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Dive into the research topics where Ana del Pozo-Rodríguez is active.

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Featured researches published by Ana del Pozo-Rodríguez.


Journal of Controlled Release | 2013

Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier

Ana Beloqui Garcia; María Ángeles Solinís; Alicia Rodríguez Gascón; Ana del Pozo-Rodríguez; Anne des Rieux; Véronique Préat

The aims of this work were (i) to evaluate the potential of nanostructured lipid carriers (NLCs) as a tool to enhance the oral bioavailability of poorly soluble compounds using saquinavir (SQV), a BCS class IV drug and P-gp substrate as a model drug, and (ii) to study NLC transport mechanisms across the intestinal barrier. Three different NLC formulations were evaluated. SQV transport across Caco-2 monolayers was enhanced up to 3.5-fold by NLCs compared to SQV suspension. M cells did not enhance the transport of NLCs loaded with SQV. The size and amount of surfactant in the NLCs influenced SQVs permeability, the transcytosis pathway and the efflux of SQV by P-gp. An NLC of size 247 nm and 1.5% (w/v) surfactant content circumvented P-gp efflux and used both caveolae- and clathrin-mediated transcytosis, in contrast to the other NLC formulations, which used only caveolae-mediated transcytosis. By modifying critical physicochemical parameters of the NLC formulation, we were thus able to overcome the P-gp drug efflux and alter the transcytosis mechanism of the nanoparticles. These findings support the use of NLCs approaches for oral delivery of poorly water-soluble P-gp substrates.


European Journal of Pharmaceutics and Biopharmaceutics | 2011

Understanding the mechanism of protamine in solid lipid nanoparticle-based lipofection: The importance of the entry pathway

Diego Delgado; Ana del Pozo-Rodríguez; María Ángeles Solinís; Alicia Rodríguez-Gascón

The aim of our study was to evaluate the effect of protamine on the transfection capacity of solid lipid nanoparticles (SLNs) by correlating it to the internalization mechanisms and intracellular trafficking of the vectors. Vectors were prepared with SLN, DNA, and protamine. ARPE-19 and HEK-293 cells were used for the evaluation of the formulations. Protamine induced a 6-fold increase in the transfection of SLNs in retinal cells due to the presence of nuclear localization signals (NLS), its protection capacity, and a shift in the internalization mechanism from caveolae/raft-mediated to clathrin-mediated endocytosis. However, protamine produced an almost complete inhibition of transfection in HEK-293 cells. In spite of the high DNA condensation capacity of protamine and its content in NLS, this does not always lead to an improvement in cell transfection since it may impair some of the limiting steps of the transfection processes.


International Journal of Pharmaceutics | 2014

A novel gene therapy vector based on hyaluronic acid and solid lipid nanoparticles for ocular diseases

Paola Stephanie Apaolaza; Diego Delgado; Ana del Pozo-Rodríguez; Alicia Rodríguez Gascón; M. Angeles Solinís

The introduction of therapeutic genes in target tissues is considered as a novel tool for the treatment of several diseases. We have developed nanoparticles consisting on SLNs, protamine (P) and hyaluronic acid (HA) as carrier for gene therapy. Stable complexes positively charged and with a particle size ranging from 240 nm to 340 nm were obtained. Transfection studies in ARPE-19 and HEK-293 cells showed the versatility of vectors to efficiently transfect cells with different division rate, widening the potential applications of SLN-based vectors. In ARPE 19cells, the incorporation of P and HA induced almost a 7-fold increase in the transfection capacity of SLNs. The CD44 inhibition studies suggested the participation of this receptor in the internalization of the vectors in this cell line. The intracellular disposition of DNA showed that the HA is able to modulate the high degree of condensation of DNA due to the protamine inside the cells; an important fact, if the vector is uptaken via non-degradative endocytosis. Besides, the therapeutic plasmid which encodes the protein retinoschisin was employed achieving a positive transfection in ARPE-19 cells, showing a promising application of this new non-viral system for the treatment of X-linked juvenile retinoschisis by gene therapy.


International Journal of Pharmaceutics | 2012

Dextran-protamine-solid lipid nanoparticles as a non-viral vector for gene therapy: in vitro characterization and in vivo transfection after intravenous administration to mice.

Diego Delgado; Alicia Rodríguez Gascón; Ana del Pozo-Rodríguez; Enrique Echevarría; Aritz Perez Ruiz de Garibay; Juan Manuel Rodríguez; María Ángeles Solinís

The aim of present work is to evaluate the transfection capacity of a new multicomponent system based on dextran (Dex), protamine (Prot), and solid lipid nanoparticles (SLN) after intravenous administration to mice. The vectors containing the pCMS-EGFP plasmid were characterized in terms of particle size and surface charge. In vitro transfection capacity and cell viability were studied in four cell lines, and compared with the transfection capacity of SLN without dextran and protamine. Transfection capacity was related to the endocytosis mechanism: caveolae or clathrin. The Dex-Prot-DNA-SLN vector showed a higher transfection capacity in those cells with a high ratio of activity of clathrin/caveolae-mediated endocytosis. However, the complex prepared without dextran and protamine (DNA-SLN) was more effective in those cells with a high ratio of activity of caveolae/clathrin-mediated endocytosis. The interaction with erythrocytes and the potential hemolytic effect were also checked. The Dex-Prot-DNA-SLN vector showed no agglutination of erythrocytes, probably due to the presence of dextran. After intravenous administration to BALB/c mice, the vector was able to induce the expression of the green fluorescent protein in liver, spleen and lungs, and the protein expression was maintained for at least 7 days. Although additional studies are necessary, this work reveals the promising potential of this new gene delivery system for the treatment of genetic and non-genetic diseases through gene therapy.


Journal of Ocular Pharmacology and Therapeutics | 2013

Lipid Nanoparticles as Drug/Gene Delivery Systems to the Retina

Ana del Pozo-Rodríguez; Diego Delgado; Alicia Rodríguez Gascón; María Ángeles Solinís

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patients vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.


Human Gene Therapy | 2012

Dextran and Protamine-Based Solid Lipid Nanoparticles as Potential Vectors for the Treatment of X-Linked Juvenile Retinoschisis

Diego Delgado; Ana del Pozo-Rodríguez; María Ángeles Solinís; Marcelino Avilés-Triqueros; Bernhard H. F. Weber; Eduardo Fernández; Alicia Rodríguez Gascón

The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.


European Journal of Pharmaceutics and Biopharmaceutics | 2015

Treatment of ocular disorders by gene therapy

M. Angeles Solinís; Ana del Pozo-Rodríguez; Paola Stephanie Apaolaza; Alicia Rodríguez-Gascón

Gene therapy to treat ocular disorders is still starting, and current therapies are primarily experimental, with most human clinical trials still in research state, although beginning to show encouraging results. Currently 33 clinical trials have been approved, are in progress, or have been completed. The most promising results have been obtained in clinical trials of ocular gene therapy for Leber Congenital Amaurosis, which have prompted the study of several ocular diseases that are good candidates to be treated with gene therapy: glaucoma, age-related macular degeneration, retinitis pigmentosa, or choroideremia. The success of gene therapy relies on the efficient delivery of the genetic material to target cells, achieving optimum long-term gene expression. Although viral vectors have been widely used, their potential risk associated mainly with immunogenicity and mutagenesis has promoted the design of non-viral vectors. In this review, the main administration routes and the most studied delivery systems, viral and non-viral, for ocular gene therapy are presented. The primary ocular disease candidates to be treated with gene therapy have been also reviewed, including the genetic basis and the most relevant preclinical and clinical studies.


BioMed Research International | 2014

Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

Josune Torrecilla; Alicia Rodríguez-Gascón; María Ángeles Solinís; Ana del Pozo-Rodríguez

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.


International Journal of Nanomedicine | 2014

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Alicia Rodríguez-Gascón; Ana del Pozo-Rodríguez; María Ángeles Solinís

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.


Recent Patents on Drug Delivery & Formulation | 2011

Lipid Nanoparticles as Vehicles for Macromolecules: Nucleic Acids and Peptides

Ana del Pozo-Rodríguez; Diego Delgado; María Ángeles Solinís; Alicia Rodríguez Gascón

Traditional drug delivery systems are not efficient for peptide, protein and nucleic acid (plasmid DNA, oligonucleotides or short interfering RNA) delivery, thereby LNP have been exploited as potential delivery and targeting systems of these molecules. Since their discovery in the early 90s several research groups have focused their efforts on the improvement of this kind of nanocarriers in terms of effectiveness and safety. This review features the recent and most relevant patents related to these topics, with particular attention to targeting and protection from environmental agents. Moreover, in the case of nucleic acids strategies to improve transfection mediated by lipid nanoparticles (entrance to the cells, intracellular distribution or going through nuclear envelope) will be assessed. Regarding peptides and proteins, enhancement of encapsulation efficiency and absorption through mucoses are the main studied drawbacks. Finally, this work also includes a summary of the existing patents about the use of LNP as immune response adjuvants by using either plasmid DNA or proteins.

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Dive into the Ana del Pozo-Rodríguez's collaboration.

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María Ángeles Solinís

University of the Basque Country

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Alicia Rodríguez-Gascón

University of the Basque Country

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Alicia Rodríguez Gascón

University of the Basque Country

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Josune Torrecilla

University of the Basque Country

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Diego Delgado

University of the Basque Country

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Paola Stephanie Apaolaza

University of the Basque Country

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M. Angeles Solinís

University of the Basque Country

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Diego Delgado

University of the Basque Country

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Arantxazu Isla

University of the Basque Country

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Mónica Vicente-Pascual

University of the Basque Country

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