Socorro Espuelas

Universidad de Navarra, Iruña, Navarre, Spain

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Publications (49)145.1 Total impact

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    ABSTRACT: Patients affected by cutaneous leishmaniasis need a topical treatment which cures lesions without leaving scars. Lesions are produced not only by the parasite but also by an uncontrolled and persistent inflammatory immune response. In this study, we proposed the loading of β-lapachone (β-LP) in lecithin-chitosan nanoparticles (NP) for targeting the drug to the dermis, where infected macrophages reside, and promote wound healing. The loading of β-LP in NP was critical to achieve important drug accumulation in the dermis and permeation through the skin. In addition, it did not influence the drug antileishmanial activity. When topically applied in L. major infected BALB/c mice, β-LP NP achieved no parasite reduction but they stopped the lesion progression. Immuno-histopathological assays in CL lesions and quantitative mRNA studies in draining lymph nodes confirmed that β-LP exhibited anti-inflammatory activity leading to the down-regulation of IL-1β and COX-2 expression and a decrease of neutrophils infiltrate. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine: nanotechnology, biology, and medicine 08/2015; DOI:10.1016/j.nano.2015.07.011 · 5.98 Impact Factor
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    ABSTRACT: The generation of new antileishmanial drugs has become a priority. Selenium and its derivatives are standing out as having promising leishmanicidal activity. In fact, some parasites express selenoproteins, and metabolize selenium. Recently, selenium derivatives have shown the potential to reduce parasitemia, clinical manifestations and mortality in parasite-infected mice. In this paper, after selecting four candidates according to drug-likeness parameters, we observed that two of them, called 2B: (Methyl N,N' -di(thien-2-ylcarbonyl)-imidoselenocarbamate) and 4B: (Methyl N,N' -di(5-nitrothien-3-ylcarbonyl)-imidoselenocarbamate), exhibit in Leishmania major promastigotes low IC50s (<3μM), good selectivity index (SI>5) and lack toxicity on macrophages. In addition, analyzing their therapeutic potential against L. major in vitro infection, both compounds display a dramatic reduction of amastigote burden (∼ 80%) with sub-lethal concentrations. Furthermore, in macrophages, these selenocompounds induce nitric oxide production, which has been described to be critical for the defence against intracellular pathogens. 2B: and 4B: demonstrated to cause cell cycle arrest in G1. Interestingly, evaluation of gene expression related to proliferation (PCNA), treatment resistance (ABC-transporter and α-tubulin) and virulence (QDPR) showed several alterations in gene expression profiling. All these aforementioned results prompt us to propose both compounds as candidates to treat leishmanial infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 07/2015; 59(9). DOI:10.1128/AAC.00997-15 · 4.45 Impact Factor
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    ABSTRACT: A molecular modeling study has been carried out on two previously reported series of symmetric diselenide derivatives that show remarkable antileishmanial in vitro activity against Leishmania infantum intracellular amastigotes and in infected macrophages (THP-1 cells), in addition to showing favorable selectivity indices. Series 1 consists of compounds that can be considered as central scaffold constructed with a diaryl/dialkylaryl diselenide central nucleus, decorated with different substituents located on the aryl rings. Series 2 consists of compounds constructed over a diaryl diselenide central nucleus, decorated in 4 and 4' positions with an aryl or heteroaryl sulfonamide fragment, thus forming the diselenosulfonamide derivatives. With regard to the diselenosulfonamide derivatives (2 series), the activity can be related, as a first approximation, with (a) the ability to release bis(4-aminophenyl) diselenide, the common fragment which can be ultimately responsible for the activity of the compounds. (b) the anti-parasitic activity achieved by the sulfonamide pharmacophore present in the analyzed derivatives. The data that support this connection include the topography of the molecules, the conformational behavior of the compounds, which influences the bond order, as well as the accessibility of the hydrolysis point, and possibly the hydrophobicity and polarizability of the compounds. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Molecular Graphics and Modelling 06/2015; 60. DOI:10.1016/j.jmgm.2015.06.002 · 2.02 Impact Factor
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    Socorro Espuelas
    Therapeutic delivery 02/2015; 6(2):101-3. DOI:10.4155/tde.14.107
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    ABSTRACT: The aim of the work was to evaluate in vitro and in vivo the effect of the addition of poly(ethylene glycol) (PEG) to paclitaxel (PTX)–cyclodextrin poly(anhydride) nanoparticles. For this, PTX in poly(anhydride) nanoparticles complexed with cyclodextrins (either 2-hydroxypropyl-β-cyclodextrin or β-cyclodextrin) and combined with PEG 2000 were prepared by the solvent displacement method. Intestinal permeability in vitro and in vivo pharmacokinetic studies in C57BL/6J mice were performed. Nanoparticle formulations containing PTX increased its apparent permeability through rat intestine in vitro in the Ussing chambers, enhancing its permeability 10–15 times compared with commercial Taxol®. In addition, in pharmacokinetic studies, drug plasma levels were observed for at least 24 h leading to a relative oral bioavailability between 60% and 80% for PTX complexed with cyclodextrin and loaded in pegylated poly(anhydride) nanoparticles after oral gavage. In all, PTX–cyclodextrin complexes encapsulated in pegylated nanoparticles managed to promote the intestinal uptake of the drug displaying sustained plasma levels after oral administration to laboratory animals with a more prolonged plasma profile compared with the formulation with no PEG at all. Therefore, pegylated poly(anhydride) nanoparticles represent a promising carrier for the oral delivery of PTX. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci
    Journal of Pharmaceutical Sciences 01/2015; DOI:10.1002/jps.24354 · 3.01 Impact Factor
  • Beatriz San Román · Sara Gómez · Juan M Irache · Socorro Espuelas
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    ABSTRACT: Purpose - The objective of this work was to evaluate the effect in the immune response produced by CpG oligodeoxynucleotides (ODN) co-encapsulated with the antigen ovalbumin (OVA) within poly(lactic-co-glycolic) acid (PLGA) 502 and 752 microparticles (MP). MP were prepared by blending 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) with PLGA and Total Recirculation One Machine System (TROMS) technology and contained OVA along with CpG sequences associated to DOTAP. After confirming the integrity of both encapsulated molecules, BALB/c mice were immunized with the resulting MP and OVA-specific antibodies and cytokine production were assessed in order to determine the immunological profile induced in mice. One m near non-charged MP co-encapsulated very efficiently both OVA and CpG ODN. The release of both OVA and CpG was slow and incomplete irrespective of polymer. The results of the immune response induced in BALB/c mice indicated that, depending on the PLGA polymer used, co-encapsulation did not improve the immunogenicity of the antigen, compared either with the simply co-administration of both antigen and CpG, or with the microencapsulated antigen. Thus, mice immunized with OVA associated to PLGA 756 displayed an IgG2a characterized response which was biased to an IgG1 profile in case of CpG co-encapsulation. On the contrary, the co-encapsulation of CpG with OVA into PLGA 502 significantly improved the isotype shifting in comparison with the one showed by mice immunized with OVA loaded PLGA 502. This study underlines the importance of MP characteristics to fully exploit simultaneous antigen and CpG ODN particulate delivery as effective vaccine construct.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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    ABSTRACT: Topical therapy is the ideal outpatient treatment of cutaneous leishmaniasis (CL) because of the ease of administration and lower cost. It could be suitable as monotherapy for localized cutaneous leishmaniasis (LCL) or in combination with systemic therapies for more severe forms of the disease. Although paromomycin (PM) ointment can be recommended for the treatment of LCL caused by L. major, a more effective topical treatment should be achieved regarding the physicochemical properties of this aminoglucoside and its rather poor intrinsic antileishmanial activity, that hampers the accumulation of enough amount of drug in the dermis (where the infected macrophages home) to exert its activity. In this work, we determined a 50% effective dose of 5.6 μM for a novel compound, bis-4-aminophenyldiselenide, against L. major intracellular amastigotes. This compound and PM were formulated in chitosan hydrogels and ex vivo permeation and retention studies in the different skin layers were performed with pig ear skin in Franz diffusion cells. The results showed that less than 2-4% of the diselenide drug penetrated and permeated through the skin. In contrast, the percentage of PM penetration was about 25-60% without important retention in the skin. When topically applied to lesions of L. major infected BALB/c mice, the novel diselenide chitosan formulation was unable to slow lesion progression and reduce parasite burden. Considerations during the process of novel drug development and formulation discovery algorithm for CL are discussed.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 06/2014; 62. DOI:10.1016/j.ejps.2014.06.010 · 3.01 Impact Factor
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    ABSTRACT: Introduction: Cutaneous and mucocutaneous leishmaniasis are major tropical skin diseases. Topical treatment is currently limited to the least severe forms of cutaneous leishmaniasis (CL) without risk of dissemination. It is also recommended in combination with systemic therapy for more severe forms. Progresses in this modality of treatment are hindered by the heterogeneity of the disease and shortcomings in the clinical trials. Areas covered: This review overlooks three major modalities of topical therapies in use or under investigation against CL: chemotherapy, photodynamic therapy and immunotherapy; either with older compounds such as paramomycin or more recent nitric oxide donors, antimicrobial peptides or silver derivatives. The advantages and limitations of their administration with newer formulation strategies such as nanoparticles (NPs) are discussed. Expert opinion: The efficacy of a topical treatment against CL depends not only on the intrinsic antileishmanial activity of the drug but also on the amount of drug available in the dermis. NPs as sustained release systems and permeation enhancers could favour the creation of a drug reservoir in the dermis. Additionally, certain NPs have immunomodulatory properties or wound healing capabilities of benefit in CL treatment. Pending task is the selective delivery of active compounds to intracellular amastigotes, because even small NPs are unable to penetrate deeply into the skin to encounter infected macrophages (except in ulcerative lesions).
    Expert Opinion on Drug Delivery 03/2014; 11(4). DOI:10.1517/17425247.2014.885500 · 4.84 Impact Factor
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    ABSTRACT: Aim: The authors report a novel approach for enhancing the oral absorption of paclitaxel (PTX) by encapsulation in poly(anhydride) nanoparticles (NPs) containing cyclodextrins and poly(ethylene glycol). Materials & methods: Formulations were prepared using the solvent displacement method. Subsequently, pharmacokinetics and organ distribution assays were evaluated after oral administration into C57BL/6J mice. In addition, antitumor efficacy studies were performed in a subcutaneous tumor model of Lewis lung carcinoma. Results: PTX-loaded NPs displayed sizes between 190-300 nm. Oral NPs achieved drug plasma levels for at least 24 h, with an oral bioavailability of 55-80%. Organ distribution studies revealed that PTX, orally administered in NPs, underwent a similar distribution to intravenous Taxol(®) (Bristol-Myers-Squibb, NJ, USA). For in vivo antitumor assays, oral strategy maintained a slower tumor growth than intravenous Taxol. Conclusion: PTX orally administered in poly(anhydride) NPs, combined with cyclodextrins and poly(ethylene glycol), displayed sustained plasma levels and significant antitumor effect in a syngenic tumor model of carcinoma in mice. Original submitted 8 January 2013; Revised submitted 10 October 2013.
    Nanomedicine 01/2014; 9(14). DOI:10.2217/nnm.13.199 · 5.82 Impact Factor
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    ABSTRACT: Diselenide and sulfonamide derivatives have recently attracted considerable interest as leishmanicidal agents in drug discovery. In this study, a novel series of sixteen hybrid selenosulfonamides has been synthesized and screened for their in vitro activity against Leishmania infantum intracellular amastigotes and THP-1 cells. These assays revealed that most of the compounds exhibited antileishmanial activity in the low micromolar range and led us to identify three lead compounds (derivatives 2, 7 and 14) with IC50 values ranging from 0.83 to 1.47 μM and selectivity indexes (SI) over 17, much higher than those observed for the reference drugs miltefosine and edelfosine. When evaluated against intracellular amastigotes, hybrid compound 7 emerged as the most active compound (IC50 = 2.8 μM), showing higher activity and much less toxicity against THP-1 cells than edelfosine. These compounds could potentially serve as templates for future drug-optimization and drug-development efforts for their use as therapeutic agents in developing countries.
    European Journal of Medicinal Chemistry 01/2014; 74C:116-123. DOI:10.1016/j.ejmech.2013.12.030 · 3.43 Impact Factor
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    ABSTRACT: Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez® AN, GZ) and Pluronic® F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histophatological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.
    International Journal of Pharmaceutics 12/2013; 459(1-2). DOI:10.1016/j.ijpharm.2013.11.030 · 3.65 Impact Factor
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    ABSTRACT: We recently demonstrated that immunization with polyester poly (lactide-co-glycolide acid) (PLGA) nanoparticles loaded with the 11 kDa Leishmania vaccine candidate Kinetoplastid Membrane Protein 11 (KMP-11) significantly reduced parasite load in vivo. Presently, we explored the ability of the recombinant PLGA nanoparticles to stimulate innate responses in macrophages and the outcome of infection with L. braziliensis in vitro. Incubation of macrophages with KMP-11-loaded PLGA nanoparticles significantly decreased parasite load. In parallel, we observed augmented production of nitric oxide, superoxide, TNF-α and IL-6. An increased release of CCL2/MCP-1 and CXCL1/KC was also observed, resulting in macrophage and neutrophil recruitment in vitro. Lastly, the incubation of macrophages with KMP-11-loaded PLGA nanoparticles triggered activation of caspase-1 and the secretion of IL-1β and IL-18, suggesting inflammasome participation. Inhibition of caspase-1 significantly increased the parasite load. We conclude that KMP-11-loaded PLGA nanoparticles promote the killing of intracellular Leishmania parasites through the induction of potent innate responses.
    Nanomedicine: nanotechnology, biology, and medicine 04/2013; DOI:10.1016/j.nano.2013.04.003 · 5.98 Impact Factor
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    ABSTRACT: Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.
    Annales Pharmaceutiques Françaises 03/2013; 71(2):109–118. DOI:10.1016/j.pharma.2012.12.005
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    ABSTRACT: Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol(®) administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.
    Annales Pharmaceutiques Françaises 03/2013; 71(2):109-18.
  • S Espuelas · D Plano · P Nguewa · M Font · J A Palop · J M Irache · C Sanmartin
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    ABSTRACT: The protozoan diseases leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease (CD) are responsible for substantial global morbidity and mortality in tropical and subtropical regions. Environmental changes, drug resistance and immunosuppression are contributing to the emergence and spread of these diseases. In the absence of safe and efficient vaccines, chemotherapy, together with vector control, remains the most important measure to control kinetoplastid diseases. Nevertheless, the current chemotherapeutic treatments are clearly inadequate because of their toxic effects, generation of resistances as well as route and schedules of administration not adapted to the field-conditions. This review overlooks the strategies that can be addressed to meet immediately the patient needs such as the reconsideration of current regimens of administration and the rational combination of drugs in use. In the medium-long term, due to new methodologies of medicinal-chemistry, the screening from natural products and the identification of new therapeutic targets, new lead compounds have great chance to advance through the drug development pipeline to clinic. Modern pharmaceutical formulation strategies and nanomedicines also merit a place in view of the benefits of a single dose of liposomal Amphotericin B (AmBisome ®) against visceral leishmaniasis. BBB-targeted nanodevices could be suited for selective delivery of drugs against HAT encephalitic phase. Bioadhesive nanoparticles can be proposed to enhance the bioavailability of drugs after oral administration by reason of improving the drug solubility, and permeability across the intestinal epithelia.
    Current Medicinal Chemistry 07/2012; 19(25):4259-88. DOI:10.2174/092986712802884222 · 3.85 Impact Factor
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    ABSTRACT: Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection.
    International Journal of Nanomedicine 04/2012; 7:2115-27. DOI:10.2147/IJN.S30093 · 4.38 Impact Factor
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    ABSTRACT: The oral route is preferred by patients for drug administration due to its convenience, resulting in improved compliance. Unfortunately, for a number of drugs (e.g., anticancer drugs), this route of administration remains a challenge. Oral chemotherapy may be an attractive option and especially appropriate for chronic treatment of cancer. However, this route of administration is particularly complicated for the administration of anticancer drugs ascribed to Class IV of the Biopharmaceutical Classification System. This group of compounds is characterized by low aqueous solubility and low intestinal permeability. This review focuses on the use of cyclodextrins alone or in combination with bioadhesive nanoparticles for oral delivery of drugs. The state-of-the-art technology and challenges in this area is also discussed.
    Therapeutic delivery 01/2012; 3(1):43-57. DOI:10.4155/tde.11.140
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    ABSTRACT: Nanomedicine can be defined as the application of nanotechnology to the prevention and treatment of diseases as well as for diagnosis purposes. In this context, the development of various types of drug-carrier nanodevices offers new strategies for targeted drug delivery, minimising the secondary effects and the toxicity associated to drug widespread to healthy organs or cells. This review is divided in two different parts. The first one summarizes the main types of nanomedicines developed in the past few decades, including drug nanocrystals, polymer therapeutics, lipid-nanosized and polymeric-nanosized drug delivery systems. The second part of our review is devoted, more specifically, to the presentation of polymeric nanoparticles. Here, we discuss various aspects of nanoparticle formulation, characterization, behaviour in the body and some of their potential applications. More particularly we present some approaches for the treatment of cancer, treatment of infectious diseases and the potential of these nanoparticles as adjuvants for vaccination purposes.
    Veterinary Parasitology 05/2011; 180(1-2):47-71. DOI:10.1016/j.vetpar.2011.05.028 · 2.55 Impact Factor
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    ABSTRACT: INTRODUCTION: The oral administration of drugs belonging to Class IV of the Biopharmaceutical Classification System (BCS) represents a major challenge. These drugs display poor aqueous solubility and specific permeability characteristics. Most of these compounds are substrates of the P-glycoprotein and/or the cytochrome P450. Among other types of drug, various anti-cancer drugs also suffer from these drawbacks (i.e., paclitaxel), which limits the possibilities for developing oral treatments. AREAS COVERED: This review discusses the factors that influence the bioavailability of drugs when administered by the oral route, as well as the capabilities of cyclodextrins when associated with nanoparticles. In particular, evidence is given regarding the synergistic effect between cyclodextrins and bioadhesive nanoparticles, on the oral delivery of pharmaceuticals. EXPERT OPINION: This article aims to provide an overview of the multiple gains in incorporating cyclodextrins in poly(anhydride) nanoparticles, including improvement of their bioadhesive capability, the loading of lipophilic drugs and the effect on efflux membrane proteins and cytochrome P450. The combination between bioadhesive nanoparticles and P-gp inhibitors without pharmacological activity (i.e., cyclodextrins) may be useful to promote the oral bioavailability of drugs ascribed to Class IV of the BCS.
    Expert Opinion on Drug Delivery 04/2011; 8(6):721-34. DOI:10.1517/17425247.2011.572069 · 4.84 Impact Factor
  • Socorro Espuelas · Maite Agüeros · Irene Esparza · Juan M. Irache
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    ABSTRACT: Oral delivery remains the preferred route for drug administration thanks to its patient convenience and compliance. However, many anticancer drugs are unsuitable for oral formulations. This chapter describes the major obstacles to cancer drugs gastrointestinal absorption (namely low solubility, poor membrane permeability or extensive pre-systemic metabolism) and strategies to circumvent them, with special attention to nanocarriers. Until now we have proved an enhancement in the oral bioavailability of entrapped anticancer drugs. The remaining challenge is designing nanoparticles able to specifically target the drugs to tumor cells anywhere in the body after oral administration. To this aim, it will be necessary more studies clarifying the correlation between nanoparticles properties and their interaction with the gut mucosa, their transport through and their final outcome. The possibilities of oral administration of other modalities of cancer treatment, as immunotherapy, are also discussed. KeywordsCancer therapy-Oral administration-Bioavailability-Nanocarriers-Cancer immunotherapy-P-gp
    12/2010: pages 487-509;

Publication Stats

696 Citations
145.10 Total Impact Points

Institutions

  • 2004–2015
    • Universidad de Navarra
      • • Department of Pharmacy and Pharmaceutical Technology
      • • Department of Organic and Pharmaceutical Chemistry
      • • School of Pharmacy
      • • Department of Microbiology and Parasitology
      Iruña, Navarre, Spain
  • 2005–2006
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France