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1.
Sci Rep ; 14(1): 13737, 2024 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877119

RESUMO

Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments. Furthermore, dedifferentiation can occur providing relapse of the disease. In this study we evaluated fenretinide, a semisynthetic ATRA derivative, encapsulated in nanomicelles (nano-fenretinide) as an alternative treatment to ATRA in APL. Nano-fenretinide was prepared by fenretinide encapsulation in a self-assembling phospholipid mixture. Physico-chemical characterization was carried out by dinamic light scattering and spectrophotometry. The biological activity was evaluated by MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Nano-fenretinide induced apoptosis in acute promyelocytic leukemia cells (HL60) by an early increase of reactive oxygen species and a mitochondrial potential decrease. The fenretinide concentration that induced 90-100% decrease in cell viability was about 2.0 µM at 24 h, a concentration easily achievable in vivo when nano-fenretinide is administered by oral or intravenous route, as demonstrated in previous studies. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA.


Assuntos
Apoptose , Fenretinida , Leucemia Promielocítica Aguda , Humanos , Fenretinida/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Leucemia Promielocítica Aguda/metabolismo , Células HL-60 , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , Sobrevivência Celular/efeitos dos fármacos , Micelas , Potencial da Membrana Mitocondrial/efeitos dos fármacos
2.
Materials (Basel) ; 17(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38591542

RESUMO

Recent studies have shown that the mechanical properties of bioinspired periodic composite materials can be strongly influenced by finite deformation effects, leading to highly nonlinear static and dynamic behaviors at multiple length scales. For instance, in porous periodic nacre-like microstructures, microscopic and macroscopic instabilities may occur for a given uniaxial loading process and, as a consequence, wave attenuation properties may evolve as a function of the microstructural evolution, designating it as metamaterials. The numerical outcomes provide new opportunities to design bioinspired, soft composite metamaterials characterized by high deformability and enhanced elastic wave attenuation capabilities given by the insertion of voids and lead cores.

3.
J Colloid Interface Sci ; 662: 446-459, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364470

RESUMO

Lipid nanoparticles own a remarkable potential in nanomedicine, only partially disclosed. While the clinical use of liposomes and cationic lipid-nucleic acid complexes is well-established, liquid lipid nanoparticles (nanoemulsions), solid lipid nanoparticles, and nanostructured lipid carriers have even greater possibilities. However, they face obstacles in being used in clinics due to a lack of understanding about the molecular mechanisms controlling their drug loading and release, interactions with the biological environment (such as the protein corona), and shelf-life stability. To create effective drug delivery carriers and successfully translate bench research to clinical settings, it is crucial to have a thorough understanding of the internal structure of lipid nanoparticles. Through synchrotron small-angle X-ray scattering experiments, we determined the spatial distribution and internal structure of the nanoparticles' lipid, surfactant, and the bound water in them. The nanoparticles themselves have a barrel-like shape that consists of coplanar lipid platelets (specifically cetyl palmitate) that are covered by loosely spaced polysorbate 80 surfactant molecules, whose polar heads retain a large amount of bound water. To reduce the interface cost of bound water with unbound water without stacking, the platelets collapse onto each other. This internal structure challenges the classical core-shell model typically used to describe solid lipid nanoparticles and could play a significant role in drug loading and release, biological fluid interaction, and nanoparticle stability, making our findings valuable for the rational design of lipid-based nanoparticles.


Assuntos
Lipossomos , Nanopartículas , Raios X , Nanopartículas/química , Portadores de Fármacos/química , Tensoativos/química , Lipídeos/química , Água/química , Tamanho da Partícula
4.
Antioxidants (Basel) ; 12(2)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36830027

RESUMO

Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood flow improvement or blood pressure and glycemia reduction, as well as cognitive function improvement. Unfortunately, polyphenol content is reduced during cocoa fermentation, drying, roasting and all the other phases involved in the chocolate production. Here, we investigated the evolution of the polyphenol content during all the different steps of chocolate production, with a special emphasis on roasting (3 different roasting cycles with 80, 100, and 130 °C as maximum temperature). Samples were followed throughout all processes by evaluating the total polyphenols content, the antioxidant power, the epicatechin content, and epicatechin mean degree of polymerization (phloroglucinol adducts method). Results showed a similar trend for total polyphenol content and antioxidant power with an unexpected bell-shaped curve: an increase followed by a decrease for the three different roasting temperatures. At the intermediate temperature (100 °C), the higher polyphenol content was found just after roasting. The epicatechin content had a trend similar to that of total polyphenol content but, interestingly, the mean degree of polymerization data had the opposite behavior with some deviation in the case of the highest temperature, probably due to epicatechin degradation. It seems likely that roasting can free epicatechin from oligomers, as a consequence of oligomers remodeling.

5.
Pharmaceutics ; 15(2)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36839972

RESUMO

Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2 antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential. Strategies to increase the efficacy of anti-GD2 antibodies are actively sought, with the aim to enable chronic treatments that could eradicate minimal residual disease and subsequent relapses, often occurring after treatment. Here, we report that Nanofenretinide and Nanospermidine improved the expression of GD2 in neuroblastoma cells (CHP-134) and provided different effects in combination with the anti-GD2 antibody naxitamab. In particular, Nanofenretinide significantly increased the cytotoxic effect of naxitamab while Nanospermidine inhibited cell motility at extents proportional to naxitamab concentration. In neuroblastoma cells characterized by a low and heterogeneous basal expression of GD2, such as SH-SY5Y, which may represent the cell heterogeneity in tumors after chemotherapy, both Nanofenretinide and Nanospermidine increased GD2 expression in approximately 50% of cells, thus shifting the tumor population towards improved sensitivity to anti-GD2 antibodies.

6.
Front Med Technol ; 4: 909943, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782575

RESUMO

Multicellular tumor spheroids are largely exploited in cancer research since they are more predictive than bi-dimensional cell cultures. Nanomedicine would benefit from the integration of this three-dimensional in vitro model in screening protocols. In this brief work, we discuss some of the issues that cancer nanomedicine will need to consider in the switch from bi-dimensional to three-dimensional multicellular tumor spheroid models.

7.
Molecules ; 27(12)2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35744886

RESUMO

Osteosarcoma (OS) is a malignant disease characterized by poor prognosis due to a high incidence of metastasis and chemoresistance. Recently, Licochalcone A (Lic-A) has been reported as a promising agent against OS. Starting from chalcones selected from a wide in-house library, a new series was designed and synthetized. The antitumor activity of the compounds was tested on the MG63 OS cell line through the innovative Quantitative Phase Imaging technique and MTT assay. To further investigate the biological profile of active derivatives, cell cycle progression and apoptosis induction were evaluated. An earlier and more consistent arrest in the G2-M phase with respect to Lic-A was observed. Moreover, apoptosis was assessed by Annexin V staining as well as by the detection of typical morphological features of apoptotic cells. Among the selected compounds, 1e, 1q, and 1r proved to be the most promising antitumor molecules. This study pointed out that an integrated methodological approach may constitute a valuable platform for the rapid screening of large series of compounds.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Chalcona , Chalconas , Osteossarcoma , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Chalcona/farmacologia , Chalconas/farmacologia , Chalconas/uso terapêutico , Humanos , Osteossarcoma/patologia
8.
Pharmaceutics ; 14(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35745787

RESUMO

A new strategy to cause cell death in tumors might be the increase of intracellular polyamines at concentrations above their physiological values to trigger the production of oxidation metabolites at levels exceeding cell tolerance. To test this hypothesis, we prepared nanospermidine as a carrier for spermidine penetration into the cells, able to escape the polyamine transport system that strictly regulates intracellular polyamine levels. Nanospermidine was prepared by spermidine encapsulation in nanomicelles and was characterized by size, zeta potential, loading, dimensional stability to dilution, and stability to spermidine leakage. Antitumor activity, ROS production, and cell penetration ability were evaluated in vitro in two neuroblastoma cell lines (NLF and BR6). Nanospermidine was tested as a single agent and in combination with nanofenretinide. Free spermidine was also tested as a comparison. The results indicated that the nanomicelles successfully transported spermidine into the cells inducing cell death in a concentration range (150-200 µM) tenfold lower than that required to provide similar cytotoxicity with free spermidine (1500-2000 µM). Nanofenretinide provided a cytostatic effect in combination with the lowest nanospermidine concentrations evaluated and slightly improved nanospermidine cytotoxicity at the highest concentrations. These data suggest that nanospermidine has the potential to become a new approach in cancer treatment. At the cellular level, in fact, it exploits polyamine catabolism by means of biocompatible doses of spermidine and, in vivo settings, it can exploit the selective accumulation of nanomedicines at the tumor site. Nanofenretinide combination further improves its efficacy. Furthermore, the proven ability of spermidine to activate macrophages and lymphocytes suggests that nanospermidine could inhibit immunosuppression in the tumor environment.

9.
Int J Mol Sci ; 24(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36614168

RESUMO

Different molecular mechanisms contribute to the development of multidrug resistance in cancer, including increased drug efflux, enhanced cellular repair mechanisms and alterations of drug metabolism or drug targets. ABCG2 is a member of the ATP-binding cassette superfamily transporters that promotes drug efflux, inducing chemotherapeutic resistance in malignant cells. In this context, the development of selective ABCG2 inhibitors might be a suitable strategy to improve chemotherapy efficacy. Thus, through a multidisciplinary approach, we identified a new ABCG2 selective inhibitor (8), highlighting its ability to increase mitoxantrone cytotoxicity in both hepatocellular carcinoma (EC50from 8.67 ± 2.65 to 1.25 ± 0.80 µM) and transfected breast cancer cell lines (EC50from 9.92 ± 2.32 to 2.45 ± 1.40 µM). Moreover, mitoxantrone co-administration in both transfected and non-transfected HEK293 revealed that compound 8 notably lowered the mitoxantrone EC50, demonstrating its efficacy along with the importance of the ABCG2 extrusion pump overexpression in MDR reversion. These results were corroborated by evaluating the effect of inhibitor 8 on mitoxantrone cell uptake in multicellular tumor spheroids and via proteomic experiments.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Células HEK293 , Mitoxantrona/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteômica
10.
Pharmaceutics ; 13(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34575599

RESUMO

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization.

11.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502132

RESUMO

Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived peptides, named LRAP, TRAP, SP, and C11, in bone tissue engineering. Interestingly, these peptides seem to maintain or even improve the biological activity of the full-length protein, which has received attention in the field of bone regeneration. In this article, the authors combined a systematic and a narrative review. The former is focused on the existing scientific evidence on LRAP, TRAP, SP, and C11's ability to induce the production of mineralized extracellular matrix, while the latter is concentrated on the structure and function of amelogenin and amelogenin-derived peptides. Overall, the collected data suggest that LRAP and SP are able to induce stromal stem cell differentiation towards osteoblastic phenotypes; specifically, SP seems to be more reliable in bone regenerative approaches due to its osteoinduction and the absence of immunogenicity. However, even if some evidence is convincing, the limited number of studies and the scarcity of in vivo studies force us to wait for further investigations before drawing a solid final statement on the real potential of amelogenin-derived peptides in bone tissue engineering.


Assuntos
Amelogenina/metabolismo , Regeneração Óssea/fisiologia , Peptídeos/metabolismo , Amelogenina/química , Amelogenina/genética , Sequência de Aminoácidos , Animais , Biomarcadores , Diferenciação Celular , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos/química , Engenharia Tecidual , Pesquisa Translacional Biomédica
12.
Langmuir ; 36(21): 5745-5753, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32370512

RESUMO

Critical micelle concentration (CMC) is the main chemical-physical parameter to be determined for pure surfactants for their characterization in terms of surface activity and self-assembled aggregation. The CMC values can be calculated from different techniques (e.g., tensiometry, conductivity, fluorescence spectroscopy), able to follow the variation of a physical property with surfactant concentrations. Different mathematical approaches have been applied for the determination of CMC values from the raw experimental data. Most of them are independent of the operator, despite not all of the fitting procedures employed so far can be applied in all techniques. In this experimental work, the second derivative of the experimental data has been proposed as a unique approach to determine the CMC values from different techniques (tensiometry, conductimetry, densimetry, spectrofluorimetry, and high-resolution ultrasound spectroscopy). To this end, the CMC values of five different surfactants, specifically three anionic (sodium dodecyl sulfate, sodium deoxycolate, and N-lauroyl sarcosinate) and two nonionic, such as polyethylene glycol ester surfactants [polyethylenglicol (8) monostearate and polyethylenglicol (8) monolaurate], have been determined by this approach. The "second-derivate" approach provides a reliable determination of the CMC values among all of the techniques investigated, which were comparable to those calculated by the other operator-free routinely methods employed, such as segmental linear regression or Boltzmann regression. This study also highlighted the strengths and shortcomings of each technique over the others, providing an overview of the CMC values of commonly used anionic and nonionic surfactants in the pharmaceutical field, determined by employing different experimental approaches.

13.
Pharmacy (Basel) ; 8(1)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143432

RESUMO

COPHELA (Cooperation in Quality Assurance for Pharmacy Education and Training between Europe and Latin America), a collaborative project between the European Union (EU) and Latin America, will produce on-line courses for the master degree in pharmacy. The program runs from 2019 through 2021. It is funded by the Erasmus+ program of the Education, Audio-visual and Culture Executive Agency (EACEA) of the European Commission. The partners are EU and Latin American universities. These are accompanied by associated partners from EU and Latin American universities, as well as from governmental and non-governmental organizations, such as pharmacy chambers and educational associations. The project is coordinated by the University of Granada, Spain (first author of this paper). It will produce distance learning master degree courses in a dozen fields of specialized pharmaceutical science education and practice, ranging from patient care to industrial pharmacy. This paper describes the design of the project and is intended to evoke constructive comments. It also represents a call for the recruitment of additional associated partners.

14.
Int J Pharm ; 580: 119235, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32194212

RESUMO

The performances of poly(lactic-co-glycolic acid) drug delivery systems are affected by the molecular interactions established between the drug and the polymer matrix as well as by the physical state of the drug embedded. Indeed, the drug may induce polymer plasticization with a drastic change in the release kinetics and medicinal product performances. The aim of this study was to better understand the interactions between poly(lactic-co-glycolic acid) and ketoprofen, the latter known to plasticize hydrophilic and hydrophobic polymers. Ketoprofen interacts with poly(lactic-co-glycolic acid) exerting a maximum plasticizing effect at weight fractions around 0.25. Higher ketoprofen amounts form heterogeneous mixtures with the non-soluble molecules dispersed in the matrix as crystals or amorphous domains, depending on the preparation method. Unexpectedly, the amorphous ketoprofen dispersed in the poly(lactic-co-glycolic acid) matrix is remarkably stable. H-bonding seems responsible for the glass transition temperature reduction and the limited solubility. Brillouin spectroscopy and molecular dynamics simulation data suggest that ketoprofen solubility increases with temperature and non-polar interactions are responsible for this phenomenon.


Assuntos
Cetoprofeno/química , Poliglactina 910/química , Materiais Biocompatíveis/química , Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Cinética , Simulação de Dinâmica Molecular , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Solubilidade/efeitos dos fármacos , Análise Espectral/métodos , Temperatura
15.
Mol Pharm ; 16(6): 2430-2444, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-30969129

RESUMO

Cancer remains one of the most important challenges in biomedical sciences. Chemotherapeutic agents are very potent molecules that exhibit a significant level of toxicity in numerous tissues of the body, particularly in those characterized by high proliferative activity, such as the bone marrow. The scenario is even more complex in the case of the central nervous system, and in particular brain tumors, where the blood brain barrier limits the efficacy of drug therapies. Integrins, transmembrane proteins widely expressed in different types of cancer (glioblastoma, melanoma, and breast cancer), regulate the angiogenic process and play a pivotal role in tumor growth and invasion. Here, we report a nanotechnology strategy based on the use of AuNPs decorated with an arginine-glycine-aspartic acid-like peptide for the diagnosis and treatment of cancer. Two hours after administration in mice, the accumulation of the peptide-decorated NPs in the subcutaneous tumor was ∼4-fold higher than that of uncoated particles and ∼1.4-fold higher than that of PEGylated particles. Also, in the case of the intracranial tumor model, interesting results were obtained. Indeed, 2 h after administration, the amount of peptide-decorated particles in the brain was 1.5-fold that of undecorated particles and 5-fold that of PEGylated particles. In conclusion, this preliminary study demonstrates the high potential of this carrier developed for diagnostic and therapeutic applications.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanomedicina/métodos , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Citometria de Fluxo , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Integrina alfaVbeta3/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Camundongos , Polietilenoglicóis/química
16.
Mol Pharm ; 16(6): 2569-2578, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31021643

RESUMO

In designing drug delivery systems with improved release properties and bioavailability, the dynamic features of the active pharmaceutical ingredient can be crucial for the final product properties. In this work, we aimed at obtaining the first characterization of the molecular dynamic properties of one of the most common nonsteroidal anti-inflammatory drug, ibuprofen, intercalated in hydrotalcite, an interesting inorganic carrier. By exploiting a variety of solid state NMR techniques, including 1H and 13C MAS spectra and T1 relaxation measurements, performed at variable temperature and carrying out a synergic analysis of all results, it has been possible to ascertain that the mobility of ibuprofen within the carrier is remarkably increased. In particular, strong indications have been obtained that ibuprofen molecules, in addition to internal interconformational dynamics, experience an overall molecular motion. Also considering that ibuprofen is "anchored" to the charged surface of the hydrotalcite layers through its carboxylate moiety, such motion could be a wobbling-in-a-cone. Activation energies and correlation times of all the motions of intercalated ibuprofen have been determined.


Assuntos
Ibuprofeno/química , Espectroscopia de Ressonância Magnética/métodos , Hidróxido de Alumínio/química , Hidróxido de Magnésio/química , Simulação de Dinâmica Molecular
17.
Pharmaceutics ; 10(4)2018 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-30558366

RESUMO

Pharmaceutical formulations suitable for dysphagic patients are not always commercially available, motivating caregivers to crush tablets or open capsules to facilitate swallowing. Since this action may modify the characteristics of the medicine, it should be considered potentially inappropriate. This paper is the first to focus on how hospitalization affected the rate of potentially inappropriate prescriptions (PIPs) and the incidence of dosage form-related PIPs in elderly patients with dysphagia. Data was collected by reviewing patient medical records in the Italian National Research Center on Aging of Ancona. The therapy at admission and discharge was analysed in terms of: inappropriate drug associations, inappropriate drugs for dysphagic patients, inappropriate dosage forms and inappropriate dosage form modifications. Forty-one dysphagic patients with an average age of 88.3 years were included in the study and 451 prescriptions were analysed. PIPs were widespread at admission, and hospitalization did not improve the situation in a statistically significant manner. The most common PIPs identified (>80%) were related to dosage form selection and modification. This study highlights a clear need for continuing medical education about prescription appropriateness and modification of solid dosage forms in patients with dysphagia.

18.
Front Pharmacol ; 9: 285, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29643808

RESUMO

Nanostructured lipid carriers (NLCs) loaded with palmitoylethanolamide (PEA) were formulated with the aim to enhance ocular bioavailability of PEA, particularly to the back of the eye. Technological characterization (e.g., size, charge) of NLC loaded with PEA formulation (PEA-NLC) was performed, and NLC morphology was characterized by electron microscopy. Ocular pharmacokinetic study, after topical administration of the formulation, was carried out in rabbit eye. Ultra-high performance liquid chromatography tandem mass spectrometry analysis was carried out to detect PEA levels in ocular tissues. Finally, the ocular tolerability of PEA-NLC formulation was assessed in rabbit eye. The novel formulation significantly increased PEA levels in ocular tissues compared to PEA suspension. Vitreous and retinal levels of PEA were significantly higher in the group treated with PEA-NLC formulation versus PEA suspension (PEA-NLC Cmax 5919 ± 541 pmol/g and 315 ± 70 pmol/g in vitreous and retina, respectively). The PEA-NLC formulation was characterized by high stability and robust ocular bioavailability. Therefore, this innovative formulation may be useful in clinical practice to manage retinal diseases.

19.
Artif Cells Nanomed Biotechnol ; 46(sup1): 219-229, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29265950

RESUMO

In recent decades, tissue engineering strategies have been proposed for the treatment of musculoskeletal diseases and bone fractures to overcome the limitations of the traditional surgical approaches based on allografts and autografts. In this work we report the development of a composite porous poly(dl-lactide-co-glycolide) scaffold suitable for bone regeneration. Scaffolds were produced by thermal sintering of porous microparticles. Next, in order to improve cell adhesion to the scaffold and subsequent proliferation, the scaffolds were coated with the osteoconductive biopolymers chitosan and sodium alginate, in a process that exploited electrostatic interactions between the positively charged biopolymers and the negatively charged PLGA scaffold. The resulting scaffolds were characterized in terms of porosity, degradation rate, mechanical properties, biocompatibility and suitability for bone regeneration. They were found to have an overall porosity of ∼85% and a degradation half time of ∼2 weeks, considered suitable to support de novo bone matrix deposition from mesenchymal stem cells. Histology confirmed the ability of the scaffold to sustain adipose-derived mesenchymal stem cell adhesion, infiltration, proliferation and osteo-differentiation. Histological staining of calcium and microanalysis confirmed the presence of calcium phosphate in the scaffold sections.


Assuntos
Fosfatos de Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Poliglactina 910/química , Poliglactina 910/farmacologia , Tecido Adiposo/citologia , Humanos , Fenômenos Mecânicos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Poliglactina 910/metabolismo , Porosidade
20.
J Sci Food Agric ; 98(7): 2824-2829, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29168202

RESUMO

BACKGROUND: Ecuador exports two major types of cocoa beans, the highly regarded and lucrative National, known for its fine aroma, and the CCN-51 clone type, used in bulk for mass chocolate products. In order to discourage exportation of National cocoa adulterated with CCN-51, a fast and objective methodology for distinguishing between the two types of cocoa beans is needed. RESULTS: This study reports a methodology based on computer vision, which makes it possible to recognize these beans and determine the percentage of their mixture. The methodology was challenged with 336 samples of National cocoa and 127 of CCN-51. By excluding the samples with a low fermentation level and white beans, the model discriminated with a precision higher than 98%. The model was also able to identify and quantify adulterations in 75 export batches of National cocoa and separate out poorly fermented beans. CONCLUSION: A scientifically reliable methodology able to discriminate between Ecuadorian National and CCN-51 cocoa beans and their mixtures was successfully developed. © 2017 Society of Chemical Industry.


Assuntos
Cacau/química , Cacau/classificação , Análise Discriminante , Equador , Fermentação , Sementes/química , Sementes/classificação
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