Ana C. Calpena
University of Barcelona
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Featured researches published by Ana C. Calpena.
European Journal of Pharmaceutical Sciences | 2003
Elvira Escribano; Ana C. Calpena; Josep Queralt; Rossend Obach; J. Domenech
The aim of this study was to improve the transdermal permeation of sodium diclofenac. Permeation studies were carried out in vitro using human skin (0.4 mm thick) from plastic surgery as a membrane. Four liquid formulations of 1% (w/w) sodium diclofenac were assayed: three ternary solvent systems (M4, M5, M6) and one microemulsion (M3). A 1% (w/w) solution of sodium diclofenac and a commercially available semisolid preparation were tested as reference formulations. The following permeation parameters for diclofenac were assessed: permeability coefficient, flux and drug permeated and retained in the skin at 24 h. The highest values of these parameters were obtained with formula M4, which contains transcutol 59.2%, oleic acid 14.9% and d-limonene 5% (w/w) as permeation enhancers. The anti-inflammatory activity of this formula was compared with that of the semisolid preparation on carrageenan-induced paw edema in rats. As expected from in vitro results, the M4 diclofenac delivery system showed higher activity than the semisolid preparation, both when applied locally (to the inflammation area) and when applied systemically (to the back). Neither treatment irritated the skin when tested on rabbits in a 72-h trial. These results suggest that topical delivery of sodium diclofenac with an absorption enhancer such as a mixture of oleic acid and d-limonene (M4) may be an effective medication for both dermal and subdermal injuries.
Nanotechnology | 2011
E. González-Mira; M.A. Egea; Eliana B. Souto; Ana C. Calpena; María L. García
The purpose of this study was to design and optimize a new topical delivery system for ocular administration of flurbiprofen (FB), based on lipid nanoparticles. These particles, called nanostructured lipid carriers (NLC), were composed of a fatty acid (stearic acid (SA)) as the solid lipid and a mixture of Miglyol(®) 812 and castor oil (CO) as the liquid lipids, prepared by the hot high pressure homogenization method. After selecting the critical variables influencing the physicochemical characteristics of the NLC (the liquid lipid (i.e. oil) concentration with respect to the total lipid (cOil/L (wt%)), the surfactant and the flurbiprofen concentration, on particle size, polydispersity index and encapsulation efficiency), a three-factor five-level central rotatable composite design was employed to plan and perform the experiments. Morphological examination, crystallinity and stability studies were also performed to accomplish the optimization study. The results showed that increasing cOil/L (wt%) was followed by an enhanced tendency to produce smaller particles, but the liquid to solid lipid proportion should not exceed 30 wt% due to destabilization problems. Therefore, a 70:30 ratio of SA to oil (miglyol + CO) was selected to develop an optimal NLC formulation. The smaller particles obtained when increasing surfactant concentration led to the selection of 3.2 wt% of Tween(®) 80 (non-ionic surfactant). The positive effect of the increase in FB concentration on the encapsulation efficiency (EE) and its total solubilization in the lipid matrix led to the selection of 0.25 wt% of FB in the formulation. The optimal NLC showed an appropriate average size for ophthalmic administration (228.3 nm) with a narrow size distribution (0.156), negatively charged surface (-33.3 mV) and high EE (∼90%). The in vitro experiments proved that sustained release FB was achieved using NLC as drug carriers. Optimal NLC formulation did not show toxicity on ocular tissues.
International Journal of Nanomedicine | 2012
Estefanía Vega; M. Antonia Egea; Ana C. Calpena; Marta Espina; M. Luisa García
Poly(D,L-lactide-co-glycolide) and poly(D,L-lactide-co-glycolide) with poly(ethylene glycol) nanospheres (NSs) incorporating flurbiprofen (FB) were freeze-dried with several cryoprotective agents and sterilized by γ-irradiation. Only when 5.0% (w/v) hydroxypropyl-β-cyclodextrin (HPβCD) was used, a complete resuspension by manual shaking and almost identical particle size of the NSs was obtained after freeze-drying. In vitro drug release and ex vivo corneal permeation of NSs with and without HPβCD were evaluated. The presence of HPβCD resulted in a reduction of burst effect, providing a more sustained release of the drug. A significant decrease in the FB transcorneal permeation of NSs containing HPβCD was obtained, related to the slower diffusion of FB observed in the in vitro results. The uptake mechanism of the NSs was examined by confocal microscopy, suggesting that NSs penetrate corneal epithelium through a transcellular pathway. Ocular tolerance was assessed in vitro and in vivo by the Eytex™ and Draize test, respectively. Long-term stability studies revealed that γ-irradiated NSs stored as freeze-dried powders maintained their initial characteristics. Stability studies of the resuspended NSs after 3 months of storage in the aqueous form showed that NSs were stable at 4°C, while formulations stored at 25°C and 40°C increased their initial particle size.
Journal of Pharmaceutical Sciences | 2011
E. González-Mira; S. Nikolić; M.L. García; M.A. Egea; Eliana B. Souto; Ana C. Calpena
The potential use of nanostructured lipid carriers (NLC) composed of a fatty acid [stearic acid (SA)] or a triglyceride (glyceryl behenate) as solid lipids, and a mixture of medium chain triglycerides and castor oil as liquid lipids, for skin administration of flurbiprofen (FB), has been explored. Two different optimized NLC formulations (FB-SANLC based on SA vs. FB-C888NLC based on glyceryl behenate), with respect to the morphometrical properties (particle size and polydispersity index) and the entrapment efficiency, were used in this study. The ex vivo permeation profiles of FB-C888NLC, FB-SANLC and conventional FB solution were evaluated using human skin. An improved FB permeation was observed when the drug was delivered by skin application of FB-C888NLC, attributed to the particle size and matrix crystallinity. The differential scanning calorimetry and X-ray diffraction studies suggested major polymorphic transitions in the lipid matrix of FB-C888NLC. A good correlation between polymorphic transitions and increased drug permeation was observed. However, both NLC dispersions showed a penetration-enhancing ratio (ER) higher than conventional FB solution. The in vitro and in vivo irritancy and local tolerability were assessed by running, respectively, the SKINTEX™ and Draize test. Both FB-C888NLC and FB-SANLC were classified as nonirritant.
International Journal of Pharmaceutics | 2014
Tatiana Andreani; Ana Luiza Ribeiro de Souza; Charlene Priscila Kiill; Esteban N. Lorenzón; Joana F. Fangueiro; Ana C. Calpena; Marco V. Chaud; Maria L. Garcia; Maria Palmira Daflon Gremião; Amélia M. Silva; Eliana B. Souto
The present study reports the production and characterization of PEG-coated silica nanoparticles (SiNP-PEG) containing insulin for oral administration. High (PEG 20,000) and low (PEG 6000) PEG molecular weights were used in the preparations. SiNP were produced by sol-gel technology followed by PEG adsorption and characterized for in vitro release by Franz diffusion cells. In vitro permeation profile was assessed using everted rat intestine. HPLC method has been validated for the determination of insulin released and permeated. Insulin secondary structure was performed by circular dichroism (CD). Uncoated SiNP allowed slower insulin release in comparison to SiNP-PEG. The coating with high molecular weight PEG did not significantly (p> 0.05) alter insulin release. The slow insulin release is attributed to the affinity of insulin for silanol groups at silica surface. Drug release followed second order kinetics for uncoated and SiNP-PEG at pH 2.0. On the other hand, at pH 6.8, the best fitting was first-order for SiNP-PEG, except for SiNP which showed a Boltzmann behavior. Comparing the values of half-live, SiNP-PEG 20,000 showed a faster diffusion followed by Si-PEG 6000 and SiNP. CD studies showed no conformational changes occurring after protein release from the nanoparticles under gastrointestinal simulated conditions.
International Journal of Molecular Sciences | 2015
Aroha Sánchez; Ana C. Calpena; Beatriz Clares
Oxygen is used by eukaryotic cells for metabolic transformations and energy production in mitochondria. Under physiological conditions, there is a constant endogenous production of intermediates of reactive oxygen (ROI) and nitrogen species (RNI) that interact as signaling molecules in physiological mechanisms. When these species are not eliminated by antioxidants or are produced in excess, oxidative stress arises. Oxidative stress can damage proteins, lipids, DNA, and organelles. It is a process directly linked to inflammation; in fact, inflammatory cells secrete a large number of cytokines and chemokines responsible for the production of ROI and RNI in phagocytic and nonphagocytic cells through the activation of protein kinases signaling. Currently, there is a wide variety of diseases capable of producing inflammatory manifestations. While, in the short term, most of these diseases are not fatal they have a major impact on life quality. Since there is a direct relationship between chronic inflammation and many emerging disorders like cancer, oral diseases, kidney diseases, fibromyalgia, gastrointestinal chronic diseases or rheumatics diseases, the aim of this review is to describe the use and role of melatonin, a hormone secreted by the pineal gland, that works directly and indirectly as a free radical scavenger, like a potent antioxidant.
Journal of Materials Chemistry B | 2014
Mafalda Rodrigues; Ana C. Calpena; David B. Amabilino; María Luisa Garduño-Ramírez; Lluïsa Pérez-García
A novel physical gel was obtained using a gemini imidazolium-based amphiphilic molecule dissolved in ethanol-water mixtures. The structure of the gel is comprised of intertwining nanofibres with widths of approximately 80 nm. The ethanol/water ratio has an important influence on the gelation process: the gelator is sparingly soluble in water and soluble in ethanol. The gelator is capable of incorporating anionic drugs in its fibrillar network easily; sodium ibuprofenate, indomethacin and the sodium salt of methotrexate were used as model drugs that were incorporated into the quickly forming gels. The characterization of these composite xerogels was made by different microscopy techniques as well as X-ray powder diffraction. The ability of the amphiphile to form a gel is largely maintained in the presence of the different model drugs and the overall morphology of the gels (that present a fibre like structure in all cases with intertwined ribbons) is very similar. Furthermore the in vitro release of the drugs from the gel and the in vivo anti-inflammatory efficacy was studied. The overall results show better release profiles and anti-inflammatory efficacy for indomethacin, and prove the promise of this molecular gel in controlled drug release, in the present case dermatological application.
Journal of Pharmaceutical Sciences | 2012
E. González-Mira; Saša Nikolić; Ana C. Calpena; M. Antonia Egea; Eliana B. Souto; M. Luisa García
Flurbiprofen (FB)-loaded nanostructured lipid carriers (NLCs) based on Compritol®888 ATO (C888; FB-C888NLC) were developed for anti-inflammatory ocular therapy. NLCs prepared by high-pressure homogenization technique following a factorial design had low particle size (<199 nm), high entrapment efficiency (∼90%), and long-term physical stability. Previously optimized NLCs based on stearic acid (SA; FB-SANLC) were prepared for comparison studies. Both formulations were dispersed in freshly prepared carbomer hydrogel (HG) to check the suitability of semisolid-based NLC HGs to enhance the corneal residence time. FB-C888NLC remained in the nanometric range, whereas FB-SANLC suffered an increase in particle size up to 5 µm after incorporation. Consequently, modifications in the crystalline lattice structure were observed for FB-SANLC-enriched HG (HG_FB-SANLC) by X-ray diffractometry. Both HG formulations showed plastic and low or no thixotropic properties, making them suitable for ocular application while maintaining its predominant elastic component as an indicator of good physicochemical stability. Formulations depicted sustained FB release. Ex vivo permeation analysis in isolated rabbit cornea revealed enhanced transcorneal drug permeation from the systems. In vivo ocular tolerance was confirmed by the Draize test. Therefore, NLC are promising and effective systems for ocular delivery of FB.
European Journal of Pharmaceutics and Biopharmaceutics | 2015
Guadalupe Abrego; Helen L. Alvarado; Eliana B. Souto; Bessy Guevara; Lyda Halbaut Bellowa; Alexander Parra; Ana C. Calpena; María L. García
Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels.
Nanomedicine: Nanotechnology, Biology and Medicine | 2012
Joana Araújo; Maria L. Garcia; Mireia Mallandrich; Eliana B. Souto; Ana C. Calpena
Nanostructured lipid carriers (NLC) have been developed for sustained release of triamcinolone acetonide (TA), a corticosteroid commonly indicated for macular edema, neovascularization, and other ocular inflammatory disorders. TA-NLC were prepared by high-pressure homogenization and characterized for in vitro release by dialysis bag. Ex vivo permeation profile was assessed using rabbit sclera isolated and mounted in Franz diffusion cells. TA-NLC were placed in episcleral donor compartment and choroidal side was perfused with HEPES buffer. Tissue sections underwent drug wash-out, following analysis by validated RP-HPLC of drug content and perfused fractions collected over 24 hours. Drug release followed one-order kinetics and permeability studies confirmed that TA is able to diffuse across rabbit sclera in sustained profile, following zero-order kinetics. Strong tissue binding was observed, providing a drug depot. These findings are of potential use when designing future TA therapy strategies for ocular diseases of posterior segment.