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1.
Pharm Res ; 31(11): 2975-87, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24805278

RESUMO

PURPOSE: In general, the surface functionalization of polymeric nanoparticles is carried out by covalently bounding ligands to the nanoparticle surface. This process can cause a lack or decrease of the ligand specificity to its target receptor, besides the need of purification steps. We proposed a ligand-metal-chitosan-lecithin complex as a new strategy to functionalize the surface of biodegradable nanoparticles. METHODS: One pot synthesis of scFv anti-LDL(-)-functionalized nanocapsules was carried out by self-assembly and interfacial reactions. Particle sizing techniques, lipid peroxidation and molecular recognition by enzyme linked immuno sorbent assays were carried out. RESULTS: The selected formulation had unimodal size distribution with mean diameter of about 130 nm. The metals in the complex did not enhance the oxidative stress, and the scFv anti-LDL(-)-functionalized nanocapsules recognized LDL(-) and did not react with native LDL indicating the maintenance of the active site of the fragment. CONCLUSIONS: The one pot synthesis, using the ligand-metal-chitosan-lecithin complex to functionalize the surface of the biodegradable nanocapsules, maintained the active site of the antibody fragment making the device interesting for applications in nanomedicine.


Assuntos
Lipoproteínas LDL/imunologia , Nanocápsulas/química , Nanopartículas/química , Polímeros/química , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/imunologia , Domínio Catalítico , Química Farmacêutica/métodos , Quitosana/química , Lecitinas/química , Ligantes , Peroxidação de Lipídeos/efeitos dos fármacos , Metais/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula
2.
Int J Pharm ; 426(1-2): 271-279, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22322210

RESUMO

The hemocompatibility of nanoparticles is of critical importance for their systemic administration as drug delivery systems. Formulations of lipid-core nanocapsules, stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan (LNC and LNC-CS), were prepared and characterized by laser diffraction (D[4,3]: 129 and 134 nm), dynamic light scattering (119 nm and 133 nm), nanoparticle tracking (D50: 124 and 139 nm) and particle mobility (zeta potential: -15.1 mV and +9.3 mV) analysis. In vitro hemocompatibility studies were carried out with mixtures of nanocapsule suspensions in human blood at 2% and 10% (v/v). The prothrombin time showed no significant change independently of the nanocapsule surface potential or its concentration in plasma. Regarding the activated partial thromboplastin time, both suspensions at 2% (v/v) in plasma did not influence the clotting time. Even though suspensions at 10% (v/v) in plasma decreased the clotting times (p<0.05), the values were within the normal range. The ability of plasma to activate the coagulation system was maintained after the addition of the formulations. Suspensions at 2% (v/v) in blood showed no significant hemolysis or platelet aggregation. In conclusion, the lipid-core nanocapsules uncoated or coated with chitosan are hemocompatible representing a potential innovative nanotechnological formulation for intravenous administration.


Assuntos
Materiais Biocompatíveis , Quitosana/toxicidade , Portadores de Fármacos , Lecitinas/toxicidade , Lipídeos/toxicidade , Nanocápsulas , Poliésteres/toxicidade , Polissorbatos/toxicidade , Coagulação Sanguínea/efeitos dos fármacos , Química Farmacêutica , Quitosana/química , Composição de Medicamentos , Membrana Eritrocítica/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Lecitinas/química , Luz , Lipídeos/química , Teste de Materiais , Nanotecnologia , Tempo de Tromboplastina Parcial , Tamanho da Partícula , Agregação Plaquetária/efeitos dos fármacos , Poliésteres/química , Polissorbatos/química , Tempo de Protrombina , Espalhamento de Radiação , Tecnologia Farmacêutica/métodos
3.
Nanoscale Res Lett ; 7(1): 251, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22587614

RESUMO

The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% (w/v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.

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