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1.
Eur J Pharm Biopharm ; 69(1): 83-93, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18166446

RESUMEN

Chitosan/tripolyphosphate nanoparticles have already been demonstrated to promote peptide absorption through several mucosal surfaces. We have recently developed a new drug delivery system consisting of complexes formed between preformed chitosan/tripolyphosphate nanoparticles and phospholipids, named as lipid/chitosan nanoparticles (L/CS-NP) complexes. The aim of this work was to microencapsulate these protein-loaded L/CS-NP complexes by spray-drying, using mannitol as excipient to produce microspheres with adequate properties for pulmonary delivery. Results show that the obtained microspheres are spherical and present appropriate aerodynamic characteristics for lung delivery (aerodynamic diameters around 2-3 microm and low apparent tap density of 0.4-0.5 g/cm3). The physicochemical properties of the L/CS-NP complexes are affected by the phospholipids composition. Phospholipids provide a controlled release of the encapsulated protein (insulin), which was successfully associated to the system (68%). The complexes can be easily recovered from the mannitol microspheres upon incubation in aqueous medium, maintaining their morphology and physicochemical characteristics. Therefore, this work demonstrates that protein-loaded L/CS-NP complexes can be efficiently microencapsulated, resulting in microspheres with adequate properties to provide a deep inhalation pattern. Furthermore, they are expected to release their payload (the complexes and, consequently, the encapsulated macromolecule) after contacting with the lung aqueous environment.


Asunto(s)
Quitosano/química , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Lípidos/química , Pulmón/efectos de los fármacos , Microesferas , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Insulina/química , Microscopía Electrónica de Rastreo , Nanopartículas/química , Polifosfatos/química , Polvos , Tecnología Farmacéutica/métodos
2.
Biomaterials ; 28(8): 1553-64, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17169422

RESUMEN

This study evaluated in vitro and in vivo a colloidal nanosystem with the potential to deliver drugs to the ocular surface. This nanosystem, liposome-chitosan nanoparticle complexes (LCS-NP), was created as a complex between liposomes and chitosan nanoparticles (CS-NP). The conjunctival epithelial cell line IOBA-NHC was exposed to several concentrations of three different LCS-NP complex to determine the cytotoxicity. The uptake of LCS-NP by the IOBA-NHC conjunctival cell line and by primary cultured conjunctival epithelial cells was examined by confocal microscopy. Eyeball and lid tissues from LCS-NP-treated rabbits were evaluated for the in vivo uptake and acute tolerance of the nanosystems. The in vitro toxicity of LCS-NP in the IOBA-NHC cells was very low. LCS-NPs were identified inside IOBA-NHC cells after 15 min and inside primary cultures of conjunctival epithelial cells after 30 min. Distribution within the cells had different patterns depending on the LCS-NP formulation. Fluorescence microscopy of the conjunctiva revealed strong cellular uptake of LCS-NP in vivo and less intensive uptake by the corneal epithelium. No alteration was macroscopically observed in vivo after ocular surface exposure to LCS-NP. Taken together, these data demonstrate that LCS-NPs are potentially useful as drug carriers for the ocular surface.


Asunto(s)
Materiales Biocompatibles , Quitosano , Sistemas de Liberación de Medicamentos , Ojo , Nanopartículas , Línea Celular Transformada , Humanos , Liposomas
3.
Curr Top Med Chem ; 14(9): 1161-71, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24678706

RESUMEN

Cationic nanoemulsions have been recently considered as potential delivery systems for oligonucleotides (ON) targeting Plasmodium falciparum topoisomerase II gene. This study is aiming to select the best composition of nanoemulsions intended to ON adsorption by means of a 2(3) full factorial design. Based on their physicochemical properties, two formulations were selected for further studies, both composed by medium chain triglycerides, egg-lecithin, and either oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Adsorption isotherms of phosphodiester or phosphorothioate ON on the optimized nanoemulsions were obtained (ultrafiltration/centrifugation procedure). They showed a significant higher amount of ON adsorbed on DOTAP nanoemulsion when compared to the OA ones. The Langmuir adsorption model provides the most satisfactory representation of the adsorption data. Evidence of ON adsorption could be detected by the inversion of the ζ-potential and the morphology of the oil droplets examined by transmission electron microscopy. Preliminary results regarding hemolytic effect and P. falciparum survival after exposure to optimized formulations were related to their physicochemical properties and in vitro effects. The overall results showed the potential of the optimized nanoemulsions as non-viral carriers for antisense ON against malaria parasites.


Asunto(s)
ADN-Topoisomerasas de Tipo II/metabolismo , Diseño de Fármacos , Nanoestructuras/química , Oligonucleótidos Antisentido/química , Oligonucleótidos Antisentido/farmacología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Adsorción , Cationes/química , Cationes/metabolismo , Emulsiones , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Eritrocitos/microbiología , Microscopía Electrónica de Transmisión , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/metabolismo , Propiedades de Superficie
4.
Methods Enzymol ; 465: 289-312, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19913173

RESUMEN

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.


Asunto(s)
Quitosano/administración & dosificación , Liposomas , Membrana Mucosa , Nanopartículas , Línea Celular , Liofilización , Humanos , Espectrometría de Masas , Espectrofotometría Ultravioleta , Propiedades de Superficie , Agua/química
5.
Pharm Res ; 21(5): 803-10, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15180338

RESUMEN

PURPOSE: To assess the potential of chitosan (CS) nanoparticles for ocular drug delivery by investigating their interaction with the ocular mucosa in vivo and also their toxicity in conjunctival cell cultures. METHODS: Fluorescent (CS-fl) nanoparticles were prepared by ionotropic gelation. The stability of the particles in the presence of lysozyme was investigated by determining the size and their interaction with mucin, by measuring the viscosity of the mucin dispersion. The in vivo interaction of CS-fl nanoparticles with the rabbit cornea and conjunctiva was analyzed by spectrofluorimetry and confocal microscopy. Their potential toxicity was assessed in a human conjunctival cell line by determining cell survival and viability. RESULTS: CS-fl nanoparticles were stable upon incubation with lysozyme and did not affect the viscosity of a mucin dispersion. In vivo studies showed that the amounts of CS-fl in cornea and conjunctiva were significantly higher for CS-fl nanoparticles than for a control CS-fl solution, these amounts being fairly constant for up to 24 h. Confocal studies suggest that nanoparticles penetrate into the corneal and conjunctival epithelia. Cell survival at 24 h after incubation with CS nanoparticles was high and the viability of the recovered cells was near 100%. CONCLUSIONS: CS nanoparticles are promising vehicles for ocular drug delivery.


Asunto(s)
Quitosano/toxicidad , Sistemas de Liberación de Medicamentos , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Fenómenos Químicos , Química Física , Quitosano/química , Córnea/efectos de los fármacos , Córnea/metabolismo , Estabilidad de Medicamentos , Fluoresceína , Masculino , Microscopía Confocal , Microscopía Electrónica de Rastreo , Microesferas , Mucinas/química , Mucinas/metabolismo , Muramidasa/química , Muramidasa/metabolismo , Conejos
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