Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture.

PURPOSE: This work investigated the endocytic pathways taken by poly(isobutylcyanoacrylate) (PIBCA) nanoparticles differing in their surface composition and architecture, assuming that this might determine their efficiency of intracellular drug delivery. METHODS: Nanoparticles (A0, A25, A100, R0, R25 ) were prepared by anionic or redox radical emulsion polymerization using mixtures of dextran and fucoidan (0, 25, 100 % in fucoidan). Cell uptake was evaluated by incubating J774A.1 macrophages with nanoparticles. Endocytic pathways were studied by incubating cells with endocytic pathway inhibitors (chlorpromazine, genistein, cytochalasin D, methyl-ß-cyclodextrin and nocodazole) and nanoparticle uptake was evaluated by flow cytometry and confocal microscopy. RESULTS: The fucoidan-coated PIBCA nanoparticles A25 were internalized 3-fold more efficiently than R25 due to the different architecture of the fucoidan chains presented on the surface. Different fucoidan density and architecture led to different internalization pathway preferred by the cells. Large A100 nanoparticles with surface was covered with fucoidan chains in a loop and train configuration were internalized the most efficiently, 47-fold compared with A0, and 3-fold compared with R0 and R25 through non-endocytic energy-independent pathways and reached the cell cytoplasm. CONCLUSION: Internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. In turn, this influenced the extent of internalization and localization of accumulated nanoparticles within cells. The results are of interest for rationalizing the design of nanoparticles for potential cytoplamic drug delivery by controlling the nature of the nanoparticle surface.

Antimicrobial activity of ß-lapachone encapsulated into liposomes against meticillin-resistant Staphylococcus aureus and Cryptococcus neoformans clinical strains.

The aim of this study was to determine whether encapsulation of ß-lapachone (ß-lap) into liposomes interferes with its in vitro antimicrobial activity against meticillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans clinical strains. Liposomes (ß-lap:lipo or ß-lap:HPß-CD-lipo) were prepared using the hydration of thin lipid film method followed by sonication. The in vitro antimicrobial activities of ß-lap-loaded liposomes against MRSA and C. neoformans were evaluated using the microdilution method according to the Clinical and Laboratory Standards Institute (CLSI). The liposomes presented a mean particle size ranging from 88.7±1.5nm to 112.4±1.9nm with a polydispersity index ranging from 0.255 to 0.340, zeta potential from -0.26±0.01mV to +0.25±0.05mV and drug encapsulation efficiency from 97.4±0.3% to 98.9±0.4%. ß-Lap and ß-lap:HPß-CD had minimum inhibitory concentrations (MICs) ranging from 2mg/L to 4mg/L, whereas the MICs of ß-lap-lipo or ß-lap:HPß-CD-lipo ranged from 4mg/L to 16mg/L for the MRSA strains tested. ß-Lap and ß-lap:HPß-CD were able to inhibit fungal growth [MIC=2-8mg/L and minimum fungicidal concentration (MFC)=4-8mg/L]. However, ß-lap-lipo and ß-lap:HPß-CD-lipo were more efficient, with MICs and MFCs of <4mg/L. These findings suggest that the liposomal formulations tested do not interfere significantly with ß-lap antibacterial activity against MRSA and improve its antifungal properties against C. neoformans.

Monensina na engorda de novilhos mestiços Zebu X Angus sob pastejo / Monensin for finishing of crossbred steers on pasture

Estudou-se o efeito da monensina adicionada ao suplemento mineral sobre o peso de bovinos mestiços, criados sob pastejo, e seus efeitos sobre os rendimentos da carcaça. O trabalho foi conduzido no município de Carlos Chagas, MG, de agosto de 1994 a janeiro de 1995. Utilizaram-se 82 animais inteiros, mestiços Zebu X Europeu (14 1/4 europeu, filhos de touro P; 32 1/2 europeu, filhos de touros L e 36 1/4 europeu, filhos de touro SS) com peso e idade médios iniciais, respectivamente, de 350kg e 18 meses. Os 82 animais foram seqüencialmente sorteados dentro de peso inicial, touro ou grau de sangue em três tratamentos: T1 (n=28), grupo-controle; T2 (n=26), recebendo 3 por cento de rumensin (10 por cento de monensina) adicionado ao suplemento mineral (18 por cento de NaCl, 16 por cento de farelo de algodäo, 15 por cento de farelo de milho, 5 por cento de melaço, 20 por cento de uréia, 12 por cento de farinha de osso, 12,8 por cento de ortofosfato e 1,2 por cento de microminerais); T3 (n=28), idem ao T2, adicionado de 3 por cento de levedura de cana de açúcar (palatabilizante). Todos os animais permaneceram em pastagens de coloniäo. Näo houve diferença (P>0,05) no peso final dos animais dos grupos T1 e T2, mas os do grupo T3 apresentaram ganho de peso superior (P<0,01). O peso médio final foi de 510,19ñ3,01kg para T1; 505,84ñ3,14kg para T2 e 522,47ñ3,00kg para T3 (P<0,01). Animais filhos do touro P apresentaram peso médio final de 516,78ñ4,24kg comparado com 515,55ñ2,73 e 506,16ñ2,64kg, respectivamente, para touros L e SS (P<0,05). Näo se observou efeito da monensina (P>0,05) sobre o rendimento da carcaça