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Int J Nanomedicine ; 14: 7643-7663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571869


Angiogenesis is the formation of new blood vessels from pre-existing vessels. It is a highly regulated process as determined by the interplay between pro-angiogenic and anti-angiogenic factors. Under certain conditions the balance between angiogenesis stimulators and inhibitors is altered, which results in a shift from physiological to pathological angiogenesis. Therefore, the goal of therapeutic targeting of angiogenic process is to normalize vasculature in target tissues by enhancing angiogenesis in disease conditions of reduced vascularity and blood flow, such as tissue ischemia, or alternatively to inhibit excessive and abnormal angiogenesis in disorders like cancer. Gold nanoparticles (AuNPs) are special particles that are generated by nanotechnology and composed of an inorganic core containing gold which is encircled by an organic monolayer. The ability of AuNPs to alter vasculature has captured recent attention in medical literature as potential therapeutic agents for the management of pathologic angiogenesis. This review provides an overview of the effects of AuNPs on angiogenesis and the molecular mechanisms and biomedical applications associated with their effects. In addition, the main synthesis methods, physical properties, uptake mechanisms, and toxicity of AuNPs are briefly summarized.

Tecnologia Biomédica/métodos , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Endocitose , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade
Clin Pharmacol ; 10: 23-29, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29551915


Background: Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus. Objectives: To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53. Materials and methods: The antiproliferative effect of pramlintide alone or in combination with 5-fluorouracil, oxaliplatin, or irinotecan in HCT-116 and HT-29 colorectal cancer cell lines was investigated using MTT cell proliferation assay. IC50 values were calculated using Compusyn software 1.0. Synergy values (R) were calculated using the ratio of IC50 of each primary drug alone divided by combination IC50s. For each two pairs of experiments, Student's t-test was used for analysis. For combination studies, one-way analysis of variance and Tukey post hoc testing was performed using R 3.3.2 software. A p-value of <0.05 was considered significant. Results: Pramlintide inhibited the growth of HCT-116 and HT-29 in a dose-dependent manner, with higher efficacy against the latter (IC50s; 48.67 and 9.10 µg/mL, respectively; p-value =0.013). Moreover, the addition of 5, 10, and 20 µg/mL of pramlintide to HCT-116 and HT-29 with 5-fluorouracil, oxaliplatin, or irinotecan induced the antiproliferative effect synergistically (R>1.6, p-value <0.05). Conclusion: Pramlintide enhances the cytotoxicity of conventional chemotherapy against colorectal cancer cell lines harboring wild-type or mutant p53. Thus, pramlintide is a promising potential adjuvant chemotherapy in colorectal cancer.

Eur J Pharm Sci ; 115: 68-76, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29337216


As a promising long-acting inhaled formulation, liposomal ciprofloxacin (Lipo-CPFX) was characterized in the in vitro human lung epithelial Calu-3 cell monolayer system, compared to ciprofloxacin in solution (CPFX). Its modulated absorptive transport and uptake, and sustained inhibitory activity against induced pro-inflammatory interleukin-8 (IL-8) release were examined. The absorptive transport and uptake kinetics for Lipo-CPFX and CPFX were determined at 0.1-50 mg/ml in the Transwell system. The Lipo-CPFX transport was then challenged for mechanistic exploration via cell energy depletion, a reduced temperature, endocytosis and/or lipid fusion inhibition, and addition of excess non-loaded liposomes. The inhibitory activities of Lipo-CPFX and CPFX against lipopolysaccharide (LPS)-induced IL-8 release were assessed in a co-incubation or pre-incubation mode. In the tight Calu-3 cell monolayers, Lipo-CPFX yielded 15-times slower ciprofloxacin flux of absorptive transport and 5-times lower cellular drug uptake than CPFX. Its transport appeared to be transcellular; kinetically linear, proportional to encapsulated ciprofloxacin concentration; and consistent with the cell energy-independent lipid bilayer fusion mechanism. Lipo-CPFX was equipotent to CPFX in the anti-IL-8 releasing activity upon 24 h co-incubation with LPS. Additionally, Lipo-CPFX, but not CPFX, retained the anti-IL-8 releasing activity even 24 h after pre-incubation. In conclusion, Lipo-CPFX enabled slower absorptive lung epithelial cell transport and uptake of ciprofloxacin, apparently via the lipid bilayer fusion mechanism, and the sustained inhibitory activity against LPS-induced IL-8 release, compared to CPFX.

Ciprofloxacino/farmacologia , Células Epiteliais/efeitos dos fármacos , Interleucina-8/antagonistas & inibidores , Lipossomos/química , Lipossomos/farmacologia , Pulmão/efeitos dos fármacos , Linhagem Celular , Ciprofloxacino/química , Células Epiteliais/metabolismo , Humanos , Bicamadas Lipídicas/metabolismo , Pulmão/metabolismo