gamma-cyclodextrin and Hemolysis

It is urgently needed to develop novel adjuvants for improving the safety and efficacy of vaccines. Metal-organic frameworks (MOFs), with high surface area, play an important role in drug delivery. With perfect biocompatibility and green preparation process, the γ-cyclodextrin metal-organic framework (γ-CD-MOF) fabricated with cyclodextrin and potassium suitable for antigen delivery. In this study, we modified γ-CD-MOF with span-85 to fabricate the SP-γ-CD-MOF as animal vaccine adjuvants. The ovalbumin (OVA) as the model antigen was encapsulated into particles to investigate the immune response. SP-γ-CD-MOF displayed excellent biocompatibility

Topics: Adjuvants, Vaccine; Animals; Animals, Outbred Strains; Bone Marrow Cells; Cell Survival; Chemistry, Pharmaceutical; Cytokines; Female; gamma-Cyclodextrins; Hemolysis; Immunoglobulin G; Metal-Organic Frameworks; Mice; Ovalbumin; Random Allocation; RAW 264.7 Cells; Spleen

In this study, cyclodextrin-based aqueous eye drop suspension of the water insoluble drug telmisartan was developed. Formation of a drug/γ-cyclodextrin complex was enabled by preventing formation of a poorly water-soluble zwitterion using a volatile base that was removed upon drying of the complex powder. Hydroxypropyl methylcellulose was shown to have the overall best effect, stabilizing the complexes without hampering the drug release from the formulation. Two strategies for preparing cyclodextrin-based aqueous eye drop suspensions of telmisartan were investigated, one where hydroxypropyl methylcellulose was added to the medium during preparation of the drug/γ-cyclodextrin complex powder (ternary complex) and the other where hydroxypropyl methylcellulose was added to the complex powder after preparation of the complex (binary complex). The complexation was characterized by DSC, FT-IR and (1)H NMR and the eye drop suspensions formed were examined regarding their stability and in vitro mucoadhesion property. The ternary complex exhibited inferior mucoadhesive property compared to the binary complex. However, the ternary complex was more stable as no notable change in particle size and particle size distribution was observed during storage at 4°C over 6 months (p<0.05) with the mean particle size determined between 2.0 and 2.5μm.

Topics: Adhesiveness; Animals; Benzimidazoles; Benzoates; Dose-Response Relationship, Drug; Drug Liberation; Drug Stability; Freeze Drying; gamma-Cyclodextrins; Hemolysis; Hypromellose Derivatives; Ophthalmic Solutions; Particle Size; Permeability; Sheep; Solubility; Suspensions; Telmisartan; Water

The present study investigated the hemolytic properties of fullerene (C(60)) nanoparticles prepared by solvent exchange using tetrahydrofuran (nC(60)THF), or by mechanochemically assisted complexation with macrocyclic oligosaccharide gamma-cyclodextrin (nC(60)CDX) or the copolymer ethylene vinyl acetate-ethylene vinyl versatate (nC(60)EVA-EVV). The spectrophotometrical analysis of hemoglobin release revealed that only nC(60)THF, but not nC(60)CDX or nC(60)EVA-EVV, was able to cause lysis of human erythrocytes in a dose- and time-dependent manner. Atomic force microscopy revealed that nC(60)THF-mediated hemolysis was preceded by erythrocyte shrinkage and increase in cell surface roughness. A flow cytometric analysis confirmed a decrease in erythrocyte size and demonstrated a significant increase in reactive oxygen species production in red blood cells exposed to nC(60)THF. The nC(60)THF-triggered hemolytic activity was efficiently reduced by the antioxidants N-acetylcysteine and butylated hydroxyanisole, as well as by serum albumin, the most abundant protein in human blood plasma. These data indicate that nC(60)THF can cause serum albumin-preventable hemolysis through oxidative stress-mediated damage of the erythrocyte membrane.

Topics: Erythrocytes; Fullerenes; Furans; gamma-Cyclodextrins; Hemolysis; Humans; Nanoparticles; Oxidative Stress; Polyvinyls; Serum Albumin