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1.
Langmuir ; 34(23): 6874-6886, 2018 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-29776311

RESUMO

The success of nanoparticulate formulations in drug delivery depends on various aspects including their toxicity, internalization, and intracellular location. Vesicular assemblies consisting of phospholipids and amphiphilic block copolymers are an emerging platform, which combines the benefits from liposomes and polymersomes while overcoming their challenges. We report the synthesis of poly(cholesteryl methacrylate)- block-poly(2-(dimethylamino) ethyl methacrylate) (pCMA- b-pDMAEMA) block copolymers and their assembly with phospholipids into hybrid vesicles. Their geometry, their ζ-potential, and their ability to adsorb onto polymer-coated surfaces were assessed. Giant unilamellar vesicles were employed to confirm the presence of both the phospholipids and the block copolymer in the same membrane. Furthermore, the cytotoxicity of selected hybrid vesicles was determined in RAW 264.7 mouse macrophages, primary rat Kupffer cells, and human macrophages. The internalization and lysosomal escape ability of the hybrid vesicles were confirmed using RAW 264.7 mouse macrophages. Taken together, our findings illustrate that the reported hybrid vesicles are a promising complementary drug delivery platform for existing liposomes and polymersomes.


Assuntos
Sistemas de Liberação de Medicamentos , Polímeros/administração & dosagem , Lipossomas Unilamelares/administração & dosagem , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Fosfolipídeos/química , Polímeros/química , Polímeros/metabolismo , Ratos , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismo , Lipossomas Unilamelares/toxicidade
3.
Colloids Surf B Biointerfaces ; 111: 609-17, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23907049

RESUMO

Concentrated and interconnected penetration enhancer containing vesicles (PEVs) are proposed as carriers for dermal delivery of diclofenac. PEVs were prepared by using a commercial phosphatidylcholine mixture (180 mg/m) and transcutol in different amounts. Conventional liposomes were also prepared and tested as control. All vesicles showed a mean size ranging from 75 to 253 nm with fairly narrow size distribution, negative zeta potential value, and drug loading capacity between 48 and 70%. SWAXS studies showed that composition affected vesicle structure and morphology: 10 and 30% transcutol PEVs were unilamellar while liposomes and 20% transcutol PEVs were multilamellar. Rheological studies demonstrated that control liposomes and 10 and 30% transcutol containing PEVs behaved as Newtonian fluids while 20% transcutol containing PEVs showed a plastic behavior. Ex vivo (trans)dermal delivery experiments showed an improved skin deposition of diclofenac when PEVs were used. Vesicle toxicity and uptake of fibroblasts, target of inflammation treatment, were evaluated by MTT test and fluorescence microscopy. Control liposomes and PEVs were both able to interact and being internalized by the 3T3 fibroblasts at all time exposure tested. Furthermore, PEVs showed to be able to reduce the in vitro drug toxicity.


Assuntos
Diclofenaco/farmacologia , Sistemas de Liberação de Medicamentos , Fibroblastos/citologia , Pele/efeitos dos fármacos , Lipossomas Unilamelares/química , Células 3T3 , Animais , Morte Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fluoresceínas/metabolismo , Fluorescência , Técnicas In Vitro , Camundongos , Coloração Negativa , Tamanho da Partícula , Permeabilidade/efeitos dos fármacos , Fosfatidiletanolaminas/metabolismo , Reologia/efeitos dos fármacos , Rodaminas/metabolismo , Espalhamento a Baixo Ângulo , Sus scrofa , Lipossomas Unilamelares/toxicidade , Difração de Raios X
4.
Biotechnol Lett ; 29(11): 1637-44, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17636387

RESUMO

Small unilamellar vesicles associated with plasmid DNA showed maximum association efficiency for a cationic mixture of egg phosphatidylcholine (EPC):1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE):di-1,2-dioleoyl-3-trimethyl ammonium propane (DOTAP) (16:8:1 molar ratio) [65%], followed by neutral lipids EPC:1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE):cholesterol (Chol) (2:2:1 molar ratio) [30%], and a polymerized formulation 1,2-bis(10,12-tricosadiynoyl)sn-glycero-3-phosphocholine (DC8,9PC):DMPE:Chol (2:2:1 molar ratio) [11%]. The hydrophobicity factor (HF) for these formulations followed the trend DC8,9PC:DMPE:CHOL < EPC:DMPE:Chol < EPC:DOPE DOTAP, and DNA association did not alter this trend. Results suggest that the higher the HF value, the more fluid the membrane and the higher the efficiency of DNA association. On the other hand, no differences were observed in cell toxicity with lipids up to 1 mg/ml in VERO cells.


Assuntos
DNA/genética , Técnicas de Transferência de Genes , Plasmídeos/genética , Lipossomas Unilamelares , Animais , Sobrevivência Celular , Chlorocebus aethiops , Interações Hidrofóbicas e Hidrofílicas , Lipossomas Unilamelares/síntese química , Lipossomas Unilamelares/toxicidade , Células Vero
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