Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan

Purpose: Poly (L-lactic acid) (PLA) microparticles encapsulating Hepatitis B surface antigen (HBsAg) with alum and chitosan were investigated for their potential as a vaccine delivery system. Methods: The microparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method with polyvinyl alcohol (PVA) or chitosan as the external phase stabilising agent showed a significant increase in the encapsulation efficiency of the antigen. Results: PLA-Alum and PLA-chitosan microparticles induced HBsAg serum specific IgG antibody responses significantly higher than PLA only microparticles and free antigen following subcutaneous administration. Chitosan not only imparted a positive charge to the surface of the microparticles but was also able to increase the serum specific IgG antibody responses significantly. Conclusions: The cytokine assays showed that the serum IgG antibody response induced is different according to the formulation, indicated by the differential levels of interleukin 4 (IL-4), interleukin 6 (IL-6) and interferon gamma (IFN-γ). The microparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-4, IL-6 and IFN-γ

Reaction of ruthenium phenyl acetylide with iron-chalcogen clusters and iron pentacarbonyl

Photolysis of a THF solution containing ruthenium acetylide [(eta(5)-C5H5)Ru(PPh3)(2)(eta(1)-C CPh)] with [Fe-3(CO)(9)(mu(3)-Se)(2)] cluster affords an adduct [{mu-SeC(CpRu(PPh3)(CO))=C(Ph)Se)(CO)(6)Fe-2] (1), while under similar reaction condition with [Fe-3(CO)(9)(mu(3)-Te)(2)] cluster a Ru-inserted product [(eta(5)-C5H5)(PPh3)(eta(1)-C CPh)RuFe2(mu(3)-Te)(2)(CO)(6)] (2) was obtained. Under thermal condition [(eta(5)-C5H5)Ru(PPh3)(2)(eta(1)-C CPh)] react with Fe(CO)(5) to give an acetylide stabilised Fe2Ru mixed metal cluster [(eta(5)-C5H5)RuFe2(CO)(7)(eta(2):eta(2):eta(1)-C=CPh)], (3). (C) 2013 Elsevier B.V. All rights reserved

Cleavage of phosphorus-sulfur bond and formation of (mu(4)-S)Fe-4 core from photochemical reactions of Fe(CO)(5) with [(RO)(2)PS2](2); (R = Me, Et, Pr-i)

When hexane or alcohol solutions containing iron pentacarbonyl and bis(dialkoxythiophosphoryl) disulfide (R= Me (1), Et (2), or Pr-i (3)), were irradiated with 366 nm light, under argon atmosphere at 0 degrees C, clusters [(mu-RS)Fe-2(CO)(6)](mu(4)-S)[(mu-(OR)(2)P)Fe-2(CO)(6)] (4: R = Me, 5: R = Et) and [Fe-2(CO)(6)S{P((OPr)-Pr-i)2}](2) (6) were obtained in hexane and [Fe-4(CO)(8)(mu-CO)(2)(mu(4)-S)(2)P(OR)(3)] (7: R = Me, 8: R = Et) in MeOH and EtOH respectively. These reactions involve P-S bond cleavage of ligands and desulfurization process and Fe-S and Fe-P bond formation. Computational and experimental bond parameters have been studied on the new compounds. (C) 2017 Elsevier B.V. All rights reserved

Role of Sulfur in Influencing Contrasting Reactivity of Acetylene Bonds in 1-Ferrocenyl-4-phenyl-1,3-butadiyne in Cluster Forming Reaction

Photolysis of a hexane solution containing Fe(CO)(5), 1-ferrocenyl-4-phenyl-1,3-butadiyne and sulfur powder, under argon at 0 A degrees C led to the formation of [mu(3)-eta(1):eta(2):eta(1)-{C(Ph)=C(Ca parts per thousand CFc)}(mu(3)-S)Fe-3(CO)(9)] (1), [mu(3)-eta(2):eta(1)-{C(Fc)=C(Ca parts per thousand CPh)}(mu(3)-S)Fe-2(CO)(6)] (2), [Fe-2(CO)(6){(mu-S)(2)C(Fc)=C(Ca parts per thousand CPh)}] (3), and [Fe-2(CO)(6){(mu-SC(O)C(Fc)=C(Ca parts per thousand CPh)S}] (4) featuring new C-C, Fe-C, Fe-Fe and Fe-S bond formations. All new compounds were characterized by IR and H-1 and C-13 NMR spectroscopy. Structures of 1-3 were established crystallographically. Compound 4 was established by mass, IR, and H-1 NMR and C-13 NMR spectroscopy. Photolysis of a hexane solution containing Fe(CO)(5), 1-ferrocenyl-4-phenyl-1,3-butadiyne and sulfur powder, under argon at 0 A degrees C led to the formation of [mu(3)-eta(1):eta(2):eta(1)-{C(Ph)=C(Ca parts per thousand CFc)}(mu(3)-S)Fe-3(CO)(9)] (1), [mu(3): eta(2):eta(1)-{C(Fc)=C(Ca parts per thousand CPh)}(mu(3)-S)Fe-2(CO)(6)] (2), [Fe-2(CO)(6){(mu-S)(2)C(Fc)=C(Ca parts per thousand CPh)}] (3), and [Fe-2(CO)(6){(mu-SC(O)C(Fc)=C(Ca parts per thousand CPh)S}] (4) featuring new C-C, Fe-C, Fe-Fe and Fe-S bond formations. All new compounds were characterized by IR and H-1 and C-13 NMR spectroscopy. Structures of 1-3 were established crystallographically. Compound 4 was established by mass, IR and H-1 NMR and C-13 NMR spectroscopy

Nanoprecipitation versus emulsion-based techniques for the encapsulation of proteins into biodegradable nanoparticles and process-related stability issues

The goal of this study was to investigate the entrapment of 3 different model proteins (tetanus toxoid, lysozyme, and insulin) into poly(D,L-lactic acid) and poly(D,L-lactic-co-glycolic acid) nanoparticles and to address process-related stability issues. For that purpose, a modified nanoprecipitation method as well as 2 emulsion-based encapsulation techniques (ie, a solid-in oil-in water (s/o/w) and a double emulsion (w1/o/w2) method) were used. The main modification of nanoprecipitation involved the use of a wide range of miscible organic solvents such as dimethylsulfoxide and ethanol instead of the common acetone and water. The results obtained showed that tetanus toxoid and lysozyme were efficiently incorporated by the double emulsion procedure when ethyl acetate was used as solvent (>80% entrapment efficiency), whereas it was necessary to use methylene chloride to achieve high insulin entrapment efficiencies. The use of the s/o/w method or the formation of a more hydrophobic protein-surfactant ion pair did not improve protein loading. The nanoprecipitation method led to a homogenous population of small nanoparticles (with size ranging from ≈130 to 560 nm) and in some cases also improved experimental drug loadings, especially for lysozyme (entrapment efficiency >90%). With respect to drug content determination, a simple and quick matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method provided results very close to those obtained by reverse phase-high-performance liquid chromatography. With respect to protein stability, the duration and intensity of sonication were not a concern for tetanus toxoid, which retained more than 95% of its antigenicity after treatment for 1 minute. Only a high methylene chloride:water ratio was shown to slightly decrease toxoid antigenicity. Finally, no more than 3.3% of A21 desamido insulin and only traces of covalent insulin dimer were detected in nanoparticles. In conclusion, both the double emulsion and nanoprecipitation methods allowed efficient protein encapsulation. MALDI-TOF MS allowed accurate drug content determination. The manufacturing processes evaluated did not damage the primary structure of insulin