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OBJECTIVES: To evaluate the diagnostic performance in the assessment setting of three protocols: one-view wide-angle digital breast tomosynthesis (WA-DBT) with synthetic mammography (SM), two-view WA-DBT/SM, and two-view digital mammography (DM). METHODS: Included in this retrospective study were patients who underwent bilateral two-view DM and WA-DBT. SM were reconstructed from the WA-DBT data. The standard of reference was histology and/or 2 years follow-up. Included were 205 women with 179 lesions (89 malignant, 90 benign). Four blinded readers randomly evaluated images to assess density, lesion type, and level of suspicion according to BI-RADS. Three protocols were evaluated: two-view DM, one-view (mediolateral oblique) WA-DBT/SM, and two-view WA-DBT/SM. Detection rate, sensitivity, specificity, and accuracy were calculated and compared using multivariate analysis. Reading time was assessed. RESULTS: The detection rate was higher with two-view WA-DBT/SM (p = 0.063). Sensitivity was higher for two-view WA-DBT/SM compared to two-view DM (p = 0.001) and one-view WA-DBT/SM (p = 0.058). No significant differences in specificity were found. Accuracy was higher with both one-view WA-DBT/SM and two-view WA-DBT/SM compared to DM (p = 0.003 and > 0.001, respectively). Accuracy did not differ between one- and two-view WA-DBT/SM. Two-view WA-DBT/SM performed better for masses and asymmetries. Reading times were significantly longer when WA-DBT was evaluated. CONCLUSIONS: One-view and two-view WA-DBT/SM can achieve a higher diagnostic performance compared to two-view DM. The detection rate and sensitivity were highest with two-view WA-DBT/SM. Two-view WA-DBT/SM appears to be the most appropriate tool for the assessment of breast lesions. KEY POINTS: ⢠Detection rate with two-view wide-angle digital breast tomosynthesis (WA-DBT) is significantly higher than with two-view digital mammography in the assessment setting. ⢠Diagnostic accuracy of one-view and two-view WA-DBT with synthetic mammography (SM) in the assessment setting is higher than that of two-view digital mammography. ⢠Compared to one-view WA-DBT with SM, two-view WA-DBT with SM seems to be the most appropriate tool for the assessment of breast lesions.
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Neoplasias da Mama , Paraganglioma , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Feminino , Técnicas Histológicas , Humanos , Mamografia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.
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Anti-Inflamatórios não Esteroides/química , Inflamação/tratamento farmacológico , Piroxicam/química , Solubilidade/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/uso terapêutico , Etanol/química , Humanos , Piroxicam/uso terapêutico , Dióxido de Silício/química , Água/químicaRESUMO
Contrast-enhanced MRI (CE-MRI) is the most sensitive technique for breast cancer detection. Contrast-enhanced mammography (CEM) is emerging as a possible alternative to CE-MRI. PURPOSE: To evaluate the diagnostic performance of a low radiation dose contrast-enhanced mammography (L-CEM) in women with suspicious findings on conventional imaging compared to CE-MRI of the breast. STUDY TYPE: Prospective, single center. POPULATION: Women with suspicious findings on mammography, tomosynthesis, or ultrasound, and no contraindications for L-CEM or CE-MRI. Eighty women were included. FIELD STRENGTH/SEQUENCE: 1.5 and 3T CE-MRI, standard protocol for breast, with dedicated coils, according to international guidelines. L-CEM was performed using a dedicated prototype. ASSESSMENT: Three, off-site, blinded readers evaluated the images according to the BI-RADS lexicon in a randomized order, each in two separate reading sessions. Histology served as a gold standard. STATISTICAL TEST: Lesion detection rate, sensitivity, specificity, and negative and positive predictive values (NPV, PPV) were calculated and compared with multivariate statistics. RESULTS: Included were 80 women (mean age, 54.3 years ±11.2 standard deviation) with 93 lesions (32 benign, 61 malignant). The detection rate was significantly higher with CE-MRI (92.5-94.6%; L-CEM 79.6-91.4%, P = 0.014). Sensitivity (L-CEM 65.6-90.2%; CE-MRI 83.6-93.4%, P = 0.086) and NPV (L-CEM 59.6-71.4%; CE-MRI 63.0-76.5%, P = 0.780) did not differ between the modalities. Specificity (L-CEM 46.9-96.9%; CE-MRI 37.5-53.1%, P = 0.001) and PPV (L-CEM 76.4-97.6%; CE-MRI 73.3-77.3%, P = 0.007) were significantly higher with L-CEM. Variations between readers were significant for sensitivity and NPV. The accuracy of L-CEM was as good as CE-MRI (75.3-76.3% vs. 72.0-75.3%, P = 0.514). DATA CONCLUSION: L-CEM showed a high sensitivity and accuracy in women with suspicious findings on conventional imaging. Compared to CE-MRI, L-CEM has the potential to increase specificity and PPV. L-CEM might help to reduce false-positive biopsies while obtaining sensitivity comparable to that of CE-MRI LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:589-595.
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Neoplasias da Mama , Meios de Contraste , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Imageamento por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
The yeast Pichia fermentans DISAABA 726 strain (P. fermentans) is a dimorphic yeast that under different environmental conditions may switch from a yeast-like to pseudohyphal morphology. We hypothesize that exosomes-like vesicles (EV) could mediate this rapid modification. EV are membrane-derived vesicles carrying lipids, proteins, mRNAs and microRNAs and have been recognized as important mediators of intercellular communication. Although it has been assumed for a long time that fungi release EV, knowledge of their functions is still limited. In this work we analyze P. fermentans EV production during growth in two different media containing urea (YCU) or methionine (YCM) where yeast-like or pseudohyphal morphology are produced. We developed a procedure to extract EV from the neighboring biofilm which is faster and more efficient as compared to the widely used ultracentrifugation method. Differences in morphology and RNA content of EV suggest that they might have an active role during dimorphic transition as response to the growth conditions. Our findings are coherent with a general state of hypoxic stress of the pseudohyphal cells.
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Biofilmes , Vesículas Extracelulares/metabolismo , Pichia/fisiologia , Meios de Cultura , Vesículas Extracelulares/ultraestrutura , Proteínas Fúngicas/metabolismo , MicroRNAs/metabolismo , Viabilidade Microbiana , Pichia/citologia , Pichia/ultraestrutura , RNA Fúngico/metabolismoRESUMO
Invited for this month's cover are the collaborating groups of Prof. Serena Riela at University of Catania, Prof. César Viseras at University of Granada and Dr. Ignacio Sainz-Diaz at Instituto Andaluz de Ciencias de la Tierra. The cover picture shows the possible application of the developed system. In particular, flufenamic acid, anti-inflammatory and anti-pyretic drug, was complexed into cucurbituril cavity and the supramolecular system obtained was used as filler for laponite® hydrogel for its topical delivery. More information can be found in the Research Article by Viseras-Iborra, Riela, and co-workers.
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Ácido Flufenâmico , Compostos Macrocíclicos , Silicatos , Humanos , HidrogéisRESUMO
Nowadays the use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on Laponite® (Lap) clay mineral as gelator and cucurbit[6]uril (CB[6]) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application. Firstly, the interaction between CB[6] and FFA was assessed by UV-vis spectroscopic measurements and molecular modeling calculations. Then, the obtained complex was used as filler for Lap hydrogel (Lap/CB[6]/FFA). The properties of the hydrogel in terms of viscosity and, self-repair abilities were investigated; its morphology was imaged by scanning electron and polarized optical microscopies. Furthermore, the changes in the hydrodynamic radii and in the colloidal stability of CB[6]/Lap mixture were investigated in terms of translational diffusion from dynamic light scattering and ζ-potential measurements. Finally, the kinetic inâ vitro release of FFA, from Lap/CB[6]/FFA hydrogel, was studied in a medium mimicking the pH of skin and the obtained results were discussed both by an experimental point of view and by molecular modeling calculations.
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Sistemas de Liberação de Medicamentos , Hidrogéis , Hidrogéis/química , Sistemas de Liberação de Medicamentos/métodos , Silicatos/químicaRESUMO
Bacterial infections represent one of the major causes of mortality worldwide. Therefore, over the years, several nanomaterials with antibacterial properties have been developed. In this context, clay minerals, because of their intrinsic properties, have been efficiently used as antimicrobial agents since ancient times. Halloysite nanotubes are one of the emerging nanomaterials that have found application as antimicrobial agents in several fields. In this review, we summarize some examples of the use of pristine and modified halloysite nanotubes as antimicrobial agents, scaffolds for wound healing and orthopedic implants, fillers for active food packaging, and carriers for pesticides in food pest control.
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Objective: To compare two strategies [the neonatal sepsis risk calculator (NSC) and the updated serial clinical observation approach (SCO)] for the management of asymptomatic neonates at risk of early-onset sepsis (EOS) and neonates with mild non-progressive symptoms in the first hours of life. Methods: This was a single-center, retrospective cohort study conducted over 15 months (01/01/2019-31/03/2020). All live births at ≥34 weeks of gestation were included. Infants were managed using SCO and decisions were compared with those retrospectively projected by the NSC. The proportion of infants recommended for antibiotics or laboratory testing was compared in both strategies. McNemar's non-parametric test was used to assess significant differences in matched proportions. Results: Among the 3,445 neonates (late-preterm, n = 178; full-term, n = 3,267) 262 (7.6%) presented with symptoms of suspected EOS. There were no cases of culture-proven EOS. Only 1.9% of the neonates were treated with antibiotics (median antibiotic treatment, 2 days) and 4.0% were evaluated. According to NSC, antibiotics would have been administered in 5.4% of infants (absolute difference between SCO and NSC, 3.51%; 95% CI, 3.14-3.71%; p <0.0001) and 5.6% of infants would have undergone "rule out sepsis" (absolute difference between SCO and NSC, 1.63%, 95% CI 1.10-2.05; p <0.0001). Conclusion: SCO minimizes laboratory testing and unnecessary antibiotics in infants at risk of EOS or with mild non-progressive symptoms, without the risk of a worse neonatal outcome. The NSC recommends almost three times more antibiotics than the SCO without improving neonatal outcomes.
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Objective: This study aims to evaluate safety and success rates of lumbar puncture (LP) and to identify factors associated with adverse events or failure of LP in infants. Methods: This two-center prospective observational study investigated infants younger than 90 days of age who underwent LP. Need for resuscitation oxygen desaturation (SpO2 < 90%), bradycardia and intraventricular hemorrhage were considered adverse events. LP failed if cerebrospinal spinal fluid was not collected or had traces of blood. Logistic regression analysis was used to evaluate whether corrected gestational age (GA), body weight at LP, position, and any respiratory support during LP affected SpO2 desaturation or failure of LP. Results: Among 204 LPs, 134 were performed in full-term and 70 in pre-term born infants. SpO2 desaturations occurred during 45 (22.4%) LPs. At multivariate analysis, lower GA at LP (p < 0.001), non-invasive respiratory support (p 0.007) and mechanical ventilation (p 0.004) were associated with SpO2 desaturations. Transient, self-resolving bradycardia occurred in 7 (3.4%) infants. Two infants had intraventricular hemorrhage detected within 72 h of LP. No further adverse events were registered. Failure of LP occurred in 38.2% of cases and was not associated with any of the factors evaluated. Conclusions: LP was safe in most infants. Body weight or GA at LP did not affect LP failure. These data are useful to clinicians, providing information on the safety of the procedure.
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OBJECTIVES: The aim of this study was to evaluate the detection rate and diagnostic performance of 2-dimensional synthetic mammography (SM) as an adjunct to wide-angle digital breast tomosynthesis (WA-DBT) compared with digital mammography (DM) alone or to DM in combination with WA-DBT. MATERIALS AND METHODS: There were 205 women with 179 lesions included in this retrospective reader study. Patients underwent bilateral, 2-view (2v) DM and WA-DBT between March and June 2015. The standard of reference was histology and/or 1-year stability at follow-up. Four blinded readers randomly evaluated images according to the BI-RADS lexicon from 3 different protocols: 2v DM alone, 2v DM with 2v WA-DBT, and 2v SM with 2v WA-DBT. Detection rate, sensitivity, specificity, and accuracy were calculated and compared using multivariate analysis. Readers' confidence and image quality were evaluated. RESULTS: The detection rate ranged from 68.7% to 79.9% for DM, 76.5% to 84.4% for DM with WA-DBT, and 73.2% to 84.9% for SM with WA-DBT. Sensitivity and accuracy were significantly higher when DBT was available (P < 0.001). Specificity did not differ significantly between DM only, DM with WA-DBT, or SM with WA-DBT (P ≥ 0.846). Wide-angle DBT combined readings did not differ between SM and DM in terms of sensitivity, specificity, and accuracy (P ≥ 0.341). Readers' confidence and image quality was rated good to excellent. CONCLUSIONS: Wide-angle DBT combined with DM or SM increases sensitivity and accuracy without reducing specificity compared with DM alone. Wide-angle DBT combined readings did not differ between SM and DM; therefore, SM should replace DM for combined readings with WA-DBT.
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Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Supercritical solvent impregnation (SSI) is a green unconventional technique for preparing amorphous drug formulations. A mesoporous nanostructured ZnO (mesoNsZnO) carrier with 8-nm pores, spherical-nanoparticle morphology, and an SSA of 75 m2/g has been synthesized and, for the first time, subjected to SSI with poorly water-soluble drugs. Ibuprofen (IBU), clotrimazole (CTZ), and hydrocortisone (HC) were selected as highly, moderately, and poorly CO2-soluble drugs. Powder X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, nitrogen adsorption analysis, and ethanol extraction coupled with ultraviolet spectroscopy were employed to characterize the samples and quantify drug loading. Successful results were obtained with IBU and CTZ while HC loading was negligible, which could be related to different solubilities in CO2, drug size, and polarity. Successful SSI resulted in amorphous multilayer confinement of the drug. The mesoNsZnO-IBU system showed double drug loading than the mesoNsZnO-CTZ one, with a maximum uptake of 0.24 g/g. Variation of contact time during SSI of the mesoNsZnO-IBU system showed that drug loading triplicated between 3 and 8 h with an additional 30% increment between 8 h and 24 h. SSI did not affect the mesoNsZnO structure, and the presence of the adsorbed drug reduced the chemisorption of CO2 on the carrier surface.
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In situ forming hydrogels are a class of biomaterials that can fulfil a variety of important biomedically relevant functions and hold promise for the emerging field of patient-specific treatments (e.g., cell therapy, drug delivery). Here we report the results of our investigations on the generation of in situ forming hydrogels with potential for wound healing applications (e.g., complex blast injuries). The combination of polysaccharides that were oxidized to display aldehydes, amine displaying chitosan and nanostructured ZnO yields in situ forming bionanocomposite hydrogels. The physicochemical properties of the components, their cytotoxicity towards HaCat cells and the in vitro release of zinc ions on synthetic skin were studied. The in situ gel formation process was complete within minutes, the components were non-toxic towards HaCat cells at functional levels, Zn2+ was released from the gels, and such materials may facilitate wound healing.
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The physicoâ»chemical and biological properties of nanostructured ZnO are combined with the non-toxic and eco-friendly features of the scCO2-mediated drug loading technique to develop a multifunctional antimicrobial drug delivery system for potential applications in wound healing. Two nanostructured ZnO (NsZnO) with different morphologies were prepared through wet organic-solvent-free processes and characterized by means of powder X-ray diffraction, field emission scanning electron microscopy (FESEM), and nitrogen adsorption analysis. The antimicrobial activity of the two samples against different microbial strains was investigated together with the in vitro Zn2+ release. The results indicated that the two ZnO nanostructures exhibited the following activity: S. aureus > C. albicans > K. pneumoniae. A correlation between the antimicrobial activity, the physicoâ»chemical properties (specific surface area and crystal size) and the Zn2+ ion release was found. Ibuprofen was, for the first time, loaded on the NsZnO carriers with a supercritical CO2-mediated drug impregnation process and in vitro dissolution studies of the loaded drug were performed. A successful loading up to 14% w/w of ibuprofen in its amorphous form was obtained. A preliminary drug release test showed that up to 68% of the loaded ibuprofen could be delivered to a biological medium, confirming the feasibility of using NsZnO as a multifunctional antimicrobial drug carrier.
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Acyclovir is not a good candidate for passive permeation since its polarity and solubility limit is partitioning into the stratum corneum. This work aims to develop a new topical formulation for the acyclovir delivery. New chitosan nanospheres (NS) were prepared by a modified nano-emulsion template method. Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and an in vitro release study. The in vitro skin permeation experiment was carried out using Franz cells and was equipped with porcine skin. Biological studies were performed on the Vero cell line infected by HSV-1 and HSV-2 strains. The acyclovir loaded chitosan NS appeared with a spherical shape, a size of about 200 nm, and a negative zeta potential of about 40.0 mV. The loading capacity of the drug was about 8.5%. In vitro release demonstrated that the percentage of acyclovir delivered from the nanospheres was approximately 30% after six hours. The in vitro skin permeation studies confirmed an improved amount of permeated acyclovir. The acyclovir-NS complex displayed a higher antiviral activity than that of free acyclovir against both the HSV-1 and the HSV-2 strain. The acyclovir-loaded NS showed no anti-proliferative activity and no signs of cytotoxicity induced by NS was detected. Confocal laser scanning microscopy confirmed that the NS are taken up by the cells.
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This work deals with the synthesis and characterization of novel Fe-containing sol-gel materials obtained by modifying the composition of a binary SiO2-CaO parent glass with the addition of Fe2O3. The effect of different processing conditions (calcination in air vs. argon flowing) on the formation of magnetic crystalline phases was investigated. The produced materials were analyzed from thermal (hot-stage microscopy, differential thermal analysis, and differential thermal calorimetry) and microstructural (X-ray diffraction) viewpoints to assess both the behavior upon heating and the development of crystalline phases. N2 adsorption-desorption measurements allowed determining that these materials have high surface area (40-120 m²/g) and mesoporous texture with mesopore size in the range of 18 to 30 nm. It was assessed that the magnetic properties can actually be tailored by controlling the Fe content and the environmental conditions (oxidant vs. inert atmosphere) during calcination. The glasses and glass-ceramics developed in this work show promise for applications in bone tissue healing which require the use of biocompatible magnetic implants able to elicit therapeutic actions, such as hyperthermia for bone cancer treatment.
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Drug delivery by means of transdermal patches raised great interest as a non-invasive and sustained therapy. The present research aimed to design a patch for transdermal delivery of melatonin, which was encapsulated in polycaprolactone (PCL) nanoparticles (NPs) by employing flash nanoprecipitation (FNP) technique. Melatonin-loaded PCL nanoparticles were successfully prepared with precise control of the particle size by effectively tuning process parameters. The effect of process parameters on the particle size was assessed by dynamic light scattering for producing particles with suitable size for transdermal applications. Quantification of encapsulated melatonin was performed by mean of UV spectrophotometry, obtaining the estimation of encapsulation efficiency (EE%) and loading capacity (LC%). An EE% higher than 80% was obtained. Differential scanning calorimetry (DSC) analysis of NPs was performed to confirm effective encapsulation in the solid phase. Cotton fabrics, functionalized by imbibition with the nano-suspension, were analyzed by scanning electron microscopy to check morphology, adhesion and distribution of the NPs on the surface; melatonin transdermal release from the functionalized fabric was performed via Franz's cells by using a synthetic membrane. NPs were uniformly distributed on cotton fibres, as confirmed by SEM observations; the release test showed a continuous and controlled release whose kinetics were satisfactorily described by Baker-Lonsdale model.
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INTRODUCTION: A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bottom-up and top-down methods or by their combination. They have been designed to enhance the solubility, the dissolution rate and the bioavailability of drugs via various administration routes. Due to their small sizes, nanosuspensions can be also considered a drug delivery nanotechnology for the preparation of nanomedicine products. AREAS COVERED: This review focuses on the state of the art of the nanocrystal-based formulation. It describes theory characteristics, design parameters, preparation methods, stability issues, as well as specific in vivo applications. Innovative strategies proposed to obtain nanomedicine formulation using nanocrystals are also reported. EXPERT OPINION: Many drug nanodelivery systems have been developed to increase the bioavailability of drugs and to decrease adverse side effects, but few can be industrially manufactured. Nanocrystals can close this gap by combining traditional and innovative drug formulations. Indeed, they can be used in many pharmaceutical dosage forms as such, or developed as new nano-scaled products. Engineered surface nanocrystals have recently been proposed as a dual strategy for stability enhancement and targeting delivery of nanocrystals.
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Química Farmacêutica , Nanopartículas/química , Suspensões , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nanotecnologia/métodos , Solubilidade , TensoativosRESUMO
The aim of this work was to develop new chitosan nanospheres for the delivery of 5-fluorouracil (5-FU). Drug loaded nanospheres were prepared using a technique derived from a combination of coacervation and emulsion droplet coalescence methods. The size and morphology of nanospheres were characterized by laser light scattering and transmission electron microscopy. The 5-FU interaction with chitosan nanospheres was investigated by DSC analysis and FT-IR spectroscopy. The in vitro release was studied by dialysis bag technique. Cytotoxicity of 5-FU loaded chitosan nanospheres was evaluated in vitro on HT29 and PC-3 cell lines. The effects of 5-FU loaded chitosan nanospheres on adhesion of tumor cells to human umbilical vein endothelial cells (HUVEC) were also investigated. 5-FU loaded chitosan nanospheres appeared with a spherical shape, with a mean diameter of about 200 nm and a negative zeta potential of about - 6.0 mV. The successful interaction between drug and chitosan nanosphere matrix was demonstrated by both DSC and FT-IR analyses. The quantitative determination of 5-FU was assayed by UV-Vis analysis. The encapsulation efficiency of 5-FU content was about 70%. A kinetic study of in vitro release demonstrated that the percentages of 5-FU delivered from nanospheres was approx. 10% after 3 hours. The in vitro studies showed that 5-FU loaded nanospheres were effective in reducing tumor cell proliferation in a time- and concentration-dependent manner. 5-FU nanospheres were also able to inhibit both HT29 and PC-3 adhesion to HUVEC after 48 hours of treatment.