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1.
J Am Chem Soc ; 134(4): 1902-5, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22239619

RESUMO

A water-soluble polyphosphonium polymer was synthesized and directly compared with its ammonium analog in terms of siRNA delivery. The triethylphosphonium polymer shows transfection efficiency up to 65% with 100% cell viability, whereas the best result obtained for the ammonium analog reaches only 25% transfection with 85% cell viability. Moreover, the nature of the alkyl substituents on the phosphonium cations is shown to have an important influence on the transfection efficiency and toxicity of the polyplexes. The present results show that the use of positively charged phosphonium groups is a worthy choice to achieve a good balance between toxicity and transfection efficiency in gene delivery systems.


Assuntos
Portadores de Fármacos/farmacologia , Compostos Organofosforados/farmacologia , Polímeros/farmacologia , Compostos de Amônio Quaternário/farmacologia , RNA Interferente Pequeno/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Células HeLa , Humanos , Modelos Biológicos , Compostos Organofosforados/química , Compostos Organofosforados/metabolismo , Polímeros/química , Polímeros/metabolismo , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Relação Estrutura-Atividade
2.
Mol Pharm ; 9(11): 3012-22, 2012 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-23025592

RESUMO

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH(2)Cl(2) (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.


Assuntos
Administração por Inalação , Anti-Infecciosos/farmacologia , Dextranos/administração & dosagem , Portadores de Fármacos , Metano/análogos & derivados , Nanopartículas/química , Prata/química , Anti-Infecciosos/administração & dosagem , Metano/química , Metano/metabolismo , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Preparações Farmacêuticas/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Prata/metabolismo , Solubilidade , Staphylococcus aureus/efeitos dos fármacos
3.
Curr Top Med Chem ; 15(13): 1236-56, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25858133

RESUMO

The concept of Nanomedicine emerged along with the new millennium, and it is expected to provide solutions to some of modern medicine's unsolved problems. Nanomedicine offers new hopes in several critical areas such as cancer treatment, viral and bacterial infections, medical imaging, tissue regeneration, and theranostics. To explore all these applications, a wide variety of nanomaterials have been developed which include liposomes, dendrimers, nanohydrogels and polymeric, metallic and inorganic nanoparticles. Recently, interlocked systems, namely rotaxanes and catenanes, have been incorporated into some of these chemical platforms in an attempt to improve their performance. This review focus on the nanomedicine applications of nanomaterials containing interlocked structures. The introduction gives an overview on the significance of interdisciplinary science in the progress of the nanomedicine field, and it explains the evolution of interlocked molecules until their application in nanomedicine. The following sections are organized by the type of interlocked structure, and it comprises details of the in vitro and/or in vivo experiments involving each material: rotaxanes as imaging agents, rotaxanes as cytotoxic agents, rotaxanes as peptide transporters, mechanized silica nanoparticles as stimuli responsive drug delivery systems, and polyrotaxanes as drug and gene delivery systems.


Assuntos
Catenanos/química , Diagnóstico por Imagem/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , Rotaxanos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Catenanos/metabolismo , Dendrímeros/síntese química , Dendrímeros/uso terapêutico , Técnicas de Transferência de Genes , Humanos , Hidrogéis/química , Hidrogéis/uso terapêutico , Lipossomos/química , Lipossomos/uso terapêutico , Camundongos , Nanomedicina/instrumentação , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/patologia , Neoplasias/terapia , Regeneração , Rotaxanos/metabolismo , Nanomedicina Teranóstica/métodos
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