maximum of 12 molecules of Amitriptyline bind per molecule of F127. We have found that with increasing the chain length of the fatty acid salt component of the microemulsion, the binding capacity of both the fatty acid and the Amitriptyline to the microemulsion decreases. For sodium salts of C(8), C(10) and C(12) fatty acids, respectively, a maximum of approximately 11, 8.4 and 8.3 molecules of fatty acid molecules bind to 1 Pluronic F127 molecule. We propose that this is due to the decreasing number of free monomers with increasing chain length. As chain length increases, the critical micelle concentration (cmc) decreases, thus leading to fewer monomers. Pluronics are symmetric tri-block copolymers consisting of propylene oxide (PO) and ethylene oxide (EO). The polypropylene oxide block, PPO is sandwiched between two polyethylene oxide (PEO) blocks. The PEO blocks are hydrophilic while PPO is hydrophobic portion in the Pluronic molecule. Due to this structure, we propose that the fatty acid molecules that are in monomeric form most effectively diffuse between the PEO "tails" and bind to the hydrophobic PPO groups.