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1.
AAPS PharmSciTech ; 24(8): 225, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37945987

RESUMO

The physics of tablets mixtures has gained much attention lately. The purpose of this work is to evaluate the compaction properties of Kollidon® SR (KSR) in the presence of different excipients such as Microcrystalline cellulose (MCC), Monohydrous lactose (MH Lactose), Poly (vinyl acetate) (PVA100), and a water-soluble drug Diclofenac sodium (DNa) to prepare once daily formulation. Tablets were prepared using direct compression and were compressed into flat-faced tablets using hydraulic press at various pressures. The combination of MCC and KSR in the tablets showed reduced porosity, and almost constant low Py values as KSR levels increased; also, KSR-DNa tablets had higher percentage porosity and crushing strength values than KSR-MH Lactose tablets. The crushing strengths of KSR-MCC tablets were larger than those of KSR-DNa tablets. Ternary mixture tablets comprised of KSR-MCC-DNa showed decreased porosities and low Py values as the percentage of KSR increased especially at high compression pressures but had higher crushing strengths compared to KSR-DNa or MCC-DNa binary tablets. KSR-MH Lactose-DNa ternary tablets experienced lower porosities and crushing strengths compared to KSR-MCC-DNa tablets. Quaternary tablets of KSR-PVA100-MCC-DNa showed lower porosity and Py values than quaternary tablets obtained using similar proportion of MH Lactose instead of MCC. In conclusion, optimum quaternary tablets were obtained with optimum crushing strengths, relatively low Py, and moderate percentage porosities among all prepared quaternary tablets. The drug release of the optimum quaternary tablets demonstrated similar in vitro release profile compared to that of the marketed product with a mechanism of release that follows Korsmeyer-Peppas model.


Assuntos
Diclofenaco , Povidona , Preparações de Ação Retardada , Lactose/química , Comprimidos/química , DNA
3.
Pharm Dev Technol ; 28(1): 138-142, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36622883

RESUMO

In this study, a hardness tester was modified by attaching a metal blade to its testing area to obtain the minimum forces required to subdivide tablets along their diameters (F'). Moreover, the tensile strengths of subdividing tablets (TS') were calculated. Tablets of microcrystalline cellulose (MCC) weighing 0.5 g were produced at applied compression pressures of 21, 31, 41, 50, and 60 MPa. In addition, tablets of Ludipress®, and a 5:2 mixture of paracetamol to MCC weighing 0.7 g were produced at applied compression pressures of 77, 116, 154, 193, and 232 MPa. It was found that F' increased as the applied compression pressure used to produce the tablets increased until a maximum value was reached. This maximum value was at around 100 N for MCC and Ludipress® tablets and at around 76 N for paracetamol/MCC tablets. Moreover, a maximum value of TS' was reached at a porosity of 0.37 for MCC, 0.15 for Ludipress®, and 0.11 for paracetamol/MCC tablets. The maximum TS' values were at around 1.5 MPa for MCC and Ludipress® tablets and at around 0.9 MPa for paracetamol/MCC tablets. Therefore, both inter particulate bonding (tablet strength) and porosity (packing) affected the magnitudes of F' and TS'.


Assuntos
Acetaminofen , Acetaminofen/química , Porosidade , Dureza , Comprimidos/química , Resistência à Tração
4.
AAPS PharmSciTech ; 23(7): 262, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138243

RESUMO

Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.


Assuntos
Quitosana , Nanopartículas , Antipirina , Ácido Ascórbico , Portadores de Fármacos , Hidrodinâmica , Tamanho da Partícula , Polímeros , Propiltiouracila , Solubilidade , Teofilina
5.
Environ Mol Mutagen ; 62(5): 328-334, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34056770

RESUMO

For many years, organophosphate (OP) pesticides have been considered an attractive choice for pest control around the world. Excessive use of OPs is a concerning issue for human health. Although the genotoxic effect of these pesticides has been reported, studies that examined their aneuploidy-inducing effect are limited or absent. Therefore, we sought to investigate the potential of OP pesticides, which are extensively used in the Gaza Strip, to induce aneuploidy in human peripheral blood lymphocyte (PBL) cultures. To achieve this goal, we first assessed the cytotoxic effect of selected concentrations of Nemacur (fenamiphos), Rogor (dimethoate), and Dursban (chlorpyrifos) on human PBL cultures by the MTT assay. Then, fluorescence in situ hybridization (FISH) technique was used to determine the frequency of induced aneuploidy (chromosome loss or gain) in human PBL cultures treated with different concentrations of the three types of OPs. We found that all the OPs treatments used did not show appreciable cytotoxic effects. Increase in frequencies of aneuploidy, chromosome loss, and chromosome gain were observed after each treatment as compared to the results of their respective solvent control cultures, and that increase of aneuploidy was significantly evident at 0.050 mg/ml of Nemacur. It was also noticed that chromosome loss is more frequent than chromosome gain for each concentration of the three types of OPs. While the aneuploidy induction effect of the investigated OPs is not significant (except for the 0.050 mg/ml of Nemacur), these pesticides should be examined further since many people are exposed to them.


Assuntos
Aneuploidia , Clorpirifos/efeitos adversos , Aberrações Cromossômicas/induzido quimicamente , Dimetoato/efeitos adversos , Leucócitos Mononucleares/patologia , Linfócitos/patologia , Compostos Organofosforados/efeitos adversos , Inibidores da Colinesterase/efeitos adversos , Dano ao DNA , Humanos , Inseticidas/efeitos adversos , Leucócitos Mononucleares/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Praguicidas/efeitos adversos
6.
Clin Imaging ; 74: 131-138, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33493970

RESUMO

OBJECTIVE: Spigelian hernia is an uncommon congenital or acquired defect in the transversus abdominis aponeurosis with non-specific symptoms posing a diagnostic challenge. There is a paucity of radiology literature on imaging findings of Spigelian hernia. The objective of this study is to explore the role of MDCT in evaluating Spigelian hernia along with clinical and surgical implications. MATERIALS AND METHODS: In this IRB approved, HIPAA compliant retrospective observational analysis MDCT imaging findings of 43 Spigelian hernias were evaluated by two fellowship-trained radiologists. Imaging features evaluated were: presence of Spigelian hernia, laterality, relation to "hernia belt" (between 0 and 6 cm cranial to an imaginary axial line between both anterior superior iliac spines), the hernia neck and sac sizes, hernia content, and other coexistent hernias (umbilical, incisional, inguinal). Patient's demographics (age, gender, BMI, conditions with increased intra-abdominal pressure) were also recorded for any correlation. RESULTS: 60% (26/43) of Spigelian hernias were located below the hernia belt while 33% (14/43) within the hernia belt and 7% (3/43) above the hernia belt. The most common subtype of Spigelian hernia encountered was interparietal (84%). The mean hernia neck diameter was 3.4 cm, mean hernia sac volume was 329 cc. Hernia content included: fat (43/43) bowel (23/43), fluid (3/43). 3 patients had no clinical history provided, the remaining 37 patients' clinical presentation was asymptomatic in 73% (27/37), acute abdominal pain in 5% (2/37) and chronic abdominal pain in 22% (8/37). None of the hernia were incarcerated and none of the patients underwent emergent surgery. No significant correlation was noted between Spigelian hernia and causes of increased intra-abdominal pressure. 90% of our patients had other abdominal hernias. 30.9 was the mean BMI (20.8-69.1). CONCLUSION: Most of the Spigelian hernia occurred below the traditionally described hernia belt and the majority are of interparietal subtype that can be best diagnosed with MDCT in contrast to physical examination.


Assuntos
Hérnia Ventral , Músculos Abdominais , Dor Abdominal , Hérnia Ventral/diagnóstico por imagem , Hérnia Ventral/cirurgia , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Curr Drug Deliv ; 18(1): 54-64, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32735522

RESUMO

OBJECTIVE: The objective of this study was to evaluate the suitability of a ternary mixture of smart polymers comprised of Eudragit®E100, Eudragit®L100, and sodium alginate to serve as a carrier for sustained drug release for weakly basic drugs. The model drug chosen in this part of the study is Metronidazole. METHODS: Matrix tablet formulations were prepared by either direct compression or by wet granulation. Dissolution studies were conducted using USP XXΠ rotating paddle apparatus in three different consecutive stages (pH 1.2, 4.8, and 6.8). Tablets made of low to intermediate proportions of sodium alginate and approximately equal proportions of Eudragit®E100 and Eudragit®L100 were found to have a significant modification of drug release rates. RESULTS: Thus, indicating a potential for controlling the drug release for 12 hours depending on polymers ratios in the formulation. The ratio of sodium alginate to total Eudragit® polymers and the ratio of Eudragit®E100 to Eudragit®L100 within the ternary polymeric composition were found critical in determining the controlled release performance. CONCLUSION: Results of swelling studies were in agreement with the dissolution behaviors of the tablets. The findings suggest the significance of the ternary polymeric compositions in controlling the release of a weakly basic drug, Metronidazole.


Assuntos
Polímeros , Ácidos Polimetacrílicos , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Comprimidos
8.
Pharm. pract. (Granada, Internet) ; 18(2): 0-0, abr.-jun. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-194054

RESUMO

OBJECTIVE: To determine the accuracy, variability, and weight uniformity of tablet subdivision techniques utilized to divide the tablets of five drug products that are commonly prescribed for use as half tablets in Jordan. METHODS: Ten random tablets of five commonly subdivided drug products were weighed and subdivided using three subdivision techniques: hand breaking, kitchen knife, and tablet cutter. The five commonly subdivided drug products (warfarin 5 mg, levothyroxine 50 μg, levothyroxine 100 μg, candesartan 16 mg, and carvedilol 25 mg) were weighed. The weights were analyzed for acceptance, accuracy, and variability. Weight variation acceptance criteria were adopted in this work as a tool to indicate the properness of the subdivision techniques used to produce acceptable half tablets. Other relevant physical characteristics of the five products such as tablet shape, dimensions, face curvature, score depth, and crushing strength were measured. RESULTS: All tablets were round in shape, had weights that ranged between 100.63 mg (standard deviation=0.99) and 379.04 mg (standard deviation=3.00), and had crushing strengths that ranged between 23.29 N (standard deviation=3.58)and 103.35 N (standard deviation=14.98). Both candesartan and carvedilol were bi-convex in shape with an extent of face curvature equal to about 33%. In addition, percentage score depth of the tablets had a range between 0% and 24%. The accuracy and variability of subdivision varied according to the subdivision technique used and tablet characteristics. Accuracy range was between 81% and 109.8%. Moreover, the relative standard deviation was between 1.5% and 17.4%. Warfarin 5 mg subdivided tablets failed the weight variation test regardless of the subdivision technique used. Subdivision by hand produced half tablets that were acceptable for levothyroxine 50 μg and levothyroxine 100 μg. Subdivision by knife produced half tablets that were acceptable only for candesartan tablets. However, the tablet cutter produced half tablets that passed the weight variation test for four out of the five drug products tested in this study. CONCLUSIONS: The tablet cutter performed better than the other subdivision techniques used. It produced half tablets that passed the weight uniformity test for four drug products out of the five


No disponible


Assuntos
Humanos , Comprimidos/uso terapêutico , Autoadministração , Prescrições de Medicamentos , Reprodutibilidade dos Testes , Comprimidos/química , Tecnologia Farmacêutica/métodos , Erros de Medicação/prevenção & controle , Jordânia , Comprimidos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética
9.
Pharm Pract (Granada) ; 18(2): 1776, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377280

RESUMO

OBJECTIVE: To determine the accuracy, variability, and weight uniformity of tablet subdivision techniques utilized to divide the tablets of five drug products that are commonly prescribed for use as half tablets in Jordan. METHODS: Ten random tablets of five commonly subdivided drug products were weighed and subdivided using three subdivision techniques: hand breaking, kitchen knife, and tablet cutter. The five commonly subdivided drug products (warfarin 5 mg, levothyroxine 50 µg, levothyroxine 100 µg, candesartan 16 mg, and carvedilol 25 mg) were weighed. The weights were analyzed for acceptance, accuracy, and variability. Weight variation acceptance criteria were adopted in this work as a tool to indicate the properness of the subdivision techniques used to produce acceptable half tablets. Other relevant physical characteristics of the five products such as tablet shape, dimensions, face curvature, score depth, and crushing strength were measured. RESULTS: All tablets were round in shape, had weights that ranged between 100.63 mg (standard deviation=0.99) and 379.04 mg (standard deviation=3.00), and had crushing strengths that ranged between 23.29 N (standard deviation=3.58)and 103.35 N (standard deviation=14.98). Both candesartan and carvedilol were bi-convex in shape with an extent of face curvature equal to about 33%. In addition, percentage score depth of the tablets had a range between 0% and 24%. The accuracy and variability of subdivision varied according to the subdivision technique used and tablet characteristics. Accuracy range was between 81% and 109.8%. Moreover, the relative standard deviation was between 1.5% and 17.4%. Warfarin 5 mg subdivided tablets failed the weight variation test regardless of the subdivision technique used. Subdivision by hand produced half tablets that were acceptable for levothyroxine 50 µg and levothyroxine 100 µg. Subdivision by knife produced half tablets that were acceptable only for candesartan tablets. However, the tablet cutter produced half tablets that passed the weight variation test for four out of the five drug products tested in this study. CONCLUSIONS: The tablet cutter performed better than the other subdivision techniques used. It produced half tablets that passed the weight uniformity test for four drug products out of the five.

10.
Open Nurs J ; 12: 125-132, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30069269

RESUMO

BACKGROUND: This paper explores the opportunities and challenges for integrating patient safety education in undergraduate nursing curriculum. METHODS: Four dimensions of undergraduate nursing education are examined: National accreditation of nursing programs, building a competency-based nursing education, a model of nursing education and building faculty capacity in patient safety education and research. RESULTS: Incorporating patient safety in a nursing curriculum can be "institutionalized" by making it a pre-requisite for granting program accreditation. At the operational level, transforming undergraduate nursing education to incorporate inquiry-based learning and moving toward competency-based patient safety education are two key requirements for engaging the students with patient safety science. Building faculty capacity who are experts in both patient safety teaching and research remains a key challenge that needs to be addressed to enable a shift in the patient safety "mindset" for future nursing workforce. CONCLUSION: Efforts to introduce patient safety in nursing education are both necessary and timely, and should accommodate students' unique needs and cultural context.

11.
Clin Pharmacol ; 10: 63-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849468

RESUMO

OBJECTIVES: To evaluate the degree of anticoagulation achieved with different enoxaparin dosing regimens used in obese and morbidly obese patients in a hospital setting in Jordan. METHODS: All obese adult patients who were prescribed enoxaparin for various indications were invited to participate in the study. The anti-factor Xa (anti-Xa) level was checked once after 4-6 hours of the third or fourth dose of enoxaparin (at steady state). Patients were followed daily to evaluate drug efficacy and safety through their hospital course. RESULTS: Enoxaparin daily dose used for prophylaxis indications ranged from 0.3 to 0.85 mg/kg and from 0.31 to 2.25 mg/kg in case of certain treatment indications. Most participants who received enoxaparin for treatment indications (76.9%) were on capping dosing regimens, which was <1 mg/kg twice daily. On the other hand, most patients (88.5%) who received enoxaparin for prophylaxis indications were on a fixed 40 mg/d dose. Among the 52 patients who completed the study, 19 patients (36.5%) had therapeutic anti-Xa levels. The results showed no statistically significant associations between regimens that were used and achieving therapeutic anti-Xa level (p>0.05). No bleeding events or thrombocytopenia were noticed, and there was one case of recurrent thrombosis. CONCLUSION: Enoxaparin dosing regimens that were used for obese patients varied based on prescribing physicians. Regardless of the regimen used, the majority of participants had nontherapeutic anti-Xa. Individualized dosing regimens based on anti-Xa levels are warranted for obese patients on enoxaparin.

13.
Cancer Imaging ; 17(1): 9, 2017 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-28259177

RESUMO

Treatment options for hepatocellular carcinoma have evolved over recent years. Interventional radiologists and surgeons can offer curative treatments for early stage tumours, and locoregional therapies can be provided resulting in longer survival times. Early diagnosis with screening ultrasound is the key. CT and MRI are used to characterize lesions and determine the extent of tumour burden. Imaging techniques are discussed in this article as the correct imaging protocols are essential to optimise successful detection and characterisation. After treatment it is important to establish regular imaging follow up with CT or MRI as local residual disease can be easily treated, and recurrence elsewhere in the liver is common.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia
14.
Colloids Surf B Biointerfaces ; 144: 8-20, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27058278

RESUMO

Docetaxel (Dtxl) is currently the most common therapeutic option for prostate cancer (PC). However, adverse side effects and problems associated with chemo-resistance limit its therapeutic outcome in clinical settings. A targeted nanoparticle system to improve its delivery to and activity at the tumor site could be an attractive strategy for PC therapy. Therefore, the objective of this study was to develop and determine the anti-cancer efficacy of a novel docetaxel loaded, prostate specific membrane antigen (PSMA) targeted superparamagnetic iron oxide nanoparticle (SPION) (J591-SPION-Dtxl) formulation for PC therapy. Our results showed the SPION-Dtxl formulation exhibits an optimal particle size and zeta potential, which can efficiently be internalized in PC cells. SPION-Dtxl exhibited potent anti-cancer efficacy via induction of the expression of apoptosis associated proteins, downregulation of anti-apoptotic proteins, and inhibition of chemo-resistance associated protein in PC cell lines. J591-SPION-Dtxl exhibited a profound uptake in C4-2 (PSMA(+)) cells compared to PC-3 (PSMA(-)) cells. A similar targeting potential was observed in ex-vivo studies in C4-2 tumors but not in PC-3 tumors, suggesting its tumor specific targeting. Overall, this study suggests that a PSMA antibody functionalized SPION-Dtxl formulation can be highly useful for targeted PC therapy.


Assuntos
Dextranos/química , Nanopartículas de Magnetita/química , Terapia de Alvo Molecular , Nanopartículas/química , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Taxoides/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citosol/efeitos dos fármacos , Citosol/metabolismo , Docetaxel , Endocitose/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Taxoides/farmacologia , Tubulina (Proteína)/metabolismo
15.
Magn Reson Med ; 75(3): 1209-17, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25918870

RESUMO

PURPOSE: The purpose of the present study was to apply noninvasive methods for monitoring regeneration and mechanical properties of tissue-engineered cartilage in vivo at different growth stages using MR elastography (MRE). METHODS: Three types of scaffolds, including silk, collagen, and gelatin seeded by human mesenchymal stem cells, were implanted subcutaneously in mice and imaged at 9.4T where the shear stiffness and transverse MR relaxation time (T2 ) were measured for the regenerating constructs for 8 wk. An MRE phase contrast spin echo-based sequence was used for collecting MRE images. At the conclusion of the in vivo study, constructs were excised and transcript levels of cartilage-specific genes were quantitated using reverse-transcription polymerase chain reaction. RESULTS: Tissue-engineered constructs showed a cartilage-like construct with progressive tissue formation characterized by increase in shear stiffness and decrease in T2 that can be correlated with increased cartilage transcript levels including aggrecan, type II collagen, and cartilage oligomeric matrix protein after 8 wk of in vivo culture. CONCLUSION: Altogether, the outcome of this research demonstrates the feasibility of MRE and MRI for noninvasive monitoring of engineered cartilage construct's growth after implantation and provides noninvasive biomarkers for regeneration, which may be translated into treatment of tissue defects.


Assuntos
Materiais Biocompatíveis , Cartilagem Articular/fisiologia , Técnicas de Imagem por Elasticidade/métodos , Imageamento por Ressonância Magnética/métodos , Engenharia Tecidual/métodos , Animais , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Alicerces Teciduais
16.
J Acoust Soc Am ; 138(4): 2537-47, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26520336

RESUMO

Scattering from a cavity in a soft elastic medium, such as silicone rubber, resembles scattering from an underwater bubble in that low-frequency monopole resonance is obtainable in both cases. Arrays of cavities can therefore be used to reduce underwater sound transmission using thin layers and low void fractions. This article examines the role of cavity shape by microfabricating arrays of disk-shaped air cavities into single and multiple layers of polydimethylsiloxane. Comparison is made with the case of equivalent volume cylinders which approximate spheres. Measurements of ultrasonic underwater sound transmission are compared with finite element modeling predictions. The disks provide a deeper transmission minimum at a lower frequency owing to the drum-type breathing resonance. The resonance of a single disk cavity in an unbounded medium is also calculated and compared with a derived estimate of the natural frequency of the drum mode. Variation of transmission is determined as a function of disk tilt angle, lattice constant, and layer thickness. A modeled transmission loss of 18 dB can be obtained at a wavelength about 20 times the three-layer thickness, and thinner results (wavelength/thickness ∼ 240) are possible for the same loss with a single layer depending on allowable hydrostatic pressure.

17.
Biomaterials ; 46: 1-12, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25678111

RESUMO

Interaction of serum proteins and nanoparticles leads to a nanoparticle-protein complex formation that defines the rational strategy for a clinically relevant formulation for drug delivery, hyperthermia, and magnetic resonance imaging (MRI) applications in cancer nanomedicine. Given this perspective, we have examined the pattern of human serum protein corona formation with our recently engineered magnetic nanoparticles (MNPs). The alteration in particle size, zeta potential, hemotoxicity, cellular uptake/cancer cells targeting potential, and MRI properties of the MNPs after formation of human serum (HS) protein corona were studied. Our results indicated no significant change in particle size of our MNPs upon incubation with 0.5-50 wt/v% human serum, while zeta potential of MNPs turned negative due to human serum adsorption. When incubated with an increased serum and particle concentration, apolipoprotein E was adsorbed on the surface of MNPs apart from serum albumin and transferrin. However, there was no significant primary or secondary structural alterations observed in serum proteins through Fourier transform infrared spectroscopy, X-ray diffraction, and circular dichroism. Hemolysis assay suggests almost no hemolysis at the tested concentrations (up to 1 mg/mL) for MNPs compared to the sodium dodecyl sulfate (positive control). Additionally, improved internalization and uptake of MNPs by C4-2B and Panc-1 cancer cells were observed upon incubation with human serum (HS). After serum protein adsorption to the surface of MNPs, the close vicinity within T1 (∼1.33-1.73 s) and T2 (∼12.35-13.43 ms) relaxation times suggest our MNPs retained inherent MRI potential even after biomolecular protein adsorption. All these superior clinical parameters potentially enable clinical translation and use of this formulation for next generation nanomedicine for drug delivery, cancer-targeting, imaging and theranostic applications.


Assuntos
Proteínas Sanguíneas/química , Fenômenos Químicos , Nanopartículas de Magnetita/química , Adsorção , Animais , Materiais Biocompatíveis/farmacologia , Proteínas Sanguíneas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/toxicidade , Camundongos Nus , Tamanho da Partícula , Ligação Proteica/efeitos dos fármacos , Eletricidade Estática
18.
Tissue Eng Part C Methods ; 21(4): 347-55, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25190214

RESUMO

The tissue engineering community has been vocal regarding the need for noninvasive instruments to assess the development of tissue-engineered constructs. Medical imaging has helped fulfill this role. However, specimens allocated to a test tube for imaging cannot be tested for a prolonged period or returned to the incubator. Therefore, samples are essentially wasted due to potential contamination and transfer in a less than optimal growth environment. In turn, we present a standalone, miniature, magnetic resonance imaging-compatible incubator, termed the e-incubator. This incubator uses a microcontroller unit to automatically sense and regulate physiological conditions for tissue culture, thus allowing for concurrent tissue culture and evaluation. The e-incubator also offers an innovative scheme to study underlying mechanisms related to the structural and functional evolution of tissues. Importantly, it offers a key step toward enabling real-time testing of engineered tissues before human transplantation. For validation purposes, we cultured tissue-engineered bone constructs for 4 weeks to test the e-incubator. Importantly, this technology allows for visualizing the evolution of temporal and spatial morphogenesis. In turn, the e-incubator can filter deficient constructs, thereby increasing the success rate of implantation of tissue-engineered constructs, especially as construct design grows in levels of complexity to match the geometry and function of patients' unique needs.


Assuntos
Reatores Biológicos , Técnicas de Cultura de Células , Imageamento por Ressonância Magnética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Células Cultivadas , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos
19.
J Tissue Eng Regen Med ; 9(5): 481-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-23956239

RESUMO

Tissue engineering (TE) has been introduced for more than 25 years without a boom in clinical trials. More than 70 TE-related start-up companies spent more than $600 million/year, with only two FDA-approved tissue-engineered products. Given the modest performance in clinically approved organs, TE is a tenaciously promising field. The TE community is advocating the application of clinically driven methodologies in large animal models enabling clinical translation. This challenge is hindered by the scarcity of tissue biopsies and the absence of standardized evaluation tools, but can be negated through non-invasive assessment of growth and integration, with reduced sample size and low cost. Solving this issue will speed the transition to cost-efficient clinical studies. In this paper we: (a) introduce magnetic resonance elastography to the tissue-engineering and regenerative medicine (TERM) community; (b) review recent MRE applications in TERM; and (c) discuss future directions of MRE in TERM. We have used MRE to study engineered tissues both in vitro and in vivo, where the mechanical properties of mesenchymally derived constructs were progressively monitored before and after tissues were implanted in mouse models. This study represents a stepping stone toward the applications of MRE in directing clinical trials with low cost and likely expediting the translation to more relevantly large animal models and clinical trials.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Imageamento por Ressonância Magnética/métodos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Adipócitos/citologia , Animais , Biópsia , Cálcio/química , Gelatina/química , Glicerol/química , Humanos , Células-Tronco Mesenquimais/citologia , Mesoderma/patologia , Camundongos , Modelos Animais , Osteogênese , Resistência ao Cisalhamento , Estresse Mecânico
20.
J Vis Exp ; (88): e51654, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24998332

RESUMO

Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.


Assuntos
Doenças Autoimunes/patologia , Imageamento por Ressonância Magnética/métodos , Miocardite/patologia , Miocárdio/patologia , Animais , Doenças Autoimunes/fisiopatologia , Feminino , Coração/fisiopatologia , Camundongos , Camundongos Endogâmicos A , Miocardite/fisiopatologia
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