Amylin is a pancreatic hormone cosecreted with insulin that exerts unique roles in metabolism and glucose homeostasis. The therapeutic restoration of postprandial and basal amylin levels is highly desirable in diabetes mellitus. Protein conjugation with the biocompatible polymer polyethylene glycol (PEG) has been shown to extend the biological effects of biopharmaceuticals. We have designed a PEGylated human amylin by using the aminoreactive compound methoxylpolyethylene glycol succinimidyl carbonate (mPEGsc). The synthesis in organic solvent resulted in high yields of monoPEGylated human amylin, which showed large stability against aggregation, an 8 times increase in half-life in vivo compared to the non-conjugated amylin, and pharmacological activity as shown by modulation of cAMP production in MCF–7 cell line, decrease in glucagon and modulation of glycemia following subcutaneous administration in mice. Altogether these data reveal the potential use of PEGylated human amylin for the restoration of fasting amylin levels.
Amylin is a pancreatic hormone involved in the regulation of glucose metabolism and homeostasis. Restoration of the post-prandial and basal levels of human amylin in diabetic individuals is a key in controlling glycemia, controlling glucagon, reducing the insulin dose and increasing satiety, among other physiologic functions. Human amylin has a high propensity to aggregate. We have addressed this issue by designing a liposomal human amylin formulation. Nanoparticles of multilamellar liposomes comprising human amylin were obtained with 53% encapsulation efficiency. The in vitro kinetic release assay shows a biphasic profile. The stabilization of the lipidic nanoparticle against freeze-drying was achieved by using mannitol as a cryoprotectant, as evidenced by morphological characterization. The effectiveness of the human amylin entrapped in lipidic nanoparticles was tested by the measurement of its pharmacological effect in vivo after subcutaneous administration in mice. Collectively these results demonstrate the compatibility of human amylin with the lipidic interface as an effective pharmaceutical delivery system.
1457 Artigo Chemical Composition and Anticariogenic Activity of Tambja stegosauriformis Nudibranch Braga, R. R.;* Iorio, N. L. P. P; Póvoa, H. C. C.; Chianca, G. C.; Kachlicki, P.; Ożarowski, M.; Silva, V. O.; Félix, H. P.; Lopes, I. C.; Chaves, D. S. A.Resumo: Extrato do nudibrânquio da espécie Tambja stegosauriformis foi obtido por imersão em metanol, concentrados em um rotaevaporador e secos por liofilização. A identificação dos metabólitos secundários presentes nos extratos foi realizada por cromatografia líquida de alta eficiência com detector DAD, acoplada à espectrometria de massa (HPLC-DAD-MSn). Foram identificados oito alcaloides pirrólicos no extrato de T. stegosauriformis. Todos os alcaloides derivam da estrutura base com dois anéis pirrólicos interligados e presença de bromo ou não, as quais foram reportadas previamente na literatura. A atividade antibacteriana do extrato foi testada em amostras padrão de Strepcococcus mutans ATCC ("American Type Culture Collection") 25175 e Lactobacillus casei ATCC 393, determinando a Concentração Inibitória Mínima (CIM) e Concentração Bactericida Mínima (CBM) do extrato frente a essas bactérias. A atividade citotóxica das concentrações do extrato de T. stegosauriformis com atividade antibacteriana foi verificada em Artemia salina. O extrato de T. stegosauriformis apresentou atividade bacteriostática frente às espécies S. mutans (CIM = 1,175mg / mL) e L. casei (CIM = 0,5875 mg / mL). Os resultados indicam um potencial efeito anticariogênico de substâncias presentes no extrato do nudibrânquio T. stegosauriformis Palavras-chave: Nudibrânquios; produtos naturais marinhos; alcaloides pirrólicos; atividade antimicrobiana AbstractExtract from Tambja stegosauriformis nudibranch were obtained by immersion in methanol, concentrated in a rotary evaporator and dried by lyophilization. The identification of the secondary metabolites present in the extracts was performed by high performance liquid chromatography with DAD detector, coupled to mass spectrometry (HPLC-DAD-MSn). Eight pyrrole alkaloids were identified in the T. stegosauriformis extract. All alkaloids identified and reported previously in the literature are derived from the base structure of two interconnected pyrrole rings, some compounds are substituted with bromine. The antibacterial activity of the extracts was tested on Streptococcus mutans ATCC (American Type Culture Collection) 25175 and Lactobacillus casei ATCC 393 samples, determining the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the extract against these bacteria. The cytotoxic activity against Artemia salina was detected in the T. stegosauriformis extract with antibacterial activity. The T. stegosauriformis extract presented bacteriostatic activity against S. mutans (MIC = 1.175mg / mL) and L. casei (MIC = 0.5875 mg / mL). The results indicate a potential anticariogenic effect of substances present in the T. stegosauriformis extract.
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