No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Development of a Synthetic Blood Substitute Utilizing Hemoglobin Vesicles
Abstract
The overall goal of our study was to further the development of a safe and effective oxygen-carrying red blood cell (RBC) substitute based on functional hemoglobin encapsulated within lipid vesicles (liposomes). Our studies demonstrated that liposome-encapsulated hemoglobin (LEH) provided an effective means of oxygen delivery in experimental animals. Our results indicated that exposure of experimental animal to liposomes made from conventional lipids was associated with significant immunotoxicity, as measured by impaired host resistance to infectious challenge. Our results thus far suggested that liposomes constructed with Stealth lipids were less immunotoxic than were liposomes made with conventional lipids. Both LEH formulations depressed phagocytic function as measured by ingestion of latex beads. Circulation half-life following 50% isovolumic exchange-transfusion in rats with LEH was about 20 hrs; 97% exchange-transfusion demonstrated efficacy in life support Met-Hb generation accompanying LEH processing (below 10 deg C) and 1 month storage (-20 deg C) appeared to be small with only a 3% and less than a 10% increase for encapsulated over precursor, respectively Oxygen affinity and cooperativity and steady shear viscosity values for LEH suspensions (30% by volume) appeared to be near the normal values expected for whole blood. Incubation in plasma at 37 deg C resulted in only a sm all amount of Hb release from LEH; also shear had very little effect on causing Hb leakage from LEH.
Abstract: Haem is found in all living cells as well tissues in the form of proteins suchas cytochromes, hemoglobin’s and peroxides. This is act as catalyst for theformation of oxygen radicals. Encapsulation of haem or hemoglobin with in lipidvesicles or liposome’s is called “Hemosomes” or it is also called Liposomeencapsulatedhemoglobin (LEH). Which are 0.1 to 10 microns in dimension, andit is a technology of preparing artificial red blood substitutes. The synthetic cellsare stable being somewhat smaller and stronger than normal red blood cells andare having same electrophoretic movements. Hemoglobin (Hb) encapsulationwithin a liposome is one of the strategies in the development of artificial oxygen
carriers. The review article includes preparation techniques, characterizationand stability of Hemosomal drug delivery system.
Simple approximations, like the Eddington, are often incapable of coping with the highly asymmetric phase functions typical of particulate scattering. A simple yet accurate method called the delta-Eddington approximation is proposed for determining monochromatic radiative fluxes in an absorbing-scattering atmosphere. In this method, the governing phase function is approximated by a Dirac delta function forward scatter peak and a two-term expansion of the phase function. The fraction of scattering into the truncated forward peak is taken proportional to the square of the phase function asymmetry factor, which distinguishes the delta-Eddington approximation from others of similar nature. The transmission, reflection, and absorption predicted by the delta-Eddington approximation are compared with doubling method calculations for realistic ranges of optical depth, single-scattering albedo, surface albedo, sun angle and asymmetry factor. The approximation is shown to provide an accurate and analytically simple parameterization of radiation to replace the empirism currently encountered in many general circulation and climate models.
The known optical properties (absorption, scattering, total
attenuation, effective attenuation, and/or anisotropy coefficients) of
various biological tissues at a variety of wavelengths are reviewed. The
theoretical foundations for most experimental approaches are outlined.
Relations between Kubelka-Munk parameters and transport coefficients are
listed. The optical properties of aorta, liver, and muscle at 633 nm are
discussed in detail. An extensive bibliography is provided
The propagation of light energy in tissues is an important problem in phototherapy, especially with the increased use of lasers as light sources. Often a slight difference in delivered energy separates a useless, efficacious, or disastrous treatment. Methods are presented for experimental characterization of the optical properties of a tissue and computational prediction of the distribution of light energy within a tissue. A standard integrating sphere spectrophototneter measured the total transmission, Tt, total reflectance, Rt, and the on-axis transmission, Ta, for incident collimated light that propagated through the dermis of albino mouse skin, over the visible spectrum. The diffusion approximation solution to the one-dimensional (1-D) optical transport equation computed the expected Tt, and Rt, for different combinations of absorbance, k, scattering, s, and anisotropy, g, and by iterative comparison of the measured and computed Tt, and Rt, values converged to the intrinsic tissue parameters. For example, mouse dermis presented optical parameters of 2.8 cm−1, 239 cm−1, and 0.74 for k,s, and g, respectively, at 488 nm wavelength. These values were used in the model to simulate the optical propagation of the 488-nm line of an argon laser through mouse skin in vivo. A 1-D Green's function thermal diffusion model computed the temperature distribution within the tissue at different times during laser irradiation. In vitro experiments showed that the threshold temperature range for coagulation was 60°–70° C, and the kinetics were first order, with a temperature-dependent rate constant that obeyed an Arrhenius relation (molar entropy 276 cal/mol-°K, molar enthalpy 102 kcal/mol). The model simulation agreed with the corresponding in vivo experiment that a 2-s pulse at 55 W/cm2 irradiance will achieve coagulation of the skin.
Optical constants of animal and plant tissues were measured over a wide spectral range using an integrating sphere spectrophotometer. The data were analyzed with two formulations of the 1-D diffusion approximation differing in the phase function. The accuracy of the similarity transformation was examined with tissue phantoms incorporating known chromophores in light scattering media.
The scattering and absorption of light by randomly oriented, discretely scattering, red blood cells imbedded in a homogeneous plasma medium can be described by the P1 approximation to the one-speed transport equation, where the cells have the dual role of anisotropic sources for first scattering events and of scattering and absorption sites for subsequent scattering events. Equations for diffuse reflectance defined for a finite size receiver in the plane of a normally incident cylindrical photon beam are derived and compared with experimental data to fundamentally justify the basic sending-receiving characteristics of a fiber optic catheter model. A model of the fiber optic catheter used for the spectrophotometric measurement of oxygen content in blood is developed from the theory and compared with experimental results to further substantiate the theoretical approach.
A light dosimetry model for photodynamic therapy is described leading to the dependence of necrosis depth on incident light dose. Semiempirical dosimetry relations are derived for four modes of light delivery. Results for Photofrin II at 630 nm are summarized in graphical form. Numerical values of the parameters and necrosis depth calculations are compared with literature data.
Malnourished patients frequently received parenteral nutrition with Intralipid, a lipid emulsion that accumulates in the reticuloendothelial tissue in some patients. To examine the potential of this emulsion as a risk factor for infection, I evaluated its effect on peritoneal clearance processes and on macrophage function. Mice treated with Intralipid (0.5 ml intraperitoneally) twice daily for 4 days had delayed clearance of Staphylococcus aureus from the peritoneal cavity and had increased staphylococcal dissemination to renal tissue. However, this regimen did not alter the neutrophil influx into the peritoneum elicited by this bacterial challenge. Intralipid also delayed the clearance of inert carbon particles from the peritoneal cavity. Peritoneal macrophages incubated with Intralipid (40% vol/vol) in tissue culture media for 18 hr became rounded and more phase dense, and these cells had multiple homogeneous cytoplasmic deposits. This Intralipid exposure reduced phagocytic and pinocytic activities in these monolayers, and the phagocytic defect persisted for at least 24 hr after cells were removed from media supplemented with Intralipid. In summary, these results demonstrate that Intralipid inhibits peritoneal clearance processes and that this alteration probably reflects impaired macrophage (free cells) and reticuloendothelial function. In some patients this form of nutritional therapy may increase the risk of infection.
A Monte Carlo computer model has been developed to study the propagation of light in tissues. Light attenuation is assumed to result from absorption and isotropic scattering. The model has been used to predict the distribution of absorbed dose in homogeneous tissues of different absorption/scattering ratios, for illumination both by external light beams and via implanted optical fibers. The photon flux into optical fibers placed in the tissue as detectors has also been investigated. The results are interpreted in relation to the use of visible light irradiation for photo radiation therapy.