acyclovir and Hemolysis

To develop a suitable clinical laboratory assay for detecting the activity of circulating immune complexes (CICs) that activate complement (ACIC).. CICs measured in serum were initially used to activate complement, and the remaining complement was activated through sensitized human O-erythrocytes. ACIC was quantified by the degree of hemolysis. Each serum sample was tested for ten consecutive days to determine its stability. Reference ranges are suggested. ACIC was measured in both healthy individuals and patients with autoimmune diseases as well.. The OD values of the hemolysis degree index were inversely proportional to ACIC (r = -0.986, P = 0.002). A pooled serum was used to eliminate interference and optimize the experiment. The hemolysis degree (HD) was used to indicate the detection result. HD = (detection value OD/negative value OD)*100. Both the intra-batch and the inter-batch results showed good stability with a CV of 6.5% and 8.1%, respectively. HD differences between males and females were significant (P = 0.015) while the normal distribution for both genders was conformed. The HD recommended reference range for men is 56-88 while for women is 51-86. Serum HD of healthy subjects and autoimmune disease patients showed a significant difference (P = 0.001). Autoimmune disease patients have lower HD which was a result of having stronger ACIC.. The ACIC assay while utilizing human O-erythrocytes as an indicator system is sensitive and accurate, and has potential in clinical applications.

Topics: Acyclovir; Antigen-Antibody Complex; Autoimmune Diseases; Complement System Proteins; Erythrocytes; Female; Hemolysis; Humans; Male

Topics: Acyclovir; Antiviral Agents; Dyspnea; Enzyme Inhibitors; Hemolysis; Humans; Jaundice; Male; Methylene Blue; Middle Aged; Oxidative Stress; Renal Insufficiency; Treatment Outcome

The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.

Topics: Acyclovir; Animals; Antiviral Agents; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Delivery Systems; Female; Galactose; Glycolates; Hemolysis; Lactic Acid; Liver; Male; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Nanoparticles; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Spectroscopy, Fourier Transform Infrared; Surface Properties; Tissue Distribution

The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a β-cyclodextrin-poly(4-acryloylmorpholine) monoconjugate (β-CD-PACM), are proposed as acyclovir carriers. The experimental procedure necessary to obtain the acyclovir-loaded nanoparticles using the solvent displacement preparation method will be described in this chapter. Fluorescent labeled nanoparticles are prepared using the same method for cellular trafficking studies. The biocompatibility assays necessary to obtain safe nanoparticles are reported. Section 4 of this chapter describes the assessment of the antiviral activity of the acyclovir-loaded nanoparticles.

Topics: Acrylic Resins; Acyclovir; Animals; Antiviral Agents; beta-Cyclodextrins; Cell Survival; Chlorocebus aethiops; Complement Activation; Hemolysis; Herpesvirus 1, Human; Humans; Materials Testing; Nanocapsules; Particle Size; Reactive Oxygen Species; Skin; Surface Properties; Tissue Culture Techniques; Vero Cells; Viral Load; Viral Plaque Assay

Self-assembled drug delivery systems (SADDS) were designed in the paper. They can be prepared from the amphiphilic conjugates of hydrophilic drugs and lipids through self-assembling into small-scale aggregates in aqueous media. The outstanding characteristic of SADDS is that they are nearly wholly composed of amphiphilic prodrugs. The self-assembled nanoparticles (SAN) as one of SADDS had been prepared from the lipid derivative of acyclovir (SGSA) in the previous paper. They were further studied on the properties and the in vitro/in vivo behavior in this paper. The SAN kept the physical state stable upon centrifugation or some additives including some inorganic salts, alkaline solutions, surfactants and liposomes except for HCl solution, CaCl(2) solution and animal plasma. Autoclave and bath heat for sterilization hardly influenced the SAN. However, gamma-irradiation strongly destroyed the structure of SAN and SGSA was degraded. SGSA in SAN showed good stability in weak acidic or neutral buffers although it was very sensitive to alkaline solutions and carboxylester enzymes, the half-lives (t(1/2)) of which in the buffer at pH 7.4, the alkaline solution at pH 12.0, pig liver carboxylester enzyme solution, rabbit plasma, and rabbit liver tissue homogenate were 495, 21, 4.7, 25 and 8.7 h, respectively. Compared with SGSA in a disordered state, the specific bilayer structures of SAN could protect SGSA from hydrolysis through hiding the sensitive ester bonds. The SAN showed hemolytic action because the amphiphilic SGSA could insert into rabbit erythrocyte membranes. Both the high concentration of SGSA in samples and the long incubation time improved hemolysis. No hemolysis was observed if the additional volume of the SAN was less than 10% of rabbit whole blood in spite of the high concentration of SGSA. Plasma proteins could interfere the interaction between the SAN and erythrocytes by binding the SAN. The in vitro antiviral activity of acyclovir SAN was limited possibly because of the weak hydrolysis of SGSA in Vero cells, and the SAN showed a little cell toxicity possible due to the amphiphilicity of SGSA. A macrophage cell line of QXMSC1 cells showed uptake of the SAN but not significantly. The SAN were rapidly removed from blood circulation after bolus iv administration to rabbits with the very short distribution t(1/2) (1.5 min) and the elimination t(1/2) (47 min). The SAN were mainly distributed in liver, spleen and lung after iv administration, and SGSA

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Drug Delivery Systems; Drug Stability; Hemolysis; Herpesvirus 1, Human; Injections, Intravenous; Lipids; Microbial Sensitivity Tests; Nanostructures; Rabbits; Tissue Distribution; Vero Cells