ABSTRACT
Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.
Subject(s)
Drug Carriers/chemistry , Erythrocyte Membrane/chemistry , Ferric Compounds/chemistry , Fluorescent Dyes/chemistry , Magnetic Iron Oxide Nanoparticles/chemistry , Magnets/chemistry , Manganese Compounds/chemistry , Photothermal Therapy/methods , Animals , Carcinoma, Ehrlich Tumor/drug therapy , Disease Models, Animal , Drug Carriers/pharmacokinetics , Female , Ferric Compounds/pharmacokinetics , Fluorescent Dyes/pharmacokinetics , Hyperthermia, Induced/methods , Manganese Compounds/pharmacokinetics , Mice , Particle Size , Theranostic Nanomedicine/methods , Tissue Distribution , Tumor Burden/drug effects , Tumor Microenvironment/drug effectsABSTRACT
A esquistossomose mansônica é uma doença infecciosa parasitária, causada por um trematódeo (Schistosoma mansoni) que vive na corrente sanguínea do hospedeiro definitivo, cuja evolução clínica pode variar desde formas assintomáticas até as extremamente graves. O presente relato teve como objetivo fazer o registro de um caso de esquistossomose em um indivíduo aparentemente sadio que, por razões de seu trabalho, circula continuamente por áreas endêmicas e por diversos municípios do estado de Goiás, região não endêmica, comprovando, assim, o papel das migrações na disseminação desta parasitose.
Schistosomiasis mansoni is a parasitic infectious disease caused by a trematode (Schistosoma mansoni) that lives in the bloodstream of their definitive host, whose clinical course can vary from asymptomatic to extremely serious involvement. Thisreport aims to register a case of schistosomiasis in an individual, apparently healthy, for a labor that constantly circulates between endemic areas and in several counties in the state of Goias, a non-endemic region, thus demonstrating the role of migrationon the spread of this disease.
Subject(s)
Humans , Male , Adult , Biomphalaria , Schistosomiasis/diagnosis , Schistosomiasis/epidemiology , Sanitation , Schistosoma mansoni/parasitology , Brazil/epidemiology , Rural AreasABSTRACT
The objective of the present work was to register the first proven cases of human pseudomyiasis due to Eristalis tenax in Goiás State, Brazil, underscoring their clinical manifestations and direct relationship with hygiene. The taxonomic identification of the instars was done according to the descriptions and keys presented by James (1947), Hartley (1961) and Guimarães & Papavero (1999). Two cases were observed. In both cases there was no evidence of apparent mental disturbance. The clinical picture of these cases was self limited. The water supply, sewer system, socioeconomic level and habits of the suspect species of the flies are criteria that should be investigated.
Subject(s)
Diptera , Feces/parasitology , Gastrointestinal Diseases/parasitology , Myiasis/parasitology , Adult , Animals , Female , Gastrointestinal Diseases/diagnosis , Humans , Infant , Larva , Male , Myiasis/diagnosisABSTRACT
O presente trabalho visa registrar os primeiros casos evidenciados de pseudomiíases humanos por Eristalis tenax no estado de Goiás, Brasil, destacando suas manifestações clínicas e suas relações diretas com os hábitos higiênicos. A identificação taxonômica das larvas foi realizada com base nas descrições e chaves apresentadas por James (1947), Hartley (1961) e Guimarães & Papavero (1999). Observaram-se dois casos. Em ambos não havia evidência de pertubações mentais claras. O quadro clínico de ambos os casos era mesmo limitado. O abastecimento de água, o nível sócio-econômico e o hábito das espécies das moscas são critérios que devem ser considerados na investigação.
