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Offshore hydrocarbon exploration and exploitation are activities developed internationally in the advance of the energy industry. Conflicts generated by incompatibility with others or with social actors, make the approach from Marine Spatial Planning necessary. In Argentina, although it is a process that has been developing since the middle of the 20th century, it was not until 2014 when the National Government promoted the activity. The North Argentine Basin (NAB) constitutes a hydrocarbon exploration area that was delimited in 2018 by Resolution 65/2018. This activity in the NAB has given rise to conflicts between intervening social actors, which was manifested in the Public Hearing (AP1/21) held in July 2021. That is why the objective of this work was to analyze the results of the AP1/21 and contrast them with the opinion of Mar del Plata's residents. For this, 682 semi-open surveys were carried out, where they were asked about the activity and the AP1/21. As a result, it was obtained that 373 people were expressed in favor (4%) and against (96%) of the project. Topics such as climate change, energy planning, and disagreement with the steps of the participatory process and the environmental impact study were presented. In the case of the surveys, opinions similar to those expressed in the audience were found, corroborating results and conclusions between both processes. In summary, the work allowed us to know not only the opinion of Mar del Plata's population but also the type of information available on the economic activity analyzed.The online version contains supplementary material available at 10.1007/s11852-022-00896-x.

Iron oxide nanoparticles are promising nanosystems for designing drug delivery platforms owning to their excellent biocompatibility and unique magnetic properties. Herein, we report for the first time a simple and environmentally friendly methodology for obtaining stable hybrid magnetic nanoplatforms (HMNP) as nanocarriers for tamoxifen (TMX). Thus, Fe3O4 nanoparticles were conjugated with L-cysteine (L-Cys) and/or hyaluronic acid (HA). Two superparamagnetic nanoplatforms, Fe3O4-L-Cys-HA and Fe3O4-HA (11 and 14 nm, respectively), were prepared. Their physicochemical and pharmaceutical properties, biocompatibility and cytotoxic effect against MCF-7 breast cancer cells were evaluated. The incorporation of L-Cys into the Fe3O4-L-Cys-HA HMNP effectively improved their aqueous dispersibility and colloidal stability (up to 8 h). Both HMNP exhibited high TMX loading efficiency (>60%), hydrophilic behavior and magnetic response. TMX was released in a sustained manner and release kinetic data indicated diffusion-controlled release mechanisms. Both HMNP showed high hemocompatibility (% hemolysis ≤5%) and low cytotoxicity against breast normal cells (MCF-10A); the load of TMX into HMNP reduced the hemolyzation of erythrocytes induced by the drug, and led to an unpredicted improved drug efficacy. Four-fold lower concentration of HMNP-TMX (64 μM) improved TMX efficacy against MCF-7 breast cancer cells compared to that of the free drug (256 μM). Thus, the HMNP-TMX increased drug cytotoxicity against tumor cells and reduced drug cytotoxicity in red blood cells, suggesting that they could offer a safety alternative for controlled release of TMX with enhanced efficacy against breast cancer. Furthermore, the modular synthesis reported here opens up an innovative method to rationalize the design and easy preparation of HMNP for nanomedicine.

The idea of employing natural cell membranes as a coating medium for nanoparticles (NPs) endows man-made vectors with natural capabilities and benefits. In addition to retaining the physicochemical characteristics of the NPs, the biomimetic NPs also have the functionality of source cell membranes. It has emerged as a promising approach to enhancing the properties of NPs for drug delivery, immune evasion, imaging, cancer-targeting, and phototherapy sensitivity. Several studies have been reported with a multitude of approaches to reengineering the surface of NPs using biological membranes. Owing to their low immunogenicity and intriguing biomimetic properties, cell-membrane-based biohybrid delivery systems have recently gained a lot of interest as therapeutic delivery systems. This review summarises different kinds of biomimetic NPs reported so far, their fabrication aspects, and their application in the biomedical field. Finally, it briefs on the latest advances available in this biohybrid concept.

The interfacial behaviour of the amphiphilic drug hexadecyl phosphocholine (HePC, also called miltefosine) was analysed by cyclic voltammetry applied at the water/1,2-dichloroethane interface. HePC is the only oral drug currently approved for the treatment of visceral, mucosal and cutaneous leishmaniasis. Because of its amphiphilic character, it can interact with biological membranes, solubilizing their compounds and leading to cell disruption. These interactions are responsible for its side effects and toxicity; therefore, HePC quantification in biological fluids and pharmaceutical preparations is extremely important. However, the lack of a chromophore in its structure prevents its spectroscopic determination. For this reason, the main challenge of this work was to propose an electroanalytical method for the quantification of this drug, which constitutes a simpler alternative than liquid chromatography-tandem mass spectrometry already reported. With this aim, in the first part of this work, the mechanism of the electrochemical process occurring after polarizing the interface was studied. By varying the experimental conditions, it was possible to determine that in a first step, at open circuit or at low potential values, HePC spontaneously adsorbed to the interface. Later, as the potential increased, the transfer of the anions present in the organic phase towards the aqueous side of the interface, where the HePC polar head groups were present, occurred thus forming adsorbed "ion pairs" and producing an increase in positive current. Subsequently, in the negative sweep, the "ion pairs" dissociated and desorbed giving rise to a negative peak. In this way, both negative and positive currents were considered useful for quantitative purposes. In the second part of this work, an appropriate experimental procedure was designed and proposed as a quantitative methodology for the HePC determination, which consisted of cleaning the interface and controlling the time at open circuit, followed by the voltammetric analysis. A linear response of both, positive or negative, peak currents with drug concentration was obtained within an acceptable range, providing a simple solution for the HePC quantification problem. Future studies will be carried out to evaluate the quantification and selectivity in real matrices containing polymer micelles working as HePC nanocarriers with the aim of avoiding the adverse effects of HePC when it is orally or intravenously administered.

This work focusses on the chemical diversification of an Ambrosia tenuifolia extract and its bioguided fractionation, aiming to unveil the chemical entity responsible for the trypanocidal activity. Besides, a revision of the phytochemical study of this species, based on previous reports of the antiparasitic psilostachyins A and C as main compounds, was conducted. To improve the biological properties of a plant extract through a simple chemical reaction, the oxidative diversification of the dichloromethane extract of this plant species was carried out. A bioguided fractionation of a chemically modified extract was performed by evaluating the inhibitory activity against Trypanosoma cruzi trypomastigotes. This experiment led to the isolation of one of the most active compounds. In general terms, epoxidized metabolites were obtained as a result of the oxidation of the major metabolite of the species. The trypanocidal activity of some tested metabolites overperformed the reference drug, benznidazole, displaying no cytotoxicity at trypanocidal concentrations. Key structure-activity relationships were obtained for designing previously undescribed antiparasitic sesquiterpene lactones.

Benznidazole (BZ) is a first-line drug for the treatment of Chagas disease; however, it presents several disadvantages that could hamper its therapeutic success. Multiparticulate drug delivery systems (MDDS) are promising carriers to improve the performance of drugs. We developed BZ-loaded MDDS intended for improving Chagas disease therapy. To assess their efficacy and safety, Trypanosoma (T) cruzi infected BALB/c mice were orally treated with free BZ or BZ-MDDS at different regimens (doses of 50 and 100 mg/kg/day, administered daily or at 2- or 5-days intervals) and compared with infected non-treated (INT) mice. At 100 mg/kg/day, independent of the administration regimen, both treatments were able to override the parasitemia, and at 50 mg/kg/day significantly reduced it compared to INT mice. BZ-MDDS at a dose of 100 mg/kg/day administered every 5 days (BZ-MDDS 100–13d) induced the lowest cardiac parasite load, indicating an improved efficacy with lower total dose of BZ when loaded to the MDDS. Reactive oxygen species produced by leukocytes were higher in INT and mice treated with BZ at 50 mg/kg/day compared to 100 mg/kg/day, likely because of persistent infection. BZ-MDDS treatments markedly reduced heart and liver injury markers compared to INT mice and those receiving the standard treatment. Therefore, BZ-MDDS exhibited enhanced activity against T. cruzi infection even at lower doses and reduced administration frequency compared to free BZ while increasing the treatment safety. They likely avoid undesired side effects of BZ by keeping a sustained concentration, avoiding plasmatic drug peaks. BZ-MDDS evidenced significant improvements in experimental Chagas disease treatment and can be considered as a potential improved therapeutic alternative against this illness.

Cancer is one of the most common life-threatening illness and it is the world’s second largest cause of death. Chemotherapeutic anticancer drugs have many disadvantages, which led to the need to develop novel strategies to overcome these shortcomings. Moreover, tumors are heterogenous in nature and there are various biological barriers that assist in treatment reisistance. In this sense, nanotechnology has provided new strategies for delivery of anticancer therapeutics. Recently, delivery platforms for overcoming biological barriers raised by tumor cells and tumor-bearing hosts have been reported. Among them, amphiphilic block copolymers (ABC)-based self-assembled nanocarriers have attracted researchers worldwide owing to their unique properties. In this work, we addressed different biological barriers for effective cancer treatment along with several strategies to overcome them by using ABC‐based self-assembled nanostructures, with special emphasis in those that have the ability to act as responsive nanocarriers to internal or external environmental clues to trigger release of the payload. These nanocarriers have shown promising properties to revolutionize cancer treatment and diagnosis, but there are still challenges for their successful translation to clinical applications. Fil: Torres, Jazmin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Dhas, Namdev. Nirma University. Institute Of Pharmacy; India Fil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Advanced micro- and nanomaterial therapeutic systems exhibit several advantages over conventional therapeutic systems. Great progresses in the development of improved drug delivery systems (DDS), including lipid-based and polymer-based carriers, have been observed in the past decades. DDSs attempt to improve the therapeutic effect of drugs mainly by controlling their release, which allows modifying the pharmacokinetics of drugs and diminishing their toxic and side effects. Targeted delivery of drugs to specific sites of action comprises a big challenge in the field of pharmaceutical sciences. In this scenario, this chapter aims to cover the main aspects regarding lipid-based and polymer-based carriers. Information related to their development and applications as therapeutic carriers for controlled drug release will be highlighted.

Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug’ performance. Benznidazole (BZ) is the first–line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration. Physicochemical characterizations were studied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDS composed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wet granulation methods with yields >83%. FT-IR demonstrated ionic interaction between the polyelectrolytes. Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles. The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatin-capsules. The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results. MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q15min > 85%), while an extended release (Q120min ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of two MDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapy in the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduce parasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment. Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatment of Chagas disease. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Martinelli, Marisa. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina; Argentina Fil: Ponce, Nicolás Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Sanmarco, Liliana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Layered double hydroxides (LDHs) have been proposed as delivery systems (DSs) of (fluoro)quinolones (QLNs) to overcome their low bioavailability and to prevent the emergence of resistant bacteria. Both LDH-DS synthesis as nanoparticles (NPs) and QLN interactions with the metal ions that constitute the layers are essential to improve their physicochemical, biopharmaceutical and antimicrobial properties. Here, LDH-DSs containing the basic form of nalidixic acid (Nal), used as a probe, were obtained by coprecipitation at variable and constant pH (LDH-Nal-pHvar and LDH-Nal-pHcte, respectively). For both syntheses, LDH NPs containing Nal anions (LDH-Nal-NPs), with sizes between 30 and 40 nm, were obtained. A coordination compound (Mg(Nal)2·4H2O, Mg(Nal)2) was also concurrent for LDH-Nal-pHcte, which modulated the drug release profile and antimicrobial properties of the LDH-Nal-NPs. Thus, Nal release from LDH-Nal-pHvar was produced mainly by anion exchange. The best fits, obtained for the Higuchi model, showed rate constants dependent on the exchanging anions (kH = 0.88 and 1.53 for NaCl 0.9% and buffer phosphate 0.05 M, pH = 7.4, respectively). The nanometric size of LDH-Nal-pHvar as well as its faster release rate allowed a minimum inhibitory concentration decrease (MIC = 32 μg mL−1) compared to the pure drug (MIC = 128 μg mL−1). Instead, the presence of Mg(Nal)2 in LDH-Nal-pHcte led to a more sustained and media independent Nal release, but a lower MIC (64 μg mL−1) than LDH-Nal-pHvar. Fil: Salguero Salas, Yadira Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Mosconi, Giuliana. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina Fil: Rojas Delgado, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina

The bioadhesive polymeric films as topical drug delivery systems are interesting alternatives to improve the pharmacotherapy and patient compliances. New derivate biomaterials based on weisocyanate- dendronized PVP- crosslinked chitosan and loaded with ciprofloxacin (CIP), as model drug, were used to prepare bioadhesive films. Relevant in vitro/in vivo attributes to define main physicochemical and biopharmaceutical characteristics for topical wound-healing applications were evaluated. A high proportion of CIP, uniformly dispersed along throughout the film, was loaded. An extended release of CIP and different behaviors of release profiles, depending on the presence of dendron, were observed. The films loaded with CIP were effective in inhibiting the growth of both Gram positive and Gram negative bacteria. In addition, biocompatibility and bioadhesion into conjuntival-sacs of the rabbits suggests that these films have good properties to be applied over skin wounds for topical applications, allowing a reduction of the frequency of administration and improving the residence time of the films. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Aldana, Ana Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Tartara, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Alovero, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo En Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo En Ingeniería de Procesos y Química Aplicada.; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Martinelli, Marisa. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo En Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo En Ingeniería de Procesos y Química Aplicada.; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Black Phosphorous has recently gained the attention in the field of 2D nanomaterials owing to its exceptional structure and properties. Specifically, its features like drug loading efficiency, biocompatibility, optical, mechanical, electrical, thermal and phototherapeutic properties contribute to its rising demand as potential alternative to the graphene-based 2D nanomaterials in biomedical applications. Though the BP’s outlook appears promising, its practical applicability is highly challenging. In this review we have discussed the different strategies for synthesis of BP and then briefed its unique properties which renders it a potential platform for the biomedical application. We then discuss the importance of heterogeneous doping on improving the stability of BP against chemical degradation and enhancing its photoelectric properties. Meanwhile, BP-based nanoconjugates, stimuli responsive nanoplatforms, therapeutic, imaging and biosensing platforms are the domains of special and comprehensive interest for versatile biomedical applications of BP. The physicochemical interactions at the nano-bio interface like protein corona formation on the surface on nanoparticles due to interaction with the plasma proteins and others play a crucial role in the biological effects of BP. Hence, we have also discussed the recent studies on interactions between Black phosphorus based nanoconstructs with various biological molecules. Further, it is vital to consider the fact that, though biocompatible, BP-nanomaterials can induce inflammatory responses and exhibit toxicity in dose and time dependant manner. Therefore, we have briefed the biodegradation and toxicological aspects of BP to enlighten the readers about the safety and toxicity of black phosphorous. The future developments of this 2D nanomaterial will not only serve as a boon for oncology, but also functions as a potential nanoplatform for other biomedical applications.

Nanomaterials for biomedical applications continuously lead researchers to design novel tools and strategies. Hybrid nanomaterials have recently been examined as promising platforms for therapeutic applications. This unique class of nanomaterials retains advantageous features of both the inorganic and the organic components and provides the ability to tune the properties of the nanohybrid through the combination of functional components. This chapter summarizes advances in the design and biomedical applications of hybrid nanomaterials that fall into two main categories: organic–organic and organic–inorganic hybrids, including lipid–polymer-, clay-, carbon-, and metal–metal oxide-based nanohybrids. Their applications as nanotherapeutics for controlled drug release are highlighted.

There is a considerable research interest in polymers for drug delivery systems in the medical and pharmaceutical field. Several polymeric materials have been investigated in the development of nanostructures for drug delivery to increase therapeutic advantages while minimizing side effects. The cutting-edge and emerging research focuses involve the design and development of stimuli-responsive materials. In particular, polymersomes are artificial polymeric vesicles that have received significant attention due to their entangled architecture. Smart polymersomes can recognize some environmental stimuli and release the drug loaded in dose-, spatial-, and temporal-controlled manners. This chapter aims to cover the recent advances in biological-stimuli-responsive and external-stimuli-responsive polymersomes. Aspects related to the mechanism involved in the drug release and some examples of their main biomedical applications will be highlighted. Also, the use of stimuli-responsive polymersomes for cancer therapy will be stressed.

Response to stimulus is a basic process of living organisms. Over the past 30 years many interesting biomedical uses have been proposed for stimuli-responsive polymers, including uses in diagnostics, drug delivery, tissue engineering and regenerative medicine, bioseparations, sensors, and cell culture. Many polymers have been investigated in order to develop carrier systems for drug delivery to increase therapeutic advantages while minimizing side effects. Internal and/or external microenvironment such as pH, ionic strength, magnetic field, temperature, enzyme, glucose, redox potential, light, or a combination of them, can stimuli the response of polymers and is useful for the controlled release of bioactive compounds. These responses are manifested as dramatic changes in one of the following: shape, surface characteristics, solubility, formation of an intricate molecular self-assembly, or a sol-to-gel transition. This chapter briefly overviews the field of ionic-strength-responsive polymers and describes some of the most successful biomedical applications of such smart polymers.

Films based on biopolymers and loaded with antimicrobial agents are convenient pharmaceutical dosage forms for topical application. Inorganic carriers loaded with these agents lead to composite materials, which combined with polymers produce further functionality. Here, hybrid composite films based on layered double hydroxide (LDH) and hyaluronan (HS) as ciprofloxacin (Cip) delivery systems were studied as an alternative for prophylaxis and treatment of opportunistic infections in wounds. Cip-intercalated Zn-Al LDH (LDH-Cip), with high drug loading and crystallinity, were obtained by a precipitation at variable pH method, and then included in a HS dispersion for obtaining the hybrid composite films by solvent casting. Physicochemical characterization of films showed that a composite material where the HS acted as matrix and LDH-Cip aggregates acted as filler were obtained. LDH-Cip were uniformly dispersed along the (LDH-Cip)/HS films, which exhibited roughness in their surface, increasing their swelling capacity in PBS pH = 5.8. Controlled releases of Cip toward PBS at pH = 5.8 and 7.4 were obtained, and the best fits for the release profiles were found with Higuchi and Korsmeyer-Peppas models, respectively. (LDH-Cip)/HS films exhibited antimicrobial activity against S. aureus. These films would then provide sustained release of Cip after topical administration, maintaining a suitable level of antibacterial activity, combined with the wound healing properties of the HS. The interesting properties shown by the (LDH-Cip)/HS films make them a promising alternative for application in skin wounds.

Damaged cells release the pro-inflammatory signal ATP, which is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine (ADO). The balance between ATP/ADO is known to determine the outcome of inflammation/infection. However, modulation of the local immune response in different tissues due to changes in the balance of purinergic metabolites has yet to be investigated. Here, we explored the contribution of CD73-derived ADO on the acute immune response against Trypanosoma cruzi parasite, which invades and proliferates within different target tissues. Deficiency of CD73 activity led to an enhanced cardiac microbicidal immune response with an augmented frequency of macrophages with inflammatory phenotype and increased CD8+ T cell effector functions. The increment of local inducible nitric oxide (NO) synthase (iNOS)+ macrophages and the consequent rise of myocardial NO production in association with reduced ADO levels induced protection against T. cruzi infection as observed by the diminished cardiac parasite burden compared to their wild-type (WT) counterpart. Unexpectedly, parasitemia was substantially raised in CD73KO mice in comparison with WT mice, suggesting the existence of tissue reservoir/s outside myocardium. Indeed, CD73KO liver and visceral adipose tissue (VAT) showed increased parasite burden associated with a reduced ATP/ADO ratio and the lack of substantial microbicidal immune response. These data reveal that the purinergic system has a tissue-dependent impact on the host immune response against T. cruzi infection.

Benznidazole (BZ), first-line drug for Chagas treatment, is available as immediate-release tablets. High frequency of administration, long-term therapy, and side effects of BZ conspire against treatment adherence, and negatively impact in therapeutic success. We have developed BZ-loaded interpolyelectrolyte complexes (IPECs) composed of polymethacrylates (EE-EL-BZ) or polysaccharides (Ch-AA-BZ) for controlled BZ release. This work aimed to evaluate their preclinical pharmacokinetics compared to Abarax® (reference treatment) and to correlate them with the in vitro BZ release. A randomization schedule with a 3 × 2 cross-over design was used. Each healthy dog received a single oral dose of 100 mg of BZ from EE-EL-BZ, Ch-AA-BZ or Abarax®. BZ quantification was performed in plasma by a validated HPLC-UV method. Moreover, in silico simulations using the pharmacokinetic software PK Solutions 2.0™ were calculated for the multiple-dose administration at two dose regimens: 100 mg of BZ administered every 12 and 24 h. Also, the relationship between in vitro dissolution and in vivo plasma BZ concentration profiles in a single step was model for IVIVC analysis. BZ was rapidly absorbed from all formulations. The Cmax value for Ch-AA-BZ was 32% higher than reference (p < 0.05) and an earlier Tmax (4.2 h) was observed as compared to EE-EL-BZ (6.0 h). For both IPECs, the Tmax values were higher (p < 0.05) and the areas under the curve were 25% greater than those of Abarax® (p < 0.01). Despite these variations in pharmacokinetics parameters, simulations of once or twice daily dosing showed that all formulations reached a steady-state range concentration above of the minimum therapeutic dose while avoiding high BZ concentrations related to increased side effects. A linear level A IVIVC model was established using plasma concentration profiles and dissolved data obtained. Thus, BZ-loaded IPECs prolonged drug release and formulated as capsules showed improved in vivo performance, in terms of bioavailability and Tmax values, which were significantly higher compared to Abarax®. These BZ carrier systems would be useful for oral administration in the treatment of Chagas disease. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Guzman, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Himelfarb, Martin Alejandro. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Litterio, Nicolas Javier. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Olivera, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Polysaccharides-based delivery systems and interpolyelectrolyte complexes (IPECs) are interesting alternatives to control the release of drugs, thereby improving therapies. Benznidazole (BZ) is the selected drug for Chagas disease pharmacotherapy. However, its side effects limit its efficacy and safety. We developed novel multiparticulated BZ-loaded IPECs based on chitosan and alginic acid, and investigated their physicochemical and pharmacotechnical properties. IPECs were obtained using the casting solvent method, followed by wet granulation. They presented ionic interaction between the biopolymers, revealed that free BZ was uniformly distributed and showed adequate flow properties for hard gelatin-capsule formulation. The multiparticles exhibited mucoadhesion properties and revealed modulation of BZ release, depending on the release media, in accordance with the fluid uptake. The IPECs developed possess interesting properties that are promising for the design of novel alternatives to improve Chagas disease pharmacotherapy, which would diminish BZ's adverse effects and/or allow a reduction in the frequency of BZ administration. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Therapeutically effective and biocompatible nanomaterials based on polymer and lipid carriers continuously lead researchers to design novel tools and strategies. Because of their potential ability to improve current therapies, these nanodevices are extensively used as delivery devices for drugs and/or imaging agents to improve the efficacy and safety of treatments by increasing therapeutic performance and reducing side effects of several drugs, proteins, and vaccines. Among all the approaches proposed in recent years, this chapter presents the most outstanding contributions of self-assembled nanomaterials, because they have been identified as one of the key subjects in nanoscience. We will focus on preparation and characterization methods and on the main biomedical applications reported in recent years.

Biopolymers have attracted considerable interest for the development of drug delivery systems (DDSs) owing to their biocompatibility, nontoxicity, renewability, and mild processing conditions. These polymers are degradable in vivo, either enzymatically or nonenzymatically, and can be metabolized and excreted via normal physiological pathways. Application of biopolymers in living systems would reduce immunological reactions and toxicity that occur when a synthetic polymer is used in a host. There are currently many different biopolymers reported in the literature that have been evaluated for use in the development of DDSs. In this context, this chapter presents the outstanding contributions in the area of biopolymeric nanoparticles as DDSs, including the main types of biopolymers used in their preparation.

Nanogels have attracted growing interest in the last five decades owing to their potential for biomedical applications, including drug delivery systems and bioimaging. They are able to encapsulate highly amounts of biologically active agents such as drugs, proteins, and genetic material inside the polymer networks and release them in a controlled manner. Internal and external microenvironmental such as pH, ionic force, magnetic field, temperature, enzyme, glucose, redox potential, light, or a combination of them, can stimuli the response of nanogels and are useful for the controlled release of bioactive compounds. This chapter aims to cover the main features regarding the most outstanding contributions in the area of drug delivery from stimulus responsive nanogels. The recent advances in their main biomedical applications and physicochemical attributes for potential application of nanogels in cancer treatment will be highlighted. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Cuggino, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Objective: To develop an extemporaneous 1% benznidazole (BNZ) suspension, with masked taste and adequate stability starting from available commercial tablets. The quality of compounding was evaluated through content uniformity measurement and physical and microbiological stability evaluation, under different storage conditions during 90 days. Methods: Six batches of 1% BNZ suspension were prepared using safe excipients currently available in a galenic area of Hospital Pharmacy and then stored at 5 and 25 °C for 90 days. The BNZ content was determined by UV spectrophotometry. Physical stability was defined as the absence of colour, odour and/or flavour changes and the re-suspension of solid phase by a reasonable amount of simple 15-s shaking. The compliance with microbiological attributes of non-sterile pharmaceutical products was also evaluated. Results: An oral liquid suspension, containing 1% of BNZ, was developed from commercially available BNZ tablets. The formulations stored for 90 days were easily re-dispersed after a simple 15-s shaking, ensuring the pouring of a liquid volume containing the desired dose of BNZ. All samples were within the acceptable range of BNZ concentration with minimal standard deviations. There were no detectable changes in colour, odour, viscosity, pH and microbial growth, complying with official quality requirements. The quality attributes were not affected by storage, room or refrigeration conditions or by the frequent opening or closing of the multidose containers. Conclusion: Paediatric oral liquid suspension containing 1.0% of BNZ was easily prepared starting from commercial tablets, being an interesting alternative for optimising the paediatric treatment of Chagas disease. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Miltefosine presents antineoplastic activity but high hemolytic potential. Its use in cancer has been limited to treating cutaneous metastasis of breast cancer. To decrease hemolytic potential, we developed a formulation of miltefosine-loaded polymeric micelles (PM) of the copolymer Pluronic-F127. A central composite design was applied and the analysis of variance showed that the optimum level of hydrodynamic diameter and polydispersity index predicted by the model and experimentally confirmed were 29 nm and 0.105, respectively. Thermal analyses confirmed that miltefosine was molecularly dispersed within PM. Pluronic-F127 PM with miltefosine 80 μM presented a significant reduction of hemolytic effect (80%, p < 0.05) in comparison to free drug. In vitro assays against HeLa carcinoma cells demonstrated similar cytotoxicity to free miltefosine and PM. Our results suggest that, by lowering hemolytic potential, miltefosine-loaded Pluronic-F127 PM a promising alternative to broaden this drug use in cancer therapy, as well as of other alkylphosphocholines. Fil: Valenzuela Oses, Johanna K.. Universidade de Sao Paulo; Brasil Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Feitosa, Valker A.. Universidade de Sao Paulo; Brasil. Institute for Technological Research; Brasil Fil: Pachioni Vasconcelos, Juliana A.. Universidade de Sao Paulo; Brasil Fil: Gomes-Filho, Sandro M.. Universidade de Sao Paulo; Brasil Fil: Lourenço, Felipe R.. Universidade de Sao Paulo; Brasil Fil: Cerize, Natalia N.P.. Institute for Technological Research; Brasil Fil: Bassères, Daniela S.. Universidade de Sao Paulo; Brasil Fil: Rangel-Yagui, Carlota O.. Universidade de Sao Paulo; Brasil

The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both ofwhich are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skinwere achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, thefinal product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications. Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Cuggino, Julio César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina Fil: Rosset, Clarisa Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Paez, Paulina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Alovero, Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Alvarez Igarzabal, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Increasing evidence demonstrates that generation of extracellular adenosine from ATP, which is hydrolyzed by the CD39/CD73 enzyme pair, attenuates the inflammatory response and deactivates macrophage antimicrobial mechanisms. Although CD73 is emerging as a critical pathway and therapeutic target in cardiovascular disorders, the involvement of this ectonucleotidase during myocardial infection has not been explored. Using a murine model of infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy, we observed a sudden switch from the classical M1 macrophage (microbicidal) phenotype toward an alternative M2 (repairing/anti-inflammatory) phenotype that occurred within the myocardium very shortly after BALB/c mice infection. The observed shift in M1/M2 rate correlated with the cardiac cytokine milieu. Considering that parasite persistence within myocardium is a necessary and sufficient condition for the development of the chronic myocarditis, we hypothesized that CD73 activity may counteract cardiac macrophage microbicidal polarization, rendering the local immune response less effective. In fact, a transient treatment with a specific CD73 inhibitor (adenosine 5′-α,β-methylene-diphosphate) enhanced the microbicidal M1 subset predominance, diminished IL-4– and IL-10–producing CD4+ T cells, promoted a proinflammatory cytokine milieu, and reduced parasite load within the myocardium during the acute phase. As a direct consequence of these events, there was a reduction in serum levels of creatine kinase muscle–brain isoenzyme, a myocardial-specific injury marker, and an improvement in the electrocardiographic characteristics during the chronic phase. Our results demonstrate that this purinergic system drives the myocardial immune response postinfection and harbors a promising potential as a therapeutic target.

The current study is focused on physicochemical characterization and in vitro drug delivery evaluation ofself-organized nanoparticles based on drug-interpolyelectrolyte complexes (DIPEC). The interactionbetween two oppositely charged polymethacrylates, Eudragit® EPO and L100, and four non-steroidalanti-inflammatory drugs, Salicylic Acid, Benzoic Acid, Ketoprofen and Naproxen was studied.DIPEC nanoparticles produce translucent and stable aqueous dispersions where a remarkably highproportion of drug (between 57 and 95%) is condensed with polyelectrolyte (PE) under the form of ionicpairs. They exhibited particle size in the range of 120e198 nm and high positive zeta potential,contributing to physical stability. The sign of zeta potential shifted from positive to negative by changesin composition of DIPEC. Thermal analysis and X-ray diffraction patterns of freeze dried DIPEC showedthe amorphous state of products and the complete interaction of PE and drug. Solid complexes wereeasily redispersed in water yielding nearly the same parameters of fresh dispersions. In vitro releaseexperiments showed that DIPEC nanodispersions behave as drug reservoirs, exhibiting a slow drugrelease rate in water, which significantly increased in simulating physiological fluids, promoted by ionicexchange. They also exhibited a remarkable robustness towards simulated physiological media ofdifferent pH. Fil: Palena, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina

Pollen traps were used to sample pollen loads collected by Apis mellifera through the day, their botanical origins were determined and variations in their weights were studied. Differences were observed in the mean load weights collected in the different periods of the day. The heaviest loads were recorded at midday or at the beginning of the afternoon. Considerable differences were found between the mean load weights from the different species, those of Fedia cornucopiae and Fragaria vesca being the heaviest ones. The different intensity with which the bees collected each pollen resource does not explain the differences in weight between the loads for the different species. The results also show that the pollen grain size and the presence or absence of nectar are not determining factors of the mean load weight for each species. Each species showed a different pattern of variation in load weights through the day. The predominating cases were those in which the heaviest loads were collected at midday or at...

We left pollen traps in two hives at Hinojos (Huelva, Spain) for two days. We removed the pollen loads accumulating on the trays of the trap four times each day and studied their botanical origin. In the two days of sampling, the number of pollen resources and their relative intensity of exploitation varied through the day. Pollen collection was more diverse in the central parts of the day, whereas the use of resources tended to be progressively more uniform through the day.