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3.
Proteomics ; 24(5): e2300145, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37726251

RESUMO

Exact p-value (XPV)-based methods for dot product-like score functions-such as the XCorr score implemented in Tide, SEQUEST, Comet or shared peak count-based scoring in MSGF+ and ASPV-provide a fairly good calibration for peptide-spectrum-match (PSM) scoring in database searching-based MS/MS spectrum data identification. Unfortunately, standard XPV methods, in practice, cannot handle high-resolution fragmentation data produced by state-of-the-art mass spectrometers because having smaller bins increases the number of fragment matches that are assigned to incorrect bins and scored improperly. In this article, we present an extension of the XPV method, called the high-resolution exact p-value (HR-XPV) method, which can be used to calibrate PSM scores of high-resolution MS/MS spectra obtained with dot product-like scoring such as the XCorr. The HR-XPV carries remainder masses throughout the fragmentation, allowing them to greatly increase the number of fragments that are properly assigned to the correct bin and, thus, taking advantage of high-resolution data. Using four mass spectrometry data sets, our experimental results demonstrate that HR-XPV produces well-calibrated scores, which in turn results in more trusted spectrum annotations at any false discovery rate level.


Assuntos
Algoritmos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Software , Peptídeos/química , Calibragem , Bases de Dados de Proteínas
4.
Front Surg ; 10: 1282937, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026483

RESUMO

Introduction: Patients undergoing thoracic surgery are at increased risk of developing, long-lasting pain. Beyond the non-surgical factors, the type of operation, including the number of incisions, and the anesthetic assessment seemed to be important factors, although some studies are controversial. The aim of our study was to examine the presence of chronic postoperative pain after non-intubated uniportal VATS lobectomy. We examined the difference between the intubated, relaxed and non-intubated spontaneous ventilation surgical approaches in patients who underwent video-assisted thoracoscopic (VATS) uniportal lobectomy. Methods: Demographic and postoperative data were retrospectively collected and analyzed, focusing on the use of pain medications, in 67 patients of the 140 patients selected by propensity score matching who underwent intubated (iVATS) or non-intubated (NITS) uniportal VATS lobectomy. This study focused on the use of analgesic medications 3, 6, and 12 months after surgery. Results: Thirty-five intubated and 32 non-intubated patients were compared. Although the analgesic consumption was nearly 2% higher among the iVATS patients during the follow-up period, there were no statistically significant differences at 3 months (15.6 vs. 17.1%) (p = 0.868), at 6 months (9.4 vs. 12.4%) (p = 0.785), and at 12 months (3.3 vs. 5.9%) (p = 0.633) between the NITS and iVATS groups, respectively. More female than male patients reported chronic pain, but the difference was not statistically significant (p = 0.616). Diabetes mellitus was a statistically significant cofactor associated with chronic pain (p = 0.03), while cardiac disease (p = 0.6), perioperative morbidity (p = 0.228), prolonged air leak (p = 0.057), and repeat drainage (p = 0.626) were not. Conclusion: Our study suggests that after non-intubation VATS lobectomies, the postoperative pain was less at 3, 6, and 12 months in NITS patients compared to iVATS patients. The 2% difference was not significant, so it may not be appropriate to claim the advantages of NITS in terms of postoperative pain.

5.
J Clin Med ; 12(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37892595

RESUMO

BACKGROUND: Non-intubated thoracic surgery has not achieved widespread acceptance despite its potential to improve postoperative outcomes. To ensure airway safety, our institute has developed a technique combining spontaneous ventilation with double-lumen tube intubation (SVI). This study aimed to verify the feasibility and limitations of this SVI technique. METHODS: For the SVI method, anesthesia induction involves fentanyl and propofol target-controlled infusion, with mivacurium administration. Bispectral index monitoring was used to ensure the optimal depth of anesthesia. Short-term muscle relaxation facilitated double-lumen tube intubation and early surgical steps. Chest opening preceded local infiltration, followed by a vagal nerve blockade to prevent the cough reflex and a paravertebral blockade for pain relief. Subsequently, the muscle relaxant was ceased. The patient underwent spontaneous breathing without coughing during surgical manipulation. RESULTS: Between 10 March 2020 and 28 October 2022, 141 SVI surgeries were performed. Spontaneous respiration with positive end-expiratory pressure was sufficient in 65.96% (93/141) of cases, whereas 31.21% (44/141) required pressure support ventilation. Only 2.84% (4/141) of cases reversed to conventional anesthetic management, owing to technical or surgical difficulties. Results of the 141 cases: The mean maximal carbon dioxide pressure was 59.01 (34.4-92.9) mmHg, and the mean lowest oxygen saturation was 93.96% (81-100%). The mean one-lung, mechanical and spontaneous one-lung ventilation time was 74.88 (20-140), 17.55 (0-115) and 57.73 (0-130) min, respectively. CONCLUSIONS: Spontaneous ventilation with double-lumen tube intubation is safe and feasible for thoracic surgery. The mechanical one-lung ventilation time was reduced by 76.5%, and the rate of anesthetic conversion to relaxation was low (2.8%).

6.
Orv Hetil ; 164(37): 1476-1483, 2023 Sep 17.
Artigo em Húngaro | MEDLINE | ID: mdl-37717235

RESUMO

Castleman disease is an uncommon lymphoproliferative disorder, located most commonly in the mediastinal lymph nodes. The intrapulmonary presentation is extremely rare, with 14 published cases in the English literature. The clinical presentation of the disorder is not specific and the diagnosis is often challenging. The main goal is to achieve an R0 surgical resection which gives the potential chance for a recurrence-free survival. We present the case of a symptomless, 15-year-old female patient with left-sided tumor mass. Transthoracal invasive tissue biopsy confirmed Castleman disease. The central mass involved the main structures in the left hilus and therefore left pulmonectomy was necessary to reach the complete, tumor-free resection margins. The patient had no local or distant relapse during the 7-year follow-up. Although Castleman disease treated by complete surgical resection provides excellent results, radical and extended lung resection is sometimes inevitable to reach tumor-free margins. Orv Hetil. 2023; 164(37): 1476-1483.


Assuntos
Hiperplasia do Linfonodo Gigante , Pneumonectomia , Feminino , Humanos , Adolescente , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/cirurgia , Linfonodos , Biópsia
7.
Acta Neuropathol Commun ; 11(1): 155, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749707

RESUMO

Inflammasomes, primarily responsible for the activation of IL-1ß, have emerged as critical regulators of the tumor microenvironment. By using in vivo and in vitro brain metastasis models, as well as human samples to study the role of the NLRP3 inflammasome in triple-negative breast cancer (TNBC) brain metastases, we found NLRP3 inflammasome components and IL-1ß to be highly and specifically expressed in peritumoral astrocytes. Soluble factors from TNBC cells induced upregulation and activation of NLRP3 and IL-1ß in astrocytes, while astrocyte-derived mediators augmented the proliferation of metastatic cells. In addition, inhibition of NLRP3 inflammasome activity using MCC950 or dampening the downstream effect of IL-1ß prevented the proliferation increase in cancer cells. In vivo, MCC950 reduced IL-1ß expression in peritumoral astrocytes, as well as the levels of inflammasome components and active IL-1ß. Most importantly, significantly retarded growth of brain metastatic tumors was observed in mice treated with MCC950. Overall, astrocytes contribute to TNBC progression in the brain through activation of the NLRP3 inflammasome and consequent IL-1ß release. We conclude that pharmacological targeting of inflammasomes may become a novel strategy in controlling brain metastatic diseases.


Assuntos
Neoplasias Encefálicas , Indenos , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Inflamassomos , Astrócitos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sulfonamidas/farmacologia , Microambiente Tumoral
8.
Cell Mol Life Sci ; 80(7): 192, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380797

RESUMO

Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to the limited access to functional human ductal epithelia. Patient-derived organoids may overcome these limitations, however direct accessibility of the apical membrane is not solved. In addition, due to the vectorial transport of ions and fluid the intraluminal pressure in the organoids is elevated, which may hinder the study of physiological processes. To overcome these, we developed an advanced culturing method for human pancreatic organoids based on the removal of the extracellular matrix that induced an apical-to-basal polarity switch also leading to reversed localization of proteins with polarized expression. The cells in the apical-out organoids had a cuboidal shape, whereas their resting intracellular Ca2+ concentration was more consistent compared to the cells in the apical-in organoids. Using this advanced model, we demonstrated the expression and function of two novel ion channels, the Ca2+ activated Cl- channel Anoctamin 1 (ANO1) and the epithelial Na+ channel (ENaC), which were not considered in ductal cells yet. Finally, we showed that the available functional assays, such as forskolin-induced swelling, or intracellular Cl- measurement have improved dynamic range when performed with apical-out organoids. Taken together our data suggest that polarity-switched human pancreatic ductal organoids are suitable models to expand our toolset in basic and translational research.


Assuntos
Células Epiteliais , Pâncreas , Humanos , Fígado , Epitélio , Bioensaio
9.
J Proteome Res ; 22(2): 577-584, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36633229

RESUMO

The first step in the analysis of protein tandem mass spectrometry data typically involves searching the observed spectra against a protein database. During database search, the search engine must digest the proteins in the database into peptides, subject to digestion rules that are under user control. The choice of these digestion parameters, as well as selection of post-translational modifications (PTMs), can dramatically affect the size of the search space and hence the statistical power of the search. The Tide search engine separates the creation of the peptide index from the database search step, thereby saving time by allowing a peptide index to be reused in multiple searches. Here we describe an improved implementation of the indexing component of Tide that consumes around four times less resources (CPU and RAM) than the previous version and can generate arbitrarily large peptide databases, limited by only the amount of available disk space. We use this improved implementation to explore the relationship between database size and the parameters controlling digestion and PTMs, as well as database size and statistical power. Our results can help guide practitioners in proper selection of these important parameters.


Assuntos
Algoritmos , Peptídeos , Peptídeos/química , Proteínas/metabolismo , Ferramenta de Busca , Bases de Dados de Proteínas , Software
10.
Inorg Chem ; 61(36): 14403-14418, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36044722

RESUMO

Research on new reaction routes and precursors to prepare catalysts for CO2 hydrogenation has enormous importance. Here, we report on the preparation of the permanganate salt of the urea-coordinated iron(III), [hexakis(urea-O)iron(III)]permanganate ([Fe(urea-O)6](MnO4)3) via an affordable synthesis route and preliminarily demonstrate the catalytic activity of its (Fe,Mn)Ox thermal decomposition products in CO2 hydrogenation. [Fe(urea-O)6](MnO4)3 contains O-coordinated urea ligands in octahedral propeller-like arrangement around the Fe3+ cation. There are extended hydrogen bond interactions between the permanganate ions and the hydrogen atoms of the urea ligands. These hydrogen bonds serve as reaction centers and have unique roles in the solid-phase quasi-intramolecular redox reaction of the urea ligand and the permanganate anion below the temperature of ligand loss of the complex cation. The decomposition mechanism of the urea ligand (ammonia elimination with the formation of isocyanuric acid and biuret) has been clarified. In an inert atmosphere, the final thermal decomposition product was manganese-containing wuestite, (Fe,Mn)O, at 800 °C, whereas in ambient air, two types of bixbyite (Fe,Mn)2O3 as well as jacobsite (Fe,Mn)T-4(Fe,Mn)OC-62O4), with overall Fe to Mn stoichiometry of 1:3, were formed. These final products were obtained regardless of the different atmospheres applied during thermal treatments up to 350 °C. Disordered bixbyite formed first with inhomogeneous Fe and Mn distribution and double-size supercell and then transformed gradually into common bixbyite with regular structure (and with 1:3 Fe to Mn ratio) upon increasing the temperature and heating time. The (Fe,Mn)Ox intermediates formed under various conditions showed catalytic effect in the CO2 hydrogenation reaction with <57.6% CO2 conversions and <39.3% hydrocarbon yields. As a mild solid-phase oxidant, hexakis(urea-O)iron(III) permanganate, was found to be selective in the transformation of (un)substituted benzylic alcohols into benzaldehydes and benzonitriles.

11.
J Cereb Blood Flow Metab ; 42(4): 584-599, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34427145

RESUMO

Spreading depolarizations (SDs) indicate injury progression and predict worse clinical outcome in acute brain injury. We demonstrate in rodents that acute brain swelling upon cerebral ischemia impairs astroglial glutamate clearance and increases the tissue area invaded by SD. The cytotoxic extracellular glutamate accumulation (>15 µM) predisposes an extensive bulk of tissue (4-5 mm2) for a yet undescribed simultaneous depolarization (SiD). We confirm in rat brain slices exposed to osmotic stress that SiD is the pathological expansion of prior punctual SD foci (0.5-1 mm2), is associated with astrocyte swelling, and triggers oncotic neuron death. The blockade of astrocytic aquaporin-4 channels and Na+/K+/Cl- co-transporters, or volume-regulated anion channels mitigated slice edema, extracellular glutamate accumulation (<10 µM) and SiD occurrence. Reversal of slice swelling by hyperosmotic mannitol counteracted glutamate accumulation and prevented SiD. In contrast, inhibition of glial metabolism or inhibition of astrocyte glutamate transporters reproduced the SiD phenotype. Finally, we show in the rodent water intoxication model of cytotoxic edema that astrocyte swelling and altered astrocyte calcium waves are central in the evolution of SiD. We discuss our results in the light of evidence for SiD in the human cortex. Our results emphasize the need of preventive osmotherapy in acute brain injury.


Assuntos
Edema Encefálico , Lesões Encefálicas , Animais , Ratos , Astrócitos/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas/metabolismo , Edema/metabolismo , Ácido Glutâmico/metabolismo , Simportadores de Cloreto de Sódio-Potássio/metabolismo
12.
Int J Pharm ; 611: 121327, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34852289

RESUMO

Curcuminoids (CUs) of antitumor and various other potential biological activities have extremely low water solubility therefore special formulation was elaborated. New fast dissolving reconstitution dosage forms of four CUs were prepared as fibrous form of 2-hydroxypropyl-ß-cyclodextin (HP-ß-CD). In the electrospinning process HP-ß-CD could act both as solubilizer and fiber-forming agent. The solubilization efficiency of the CU-HP-ß-CD systems was determined with phase-solubility measurements. The electrospun CUs were amorphous and uniformly distributed in the fibers according to XRD analysis and Raman mappings. The fibrous final products had fast (<5 min) and complete dissolution. In typical iv. infusion reconstitution volume (20 mL) fibers containing 40-80 mg of CU could be dissolved, which is similar to the currently proposed dose (<120 mg/m2). The in vitro cytostatic effect data showed that the antitumor activity of the CU-HP-ß-CD complexes was similar or better compared to the free APIs.


Assuntos
Diarileptanoides , Neoplasias , Excipientes , Humanos , Derivados da Hipromelose , Neoplasias/tratamento farmacológico , Solubilidade
13.
J Proteome Res ; 20(10): 4708-4717, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449232

RESUMO

Spectrum annotation is a challenging task due to the presence of unexpected peptide fragmentation ions as well as the inaccuracy of the detectors of the spectrometers. We present a deep convolutional neural network, called Slider, which learns an optimal feature extraction in its kernels for scoring mass spectrometry (MS)/MS spectra to increase the number of spectrum annotations with high confidence. Experimental results using publicly available data sets show that Slider can annotate slightly more spectra than the state-of-the-art methods (BoltzMatch, Res-EV, Prosit), albeit 2-10 times faster. More interestingly, Slider provides only 2-4% fewer spectrum annotations with low-resolution fragmentation information than other methods with high-resolution information. This means that Slider can exploit nearly as much information from the context of low-resolution spectrum peaks as the high-resolution fragmentation information can provide for other scoring methods. Thus, Slider can be an optimal choice for practitioners using old spectrometers with low-resolution detectors.


Assuntos
Redes Neurais de Computação , Espectrometria de Massas em Tandem , Algoritmos , Bases de Dados Factuais , Peptídeos
14.
Materials (Basel) ; 14(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201568

RESUMO

In this paper we report the synthesis of a N, S co-doped metal free carbon cryogel obtained from a marine biomass derived precursor using urea as nitrogen source. Natural carrageenan intrinsically contains S and inorganic salt. The latter also serves as an activating agent during the pyrolytic step. The overall 11.6 atomic % surface heteroatom concentration comprises 5% O, 4.6% N and 1% S. The purified and annealed final carbon (CA) has a hierarchical pore structure of micro-, meso- and macropores with an apparent surface area of 1070 m2/g. No further treatment was applied. The gas adsorption potential of the samples was probed with H2, CO2 and CH4, while the electrocatalytic properties were tested in an oxygen reduction reaction. The atmospheric CO2 and CH4 storage capacity at 0 °C in the low pressure range is very similar to that of HKUST-1, with the CO2/CH4 selectivity below 20 bar, even exceeding that of the MOF, indicating the potential of CA in biogas separation. The electrocatalytic behavior was assessed in an aqueous KOH medium. The observed specific gravimetric capacitance 377 F/g was exceeded only in B, N dual doped and/or graphene doped carbons from among metal free electrode materials. The CA electrode displays almost the same performance as a commercial 20 wt% Pt/C electrode. The oxygen reduction reaction (ORR) exhibits the 4-electron mechanism. The 500-cycle preliminary stability test showed only a slight increase of the surface charge.

15.
Carbohydr Polym ; 264: 118011, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33910715

RESUMO

Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement. Complete amorphousness of the cyclodextrin-enabled REM formulation was demonstrated by X-ray diffraction, thermal analysis, Raman chemical mapping and electron microscopy/energy dispersive spectroscopy. The use of solubilizing carbohydrate resulted in a 300-fold improvement of the aqueous solubility of REM, and enhanced dissolution rate of the drug enabling the preparation of stable infusion solutions for therapy. 2D ROESY NMR spectroscopy provided information on the nature of REM-excipient interaction and indicated the presence of inclusion phenomenon and the electrostatic attraction between anionic SBECD and nitrogen-containing REM in aqueous solution.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Excipientes/química , beta-Ciclodextrinas/química , Monofosfato de Adenosina/química , Alanina/química , Antivirais/química , Varredura Diferencial de Calorimetria , Liofilização/métodos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Simulação de Acoplamento Molecular , Nanofibras/química , Pós , Solubilidade , Análise Espectral Raman , Difração de Raios X , Tratamento Farmacológico da COVID-19
16.
Magy Seb ; 73(4): 125-139, 2020 Dec 12.
Artigo em Húngaro | MEDLINE | ID: mdl-33310915

RESUMO

Introduction: Surgical technique of thymectomy performed for treatment of myasthenia gravis has considerably changed in the last almost 30 years. In addition to standard interventions ­ transsternal and transcervical thymectomy ­, video-assisted thoracoscopic interventions (VATS), later on robotic surgery came into general use. In our two institutions, we apply VATS thymectomy since 2011. Methods: There are several different surgical techniques for this purpose; we approached the mediastinum through the right thoracic cavity. We prepared initially 3, later on 2 perimammal ports for the access of the thymus; the patients were in supine position during surgery. We used an ultrasonic cutting device in all cases. In order to perform extended thymectomy, we removed the fatty tissue around the thymus and opened widely the left thoracic cavity, too. During patient enrollment, we preferred patients with normal or lower body weight. Results: During 8 years and 4 months, we operated on 92 patients using this method for myasthenia gravis without thymoma; there were 20 male and 72 female patients at the age of 33 years on average (19­75 years). Duration of surgery was 35­160 minutes, 82.3 minutes on average. The bulky fatty tissue around the thymus made the orientation and the complete removal more difficult in a few patients. We experienced vascular injury in 4 cases and injury of the contralateral lung in 3 cases. Conversion was necessary in 2 cases (1 sternotomy and 1 thoracotomy), there were no nerve injuries. Assisted ventilation was necessary in case of ten patients in the postoperative period for a few hours; all other patients were extubated on the operating table. There was no need for repeated intubation and tracheostomy; there was no respiratory insufficiency and perioperative mortality. Duration of ICU care was 1.1 days on the average (0­11 days), that of the total hospital care 4.8 days on average (3­15 days). Duration of thoracic drainage was 1.16 days on average (1­4 days). Two patients (2.41%) died within one and five years after surgery. During 12­108 months (48 months on average) follow-up of 81 patients, 21 patients (25.3%) suffering from myasthenia total recovery was observed, pharmacologic remission was achieved in 4 patients (5.3%), minimal manifestation remained in 23 patients (24.1%), while in 28 patients (33.73%) other improvement was observed. The status of 4 patients (4.82%) remained unchanged and that of 4 patients (5.3%) worsened. Conclusion: VATS thymectomy represents a completely new surgical method for surgeons having experience in transsternal surgical technique. Bulky mediastinal fatty tissue makes surgery very difficult. The perioperative period is advantageous for the patients and also the long term follow-up results are acceptable. It is questionable that the thymus can be completely removed with this method in all cases.


Assuntos
Miastenia Gravis/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Timectomia/métodos , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
J Fungi (Basel) ; 6(3)2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32824977

RESUMO

Small, cysteine-rich and cationic antimicrobial proteins (AMPs) from filamentous ascomycetes promise treatment alternatives to licensed antifungal drugs. In this study, we characterized the Penicillium chrysogenum Q176 antifungal protein C (PAFC), which is phylogenetically distinct to the other two Penicillium antifungal proteins, PAF and PAFB, that are expressed by this biotechnologically important ascomycete. PAFC is secreted into the culture broth and is co-expressed with PAF and PAFB in the exudates of surface cultures. This observation is in line with the suggested role of AMPs in the adaptive response of the host to endogenous and/or environmental stimuli. The in silico structural model predicted five ß-strands stabilized by four intramolecular disulfide bonds in PAFC. The functional characterization of recombinant PAFC provided evidence for a promising new molecule in anti-Candida therapy. The thermotolerant PAFC killed planktonic cells and reduced the metabolic activity of sessile cells in pre-established biofilms of two Candidaalbicans strains, one of which was a fluconazole-resistant clinical isolate showing higher PAFC sensitivity than the fluconazole-sensitive strain. Candidacidal activity was linked to severe cell morphology changes, PAFC internalization, induction of intracellular reactive oxygen species and plasma membrane disintegration. The lack of hemolytic activity further corroborates the potential applicability of PAFC in clinical therapy.

18.
Int J Pharm ; 587: 119706, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32739390

RESUMO

In recent years, core-shell nanofibrous drug delivery systems have received increasing attention due to their ability to incorporate two or more active pharmaceutical ingredients (APIs) individually into the desired layer (either core or sheath) and thereby finely tune the release profiles of even incompatible drugs in one system. This study aims to perform formulation and solid-state characterisation of levofloxacin-loaded polylactic acid (PLA) - naproxen-sodium-loaded polyvinyl pyrrolidone (PVP) bicomponent core-shell fibrous sheets and examine the electro spinnability of the precursor combinations. The selected drugs have potential therapeutic relevance in similar systems intended for wound healing; however, in this study, they are used as model drugs to understand the physicochemical properties of a drug loaded system. In order to determine the best core- and shell-solution combination, a full factorial experimental design is used. A combination of various morphological (scanning electron microscopy and transmission electron microscopy) and microstructural characterisation techniques (X-ray photoelectron spectroscopy and Raman spectroscopy) was applied to non-invasively obtain information about the structure of the fibres and the embedded drugs. The results indicate that core-shell fibres of different compositions could be successfully prepared with various structural homogeneities. The best core-shell structure was obtained using a combination of 15% (w/w) shell concentration and 8% (w/w) PLA solution concentration. In addition to the conventional core-shell structural verification methods, the Raman spectroscopy method was implemented to reveal not only the core-shell structure of the PLA/PVP nanofibers but also the form of the embedded drugs. The Raman mapping of the fibres confirm the above results, and it is shown that an amorphous solid dispersion is formed as a result of the coaxial electrospinning process.


Assuntos
Portadores de Fármacos , Nanofibras , Liberação Controlada de Fármacos , Povidona
19.
Int J Pharm ; 586: 119593, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32622813

RESUMO

The effect of different frequencies and waveforms was investigated for the first time on alternating current electrospinning (ACES). PVPVA64, a polyvinylpyrrolidone-vinyl acetate copolymer was selected for the experiments as an important matrix for amorphous solid dispersions but never processed with ACES. It has been proved that ACES could be operated in a wide range of frequencies (40-250 Hz) and using different waveforms (sinusoidal, square, triangle, saw tooth) without significant changes in fiber morphology. Nevertheless, deterioration of the fiber formation process could be also observed especially at high frequencies. The developed PVPVA64-based fibers containing small amounts of additives (polyethylene oxide (PEO) and sodium dodecyl sulfate (SDS)) served as an excellent carrier for spironolactone (SPIR), a poorly soluble antihypertensive drug. As a result of the amorphously dispersed SPIR and the large surface area of the AC electrospun fibers immediate drug release could be achieved.


Assuntos
Eletricidade , Polietilenoglicóis , Liberação Controlada de Fármacos , Polímeros , Povidona , Solubilidade
20.
Int J Pharm ; 586: 119539, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32534161

RESUMO

In this study a new intravenous (i.v.) bolus dosage form of doxycycline was prepared by electrospinning. A tetracycline-type antibiotic with low water solubility (doxycycline (DOX)) was used with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as solubilizer. The new solid formulation could be produced with high (~80 g/h) productivity rate using high-speed electrospinning (HSES) from a water-based precursor solution. Freeze-dried DOX-HP-ß-CD was also prepared from the same precursor solution as HSES for comparison. Raman mapping showed that the amorphous DOX was uniformly distributed in the fibrous powder making precise dosing of the API possible. The new formulation's viability as an i.v. bolus product was examined with reconstitution test. The samples contained 100 mg of pure DOX (similarly to the products currently on the market). To ensure i.v. bolus applicability, the dissolution was carried out in 1.5 mL water. The final DOX concentration was 66.7 mg/(mL solvent), which is 7 times higher than the currently marketed formulation. The drug release was followed by UV-VIS spectrophotometry. The results confirmed that the reconstitution solution could be applied as an i.v. bolus dosage form. Moreover, the work confirmed that the continuous high-speed electrospinning process can be a viable high productivity alternative to freeze-drying.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Excipientes/química , Antibacterianos/química , Química Farmacêutica , Doxiciclina/química , Liberação Controlada de Fármacos , Liofilização , Pós , Solubilidade , Tecnologia Farmacêutica , Água/química
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