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Biomedical subjects

P N Prasad

Publications and source records attributed to P N Prasad.

13 recordsLinked to original sources

Elasticity-mediated self-organization and colloidal interactions of solid spheres with tangential anchoring in a nematic liquid crystal.

Using laser tweezers, we study colloidal interactions of solid microspheres in the nematic bulk caused by elastic distortions around the particles with tangential surface anchoring. The interactions overcome the Brownian motion when the interparticle separation r-->p is less than 3 particle diameters. The particles attract when the angle theta between r-->p and the uniform far-field director n0 is between 0 degrees and approximately 70 degrees and repel when 75 degrees <or approximately theta<or=90 degrees. The particles aggregate in chains directed at approximately 30 degrees to n0 and, at higher concentrations, form complex kinetically trapped structures.

Colloids↗

Chemically fabricated magnetic quantum dots of InP:Mn.

Quantum dots of InP:Mn are chemically prepared by following hot colloidal nanochemistry with starting precursors that obviate the need for external surfactant. These quantum dots are uniform spheres with 3-nm diameters; they are crystalline, photoluminescent, and magnetic. The crystallographic and optical properties are similar to those of undoped InP nanocrystallites, while the magnetism is consistent with the ferromagnetic response observed in a class of diluted magnetic semiconductors. Because of the ultrafine sizes, the sample shows superparamagnetic behavior, whereas ferromagnetic hysteresis loops are clearly seen below the blocking temperature. Structural characterization and analysis confirm that the magnetism in these quantum dots is not due to segregated binary MnP or MnO phases and that they truly represent a homogeneous dilute magnetic semiconductor.

Electron Spin Resonance Spectroscopy↗

Gold nanoshells on polystyrene cores for control of surface plasmon resonance.

A method is presented for synthesizing core-shell structures consisting of monodisperse polystyrene latex nanospheres as cores and gold nanoparticles as shells. Use of polystyrene spheres as the core in these structures is advantageous because they are readily available commercially in a wide range of sizes, and with dyes or other molecules doped into them. Gold nanoparticles, ranging in size from 1 to 20 nm, are prepared by reduction of a gold precursor with sodium citrate or tetrakis(hydroxymethyl)phosphonium chloride (THPC). Carboxylate-terminated polystyrene spheres are functionalized with 2-aminoethanethiol hydrochloride (AET), which forms a peptide bond with carboxylic acid groups on their surface, resulting in a thiol-terminated surface. Gold nanoparticles then bind to the thiol groups to provide up to about 50% coverage of the surface. These nanoparticles serve as seeds for growth of a continuous gold shell by reduction of additional gold precursor. The shell thickness and roughness can be controlled by the size of the nanoparticle seeds as well as by the process of their growth into a continuous shell. By variation of the relative sizes of the latex core and the thickness of the gold overlayer, the plasmon resonance of the nanoshell can be tuned to specific wavelengths across the visible and infrared range of the electromagnetic spectrum, for applications ranging from the construction of photonic crystals to biophotonics. The position and width of the plasmon resonance extinction peak are well-predicted by extended Mie scattering theory.

Journal Article↗

Polycarboxylic acid nanoparticles for ophthalmic drug delivery: an ex vivo evaluation with human cornea.

In ophthalmic drug delivery, a major problem is retaining an adequate concentration of a therapeutic agent in the pre-corneal area. Polycarboxylic acid carriers such as polyacrylic acid and polyitaconic acid in sub-colloidal, nanoparticulate hydrogel form have a strong potential for sustained release of a drug in ocular delivery. Formulations have been prepared of brimonidine loaded in polycarboxylic (polyacrylic and polyitaconic) acid nanoparticles for potential ophthalmic delivery. These particles were prepared by a reverse micro-emulsion polymerization technique with sizes in the range of 50 nm. The loading efficiencies of the drug brimonidine in the particles were shown to be between 80-85% for polyacrylic acid nanoparticles and between 65-70% for polyitaconic nanoparticles. The loading efficiency was also found to be pH dependent. In a preliminary biocompatibility test, human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability, whereas polyitaconic acid nanoparticles were found to be toxic. Two-photon laser scanning microscopic studies of the fluorescently labelled polyacrylic acid nanoparticles and human cornea shows that they are adhesive on the corneal surface. The polyacrylic acid nanoparticles demonstrated a controlled release of the opthalmological drug (Brimonidine) through the human cornea as compared to that of the commercial formulation, Alphagan.

Acrylates↗

Measurement of optical trapping forces by use of the two-photon-excited fluorescence of microspheres.

A novel technique for the calibration of laser trapping systems that utilizes two-photon-excited fluorescence of commercial dye-stained microspheres has been demonstrated. The trapping forces as well as the trapping efficiency have been measured for various liquid environments and trapping depths. The trapping efficiency in water was found to decrease with an increase of trapping depths because of the enlargement of the trapping beam waist caused by aberrations of the optical system.

Fluorescence↗

Studies on the mechanism of action of a targeted chemotherapeutic drug in living cancer cells by two photon laser scanning microspectrofluorometry.

In this study, we present a spectroscopic study of the entry pattern of a chemotherapeutic drug (AN-152) and its carrier hormone ([D-Lys(6)]LH-RH) into living cancer cells, with the help of our two-photon probes and a home-built localized microspectrofluorometer coupled with two photon laser scanning microscope (TPLSM). Due to the inherent localization ability of TPLSM, we were able to identify the drug and carrier location in different compartments of the cancer cells in vitro. The apparent doxorubicin-assisted nucleic accumulation of AN-152 suggests a possible nuclear action of the drug on cell proliferation.

Antineoplastic Agents↗

Regulation of targeted chemotherapy with cytotoxic lutenizing hormone-releasing hormone analogue by epidermal growth factor.

Targeting chemotherapy selectively to cancers can reduce the toxic side effects. AN-152, a conjugate of doxorubicin and [D-Lys6]-luteinizing hormone-releasing hormone (LH-RH), is more potent against LH-RH receptor-bearing cancers and produces less peripheral toxicity than doxorubicin. Many cancers, e.g., 50% of breast cancers, but few normal tissues express these receptors, providing a selective target for this cytotoxic conjugate. In this study, the effectiveness of AN-152 was heightened by receptor up-regulation. The cytotoxic effect of AN-152 can be regulated by the number of active LH-RH receptors on cancer cells. LH-RH receptor-positive (MCF-7) and -negative (UCI-107) cancer cells were treated with epidermal growth factor (EGF) or the somatostatin analogue, RC-160. EGF and RC-160 have been shown previously to regulate LH-RH receptors through phosphorylation. The effect of receptor regulation, by hormone exposure, on the cytotoxicity of AN-152 and doxorubicin and on the cellular uptake of AN-152, [D-Lys6]LH-RH, or doxorubicin was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and by two-photon laser scanning microscopy. The results demonstrated that the cellular entry of the conjugate was: (a) specific for cancers with LH-RH receptors; (b) up-regulated by EGF; (c) down-regulated by RC-160; and (d) the cytotoxicity of the AN-152 paralleled the efficiency of entry. This study illustrates the potential use of receptor regulation for increasing the efficacy of chemotherapeutic approaches that are directed to cell surface receptors.

Antineoplastic Agents↗

A chemically labeled cytotoxic agent: two-photon fluorophore for optical tracking of cellular pathway in chemotherapy.

Chemotherapy is commonly used in the treatment of cancers. However, the mechanism of action of many of these agents is not well understood. We present the synthesis of a two-photon fluorophore (C625) and its biological application when chemically linked to a chemotherapeutic agent (AN-152). By using two-photon laser-scanning microscopy, the drug:fluorophore conjugate can be observed directly as it interacts with receptor-positive cell lines. The results of this project visually show the receptor-mediated entry of AN-152 into the cell cytoplasm and subsequently into the nucleus. These observations will allow for better understanding of the drug's therapeutic mechanism, which is a subject of ongoing research aimed at improving present methods for cancer therapy.

Antineoplastic Agents↗

Two-photon photodynamic therapy.

OBJECTIVE: We demonstrate the use of infrared excitation in conjunction with an efficient two-photon absorbing dye and a photosensitizer in photodynamic therapy. SUMMARY BACKGROUND DATA: An efficient two-photon absorbing dye is excited by short infrared (800 nm) laser pulses, which transfer its energy to the photosensitizer and the photosensitizer, in turn, generates the singlet oxygen. METHODS: A new approach to photodynamic cancer therapy based on the strong two-photon absorption of certain newly developed organic molecules. Near infrared pulsed laser light efficiently excites these molecules which, in turn, transfer the energy to the photosensitizer used in photodynamic therapy. RESULTS: A newly synthesized two-photon absorbing dye 4-[N-(2-hydroxyethyl)-N-(methyl) amino phenyl]-4'-(6-hydroxyhexyl sulfonyl)stilbene (APSS), which exhibits a strong two-photon absorption at 800 nm, and upconverted fluorescence at 520 nm, in solution in the presence of a photosensitizer was found to generate singlet oxygen under infrared excitation (800 nm). The generation of singlet oxygen in a reaction system containing two-photon absorbing dye and photosensitizer under infrared excitation has been chemically detected by using ADPA (9,10-anthracenedipropionic acid) as singlet oxygen detector. CONCLUSIONS: The efficient two-photon absorption of certain chromophores can be used to extend photodynamic therapy to the near infrared spectral region. Whereas the photosensitizer itself may not exhibit two-photon absorption, it could be used in conjunction with one of these new chromophores. The chromophores can act as "photon harvesters" whereby they absorb two photons of near infrared light and transfer the energy to the photosensitizer, which can generate singlet oxygen in the presence of atmospheric oxygen.

Absorption↗

Three-dimensional laser scanning two-photon fluorescence confocal microscopy of polymer materials using a new, efficient upconverting fluorophore.

Three-dimensional confocal imaging of polymer samples was achieved by the use of two-photon excited fluorescence in both positive and negative contrast modes. The fluorophore was a new and highly efficient two-photon induced upconverter, resulting in improved signal strength at low pumping power. Because of the relatively long wavelength of the excitation source (798 nm from a mode-locked Ti:Sapphire laser), this technique shows a larger penetration depth into the samples than provided by conventional single-photon fluorescence confocal microscopy. Single-photon and two-photon images of the same area of each sample show significant differences. The results suggest the possibility of using two-photon confocal microscopy, in conjunction with highly efficient fluorophores, as a tool to study the surface, interface, and fracture in material science applications.

Fluorescent Dyes↗

Laser Raman investigation of drug-polymer conjugates: sulfathiazole-povidone coprecipitates.

Laser Raman spectroscopy is used for the investigation of the drug-polymer conjugates, sulfathiazole-povidone. Specifically, Raman spectra, both in the lattice vibration and the intramolecular vibration regions, are used to characterize various polymoprhic forms of sulfathiazole. It is found that sulfathiazole exists in two unsolvated forms, untreated sulfathiazole and another form grown from propanol. The crystals grown from ethanol include varying amounts of ethanol depending on the growth condition. The nature of the povidone-sulfathiazole coprecipitates of various compositions are studied. We find no evidence of any new polymorphic form of sulfathiazole in these coprecipitates. The coprecipitates are found to consist of one of the unsolvated forms of sulfathiazole.

Chemistry, Pharmaceutical↗

Laser Raman investigation of pharmaceutical solids: griseofulvin and its solvates.

Laser Raman spectroscopy is convenient for characterizing griseofulvin solvates and investigating solute-solvent interactions and desolvation. The spectra of both lattice and intramolecular vibrations were monitored. A new solvate of griseofulvin wih bromoform was characterized by Raman spectroscopy. A temperature-dependence study of the solvates of griseofulvin with chloroform, and benzene revealed no phase transformation or chemical change. In the benzene solvate, only weak Van der Waals interactions existed between the solute and solvent. However, in solvates with chloroform and bromoform, a weak hydrogen binding existed between the proton of the solvent and the C = O group of the benzofuran ring in griseofulvin. Examination of desolvation in these solvates revealed that the crystal did not go through any intermediate structure during desolvation. As the solvent molecule escaped, the lattice reverted to the structure of unsolvated griseofulvin.

Chemical Phenomena↗

Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery.

In ocular drug delivery, a major problem is providing an adequate concentration of a therapeutic agent in the precorneal area. Mucoadhesive carriers such as polyacrylic acid in sub-colloidal, nanoparticulate form, have a strong potential for ophthalmic drug delivery. A formulation of brimonidine loaded in polyacrylic acid nanoparticles has been prepared for potential delivery in ophthalmic therapy. The particles were prepared by a reverse microemulsion polymerization technique and their sizes were in the range of 50 nm. In a preliminary biocompatibility test, Caco-2 cells (human primary colonic tumour adenocarcinoma) and human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability over varying times. The loading efficiency of the drug brimonidine in the particles was shown to be between 80-85% and pH dependent. The bioadhesive polyacrylic hydrogel nanoparticles, used in the present study, exhibited superior loading properties for brimonidine, and the formulation was stable for more than 5 weeks. When the drug-loaded nanoparticles were dispersed in a phosphate buffer saline (pH = 7.4), the drug was slowly released over several hours. Two-photon laser scanning microscopic studies of dye-conjugated polyacrylic acid nanoparticles demonstrated the accumulation of the particles on the surface and intercellular spaces of Caco-2 cells.

Acrylic Resins↗