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1.
Artif Cells Nanomed Biotechnol ; 52(1): 35-45, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38112317

RESUMO

Fabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing. In the present work, sodium alginate/aloe vera/sericin (SA/AV/S) scaffold has been fabricated using a simple cost-effective casting method. The prepared SA/AV/S scaffolds were characterised for their physicochemical properties such as scanning electron microscope, UV-visible spectroscopy and Fourier transform infra-red spectroscopy. SA/AV/S scaffold showed good mechanical strength, swelling behaviour and antibacterial activity. In vitro experiments using erythrocytes proved the hemocompatible and biocompatible features of SA/AV/S scaffold. In vitro blood clotting assay performed using human blood demonstrated the haemostatic and blood absorption properties of SA/AV/S scaffold. Scratch wound assay was performed to study the wound healing efficacy of prepared scaffolds. Chick embryo chorioallantoic membrane assay carried out using fertilised embryos proved the angiogenic property of SA/AV/S scaffold. Thus, SA/AV/S scaffold could serve as a potential haemostatic healthcare product due to its outstanding haemostatic, antimicrobial, hemocompatible, biocompatible and angiogenic properties.


Assuntos
Aloe , Hemostáticos , Sericinas , Embrião de Galinha , Animais , Humanos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Alginatos/farmacologia , Alginatos/química , Aloe/química , Hemostáticos/farmacologia , Alicerces Teciduais/química , Antibacterianos/farmacologia , Antibacterianos/química , Hemostasia
2.
Magn Reson Med ; 91(1): 413-423, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37676121

RESUMO

PURPOSE: In this study, we compared two triarylmethyl (TAM) spin probes, Ox071 and Ox063 for their efficacy in measuring tissue oxygen levels under hypoxic and normoxic conditions by R2 *-based EPR oximetry. METHODS: The R2 * dependencies on the spin probe concentration and oxygen level were calibrated using deoxygenated 1, 2, 5, and 10 mM standard solutions and 2 mM solutions saturated at 0%, 2%, 5%, 10%, and 21% of oxygen. For the hypoxic model, in vivo imaging of a MIA PaCa-2 tumor implanted in the hind leg of a mouse was performed on successive days by R2 *-based EPR oximetry using either Ox071 or Ox063. For the normoxic model, renal imaging of healthy athymic mice was performed using both spin probes. The 3D images were reconstructed by single point imaging and multi-gradient technique was used to determine R2 * maps. RESULTS: The signal intensities of Ox071 were approximately three times greater than that of Ox063 in the entire partial pressure of oxygen (pO2 ) range investigated. The histograms of the tumor pO2 images were skewed for both spin probes, and Ox071 showed more frequency counts at pO2 > 32 mm Hg. In the normoxic kidney model, there was a clear delineation between the high pO2 cortex and the low pO2 medulla regions. The histogram of high-resolution kidney oximetry image using Ox071 was nearly symmetrical and frequency counts were seen up to 55 mm Hg, which were missed in Ox063 imaging. CONCLUSION: As an oximetric probe, Ox071 has clear advantages over Ox063 in terms of sensitivity and the pO2 dynamic range.


Assuntos
Neoplasias , Oximetria , Camundongos , Animais , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Oximetria/métodos , Oxigênio , Imageamento Tridimensional
3.
Metabolites ; 13(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36676994

RESUMO

Imaging tumor microenvironments such as hypoxia, oxygenation, redox status, and/or glycolytic metabolism in tissues/cells is useful for diagnostic and prognostic purposes. New imaging modalities are under development for imaging various aspects of tumor microenvironments. Electron Paramagnetic Resonance Imaging (EPRI) though similar to NMR/MRI is unique in its ability to provide quantitative images of pO2 in vivo. The short electron spin relaxation times have been posing formidable challenge to the technology development for clinical application. With the availability of the narrow line width trityl compounds, pulsed EPR imaging techniques were developed for pO2 imaging. EPRI visualizes the exogenously administered spin probes/contrast agents and hence lacks the complementary morphological information. Dynamic nuclear polarization (DNP), a phenomenon that transfers the high electron spin polarization to the surrounding nuclear spins (1H and 13C) opened new capabilities in molecular imaging. DNP of 13C nuclei is utilized in metabolic imaging of 13C-labeled compounds by imaging specific enzyme kinetics. In this article, imaging strategies mapping physiologic and metabolic aspects in vivo are reviewed within the framework of their application in cancer research, highlighting the potential and challenges of each of them.

4.
Environ Res ; 209: 112925, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35149110

RESUMO

Ischemic heart disease (IHD) is the major reason for death worldwide. Therapeutic angiogenesis serves as an effective approach to treat IHD. Sericin (S), a natural silk protein is widely used in regenerative medicine due to its excellent bioactive properties. Graphene oxide (GO) is extensively used in the field of biomedicine due to its amazing capacity to interact with biomolecules. The main objectives of the present study are to synthesize sericin functionalized graphene oxide (SGO) nanocomposites to treat diseases associated with deficient angiogenesis. Carbodiimide induced cross-linking strategy was employed to functionalize graphene oxide using sericin. The SGO nanocomposites had wrinkled flake like structure with good blood biocompatibility. In vivo chick embryo angiogenesis (CEA) assay was performed to prove the angiogenic potency of SGO nanocomposites. CEA assay results clearly indicated the development of new blood vessels in SGO treated chick embryos when compared with the control.


Assuntos
Grafite , Nanocompostos , Sericinas , Animais , Embrião de Galinha , Grafite/química , Nanocompostos/química , Sericinas/química , Sericinas/farmacologia
5.
Drug Chem Toxicol ; 45(2): 507-514, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32050810

RESUMO

Understanding the mechanism behind neuronal regeneration is critical for treating ischemic stroke and traumatic brain injury. The presence of neural stem cells in and around the sub-ventricular zone of human and also in zebrafish is evidenced. In this current study, the neuro-protective potential of nano-formulated hesperetin on injury-induced neurogenesis in zebrafish was assessed. Nanoformulation of hesperetin was prepared by anti-solvent precipitation technique using sodium dodecyl sulfate (SDS) as the stabilizing agent. The synthesized particles were characterized using SEM, DLS, XRD and FT-IR. Anti-oxidant capacity of nano hesperetin (nHST) in in vitro followed by in vivo studies in a traumatic brain injury (TBI) model of adult zebrafish (Danio rerio), catalase activity, histological analysis and gene expression studies for the genes Sox2, Nestin, Fabp7a and HuC were carried out. The synthesized particles were found to be in nanoscale and SDS had successfully integrated with hesperetin. Moreover, nHST had a significantly higher anti-oxidant capacity in vitro. Catalase levels in nHST treated group were significantly restored compared to other groups. Histological studies supported reduced tissue damage on oral administration of nano-hesperetin as compared to other groups. Gene expression studies showed that nano-hesperetin at a concentration of 10 µM when administered orally induced proliferation of neural stem cells without inducing cell death.


Assuntos
Lesões Encefálicas Traumáticas , Hesperidina , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Hesperidina/farmacologia , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Peixe-Zebra
6.
J Biomater Sci Polym Ed ; 31(1): 123-140, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31594474

RESUMO

India has an alarming rate of growth of cardiovascular diseases (CVD). Similar to cancer there is a significant role for epigenetic factors in the increasing prevalence of CVD. Targeting the epigenetic mechanism, viz., the DNA methylation processes, histone modifications, and RNA based arrangements is today considered as a potential therapeutic approach to CVD management. 5-Azacytidine is an epigenetic treatment drug that is involved in the demethylation of DNA. 5-Azacytidine is an FDA approved drug for myelodysplastic syndrome. However, the usage of 5-Azacytidine for CVD has not been found acceptable because of its poor stability in neutral solutions and shorter half-live which makes it toxic to the cells. A significant breakthrough in the use of 5-azacytidine for cell therapy and tissue engineering for CVD treatment has been gained based on its ability to differentiate mesenchymal stem cells into cardiomyocytes. This work addresses the further need for a sustained release of this drug, to reduce its toxicity to the stem cells. Electrospun PCL-gelatin fibres that are well aligned to provide a mat-like structure with sufficient porosity for differentiated cells to move forward have been synthesized. The crystalline character, porosity, fibre width, thermal behavior hydrophilicity of these scaffolds are in tune with those reported in the literature as ideal for cell proliferation and adhesion. FTIR measurements confirm the entrapment of 5-azacytidine on to the scaffold. The adsorption of the drug did not alter the characteristic features of the scaffold. Primary results on cell viability and cell morphology, as well as cardiomyocyte differentiation, have shown that PCL-gelatin scaffolds carrying 5-azacytidine developed in this work could serve as an ideal platform for mesenchymal stem cell differentiation into cardiomyocytes.


Assuntos
Azacitidina/química , Azacitidina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Gelatina/química , Miócitos Cardíacos/citologia , Nanoestruturas/química , Poliésteres/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Miócitos Cardíacos/efeitos dos fármacos
7.
Int J Biochem Cell Biol ; 114: 105566, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31283996

RESUMO

This work describes an effort to develop an antimicrobial agent (chlorogenic acid - CGA) loaded porous nanogel based on calcium phosphate-chitosan (CaPNP@Chi) nanogel with biofilm degradative properties and has potential applications in restorative dentistry. The nanogel was prepared by ionic gelation of calcium phosphate nanoparticles and chitosan in the ratio of 1.25: 1. Chlorogenic acid was loaded to the nanoparticles as an ethanolic solution and the encapsulation efficiency determined by chromatographic techniques. The particle size and morphology of CaPNP@Chi and CaPNP@Chi@CGA was determined by dynamic light scattering and scanning electron microscopic techniques. The minimum inhibitory concentration against S. aureus and K. pneumoniae was determined through the well diffusion method. The biofilm formation and biofilm decay were studied through staining assays. The toxicity, if any of the nanogel was assessed by MTT assay against HaCaT cells. All data were statistically analyzed. The composite had a CGA encapsulation efficiency of 70% and was thermally stable up to 124 °C. The zone of inhibition was found to be 18.7 mm ± 0.6 against S. aureus. CaPNP@Chi@CGA showed a 68% increase in biofilm degradation when compared with the untreated group. Results obtained in this study suggest that the positively charged nanogel interacted with the bacterial cell membrane and brought about the disruption of the cell membrane. Also, CaPNP@Chi@CGA was observed to be nontoxic up to 40 µg/mL to HaCaT cells. These results support the potential of CaPNP@Chi@CGA nanogel for biofilm degradation and its application as filling material in restorative dentistry.


Assuntos
Materiais Biocompatíveis , Biofilmes/efeitos dos fármacos , Fosfatos de Cálcio , Ácido Clorogênico , Klebsiella pneumoniae/fisiologia , Nanogéis/química , Staphylococcus aureus/fisiologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Biofilmes/crescimento & desenvolvimento , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Ácido Clorogênico/química , Ácido Clorogênico/farmacologia
8.
Drug Chem Toxicol ; 42(1): 84-93, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30103634

RESUMO

In recent years, nanoparticles are being used extensively in personal healthcare products such as cosmetics, sunscreens, soaps, and shampoos. Particularly, metal oxide nanoparticles are gaining competence as key industrial constituents, progressing toward a remarkable rise in their applications. Zinc oxide and titanium oxide nanoparticles are the most commonly employed metal oxide nanoparticles in sunscreens, ointments, foot care, and over the counter topical products. Dermal exposure to these metal oxides predominantly occurs through explicit use of cosmetic products and airway exposure to nanoparticle dusts is primarily mediated via occupational exposure. There is a compelling need to understand the toxicity effects of nanoparticles which can easily enter the cells and induce oxidative stress. Consequently, these products have become a direct source of pollution in the environment and thereby greatly impact our ecosystem. A complete understanding of the toxicity mechanism of nano-ZnO is intended to resolve whether and to what extent such nanoparticles may pose a threat to the environment and to human beings. In this review article, we have discussed the characteristics of metal oxide nanoparticles and its applications in the cosmetic industry. We have also highlighted about their toxicity effects and their impact on human health.


Assuntos
Cosméticos/química , Nanopartículas/toxicidade , Óxido de Zinco/toxicidade , Animais , Linhagem Celular , Cosméticos/normas , Relação Dose-Resposta a Droga , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Propriedades de Superfície , Testes de Toxicidade , Óxido de Zinco/química , Óxido de Zinco/farmacocinética
9.
Int J Hematol Oncol Stem Cell Res ; 12(2): 153-165, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30233778

RESUMO

Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

10.
IET Nanobiotechnol ; 12(6): 727-732, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30104445

RESUMO

Research dealing with early diagnosis and efficient treatment in colon cancer to improve patient's survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non-specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated form (CL-SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti-cancer activity against colon cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Lipossomos/farmacologia , Lycopodium/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Apoptose/efeitos dos fármacos , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipossomos/síntese química , Lipossomos/química , Nanocompostos/química , Células Tumorais Cultivadas
11.
Oncotarget ; 9(7): 7739-7748, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29484148

RESUMO

Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS. Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS, validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

12.
Curr Drug Deliv ; 15(5): 652-657, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28847271

RESUMO

BACKGROUND: Biopolymeric nanoparticles comprising chitosan-alginate have attracted interest in drug delivery due to their protective nature, biocompatibility, biodegradability and hydrophilicity. OBJECTIVE: The present study was designed to encapsulate levofloxacin in chitosan-alginate hybrid gel for controlled release and to evaluate the effect of divalent alkaline earth metal ions (Mg2+, Ca2+, Sr2+, Ba2+) on encapsulation efficiency and drug release kinetics considering their role in polyelectrolyte gelation method. METHOD: Divalent metal ions control the rigidity and elasticity of the hydrogels and have the ability to change the shape and size of nanostructure formed by chitosan-alginate. The particle size increases and encapsulation efficiency decreases with the size of the divalent ions. Spherical shaped particles were formed by Mg2+ and Ca2+, whereas Sr2+ and Ba2+ produced non-spherical particles. RESULTS: SEM image clearly shows transformation of sphere to truncated tetrahedron by Sr2+ and clear rod shape by Ba2+. CONCLUSION: Therefore, it is concluded that metal ions have significant influence on the morphology and drug encapsulation and release profile of the chitosan-alginate hybrid polymer nanoparticles.


Assuntos
Alginatos/química , Cátions Bivalentes/química , Quitosana/química , Metais/química , Nanopartículas/química , Polímeros/química , Antibacterianos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Levofloxacino/química , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura
13.
Int J Hematol Oncol Stem Cell Res ; 12(3): 230-234, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30595826

RESUMO

In recent years, mesenchymal stem cells have provoked much attentiveness in the field of regenerative medicine because of their differentiation potential and the capability to facilitate tissue repair via the emancipation of biologically active molecules. They have gained interest because of their distinctive curative properties. Mesenchymal stem cells are isolated from the Wharton's jelly part of umbilical cord possessing higher proliferation capacity, immunomodulatory activity, plasticity, as well as self-renewal capacity than the mesenchymal stem cells from various origins, and it is considered to be the best resource for allogeneic transplantation. The isolated umbilical cord-derived mesenchymal stem cells are cultured in the Dulbecco's Modified Eagle's Medium, and thereby it begins to release soluble factors into the medium during the period of culture which is termed as conditioned medium. This conditioned media has both differentiation capacity and therapeutic functions. Thus, it can be able to differentiate the cells into different lineages and the paracrine effect of these cells helps in replacement of the damaged cells. This medium may accord to optimization of diagnostic and prognostic systems as well as the generation of novel and targeted therapeutic perspectives.

14.
Drug Discov Today ; 22(8): 1224-1232, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28545838

RESUMO

Despite advances in treatment modalities, colon cancer (CC) is the third most common cause of cancer-related death worldwide. Subsequent unfavorable effects owing to toxicity of conventional drugs are a challenging problem associated with chemotherapy. There is noticeable concern toward site-specific/targeted delivery of chemotherapeutic drugs specifically to the affected site of the colon in a predictable and reproducible manner. However, the biggest challenge in successful drug targeting for the colon is avoidance of drug absorption and/or degradation in the upper gastrointestinal tract before the drug reaches the colon. Nanoparticles endowed with targeting abilities offer a novel approach for site-specific delivery of chemotherapeutic agents. The present review focuses on recent approaches for colon-specific drug delivery (CDDS) and aims to unveil the emerging possibilities and advances in the treatment of CC with CDDS.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Colo/metabolismo , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/metabolismo , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/uso terapêutico
15.
Mater Sci Eng C Mater Biol Appl ; 70(Pt 1): 728-735, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27770948

RESUMO

A transition of amyloidogenic protein by alternative folding pathway under certain conditions leads to the formation of protease resistant amyloid fibrils, having predominantly cross ß structure. These amyloids are related to various neurodegenerative diseases and clearance of such amyloids may be a therapeutic approach for amyloid-related diseases. Insulin, that can form amyloids, is widely used as a model amyloidogenic protein for the study of various amyloid related diseases. In this study, insulin amyloids were formed in vitro and the potential of Serratiopeptidase (SP), a fibrinolytic-like serine protease, towards the dissociation of insulin amyloids was explored. The dissociation of the amyloids was demonstrated using in vitro and in vivo using zebrafish model. The amyloid dissociation property was compared with a standard amyloid dissociating enzyme nattokinase (NK). SP shows better amyloid dissociation ability than NK and therefore, SP can be considered as amyloid dissociating agent with potential as a drug candidate for different amyloid related disorders.


Assuntos
Amiloide/metabolismo , Insulina/metabolismo , Peptídeo Hidrolases/metabolismo , Animais , Dicroísmo Circular , Difusão Dinâmica da Luz , Fibrinólise , Humanos , Microscopia de Força Atômica , Tamanho da Partícula , Peixe-Zebra
16.
J Biomed Mater Res B Appl Biomater ; 104(4): 817-24, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26460478

RESUMO

Magnetic resonance imaging has acquired importance as a major tool for diagnosis and staging of cancers in humans. Injection of certain imaging agents have proved to improve contrast between normal and cancer cells on magnetic resonance imaging (MRI). Using the principles of MR contrast imaging, we have designed a dual mode (T1 and T2) contrast agent based on folic acid functionalized manganese ferrite nanoparticles (MNP) entrapped in 3G polyamidoamide (PAMAM) dendrimers. The ratio of Mn:Fe was tuned to achieve optimal performance. This multifunctional nanocarrier system was developed for targeting cancer cells to produce both T1 and T2 contrast which in turn helps in better diagnosis and staging of cancer. FTIR spectroscopy, X-Ray diffraction, atomic absorption spectroscopy, UV-Visible spectroscopy, and dynamic light scattering measurements were employed to characterize the multifunctional system at different stages of engineering. The ratio of relaxivities r2/r1 is 4.6 at 1.5 T for the MNP prepared with 0.5 molar ratio of Mn/Fe based on MR images obtained from phantom and tumor bearing mouse. The value of r2/r1 shows that the 0.5 molar ratio of Mn/Fe can be used to prepare MNP for the production of dual mode contrast in MR imaging.


Assuntos
Meios de Contraste , Dendrímeros , Compostos Férricos , Imageamento por Ressonância Magnética/métodos , Manganês , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Animais , Meios de Contraste/química , Meios de Contraste/farmacologia , Dendrímeros/química , Dendrímeros/farmacologia , Feminino , Compostos Férricos/química , Compostos Férricos/farmacologia , Manganês/química , Manganês/farmacologia , Camundongos
17.
Mater Sci Eng C Mater Biol Appl ; 56: 501-10, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26249620

RESUMO

Zinc oxide (ZnO) is explicitly used in sunscreens and cosmetic products; however, its effect in vivo is toxic in some cases. The UV blocking efficacy of ZnO nanoparticles is lost due to photocatalysis. To isolate a lower toxic species of sunblockers, ZnO nanoparticles were synthesized and coated with chitosan - a natural polymer (ZnO-CTS) and polyethylene glycol (PEG) - a synthetic polymer (ZnO-PEG). Coating with CTS and PEG circumvented the photocatalytic activity, increased the stability and improved the UV absorption efficacy. The effect of ZnO, ZnO-CTS and ZnO-PEG nanoparticles in vivo on zebrafish embryo revealed lower deposition of ZnO-CTS and ZnO-PEG nanoparticles atop the eggs compared to ZnO. The survival of zebrafish embryos was always found to be higher in case of ZnO-CTS with respect to ZnO-treated ones. PEG coating exhibited better UV attenuation, but, in vivo it induced delayed hatching. Thus, one of the reasons for better survival could be attributed to lower aggregation of ZnO-CTS nanoparticles atop eggs thereby facilitating the breathing of embryos.


Assuntos
Materiais Revestidos Biocompatíveis , Teste de Materiais , Nanopartículas/química , Protetores Solares , Óxido de Zinco , Animais , Quitosana/química , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Protetores Solares/química , Protetores Solares/farmacologia , Raios Ultravioleta , Peixe-Zebra , Óxido de Zinco/farmacologia
18.
J Biomed Nanotechnol ; 9(2): 177-92, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23627044

RESUMO

The present study focused on the development of a novel biodegradable nanoparticle system based on polyethyleneglycol-modified gelatin (PEG-GEL) and polylactic acid (PLA) biopolymers for improving the photodynamic efficacy of cyclohexane-1,2-diamino hypocrellin B (CHA2HB), a potent photodynamic therapeutic (PDT) agent. The CHA2HB-loaded PEG-GEL/PLA nanoparticles showed near-spherical morphology with an average size of 190 nm at a PLA to PEG-GEL ratio of 1:3. The drug loading was sufficient enough to produce potentially toxic reactive oxygen species (ROS) needed for photodynamic therapy (PDT). Slow and controlled drug release was observed in normal conditions, whereas enzyme assistance resulted in a relatively fast release due to partial disintegration of CHA2HB-loaded PEG-GEL/PLA nanoparticles. In vitro experiments indicated that CHA2HB-loaded PEG-GEL-PLA nanoparticles are efficiently taken up by cancer cells such as human breast adenocarcinoma (MCF-7), human gastric sarcoma (AGS) and mice specific Dalton's lymphoma (DLA) in a time dependent manner. Further, CHA2HB-loaded PEG-GEL/PLA nanoparticles evoked superior phototoxicity compared to free-CHA2HB towards all the three cell lines investigated. Interestingly, PDT effectiveness was different for the different cell type studied. CHA2HB-loaded PEG-GEL/PLA nanoparticles induced both apoptotic and necrotic cell death as a result of photoirradiation. Thus, our data suggest that PEG-GEL/PLA nanoparticles are highly effective in delivery and phototoxic enhancement of CHA2HB against model cancer cells in vitro.


Assuntos
Gelatina/química , Ácido Láctico/química , Nanopartículas/química , Perileno/análogos & derivados , Fotoquimioterapia , Polietilenoglicóis/química , Polímeros/química , Quinonas/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Microscopia de Força Atômica , Microscopia de Fluorescência , Nanopartículas/ultraestrutura , Tamanho da Partícula , Perileno/farmacologia , Perileno/toxicidade , Fotodegradação , Fármacos Fotossensibilizantes/farmacologia , Poliésteres , Quinonas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Resultado do Tratamento
19.
J Biomed Nanotechnol ; 8(1): 43-56, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22515093

RESUMO

Nanoparticles formulated from biodegradable and natural polymer gelatin, were investigated for their potential to enable efficient delivery and enhanced efficacy of a well-known photodynamic agent, Hypocrellin B (HB). The HB-loaded poly(ethylene glycol) modified gelatin nanoparticles (HB-PEG-GNP) possessed near-spherical shape, with particle size in the range of 292 +/- 42 nm, and demonstrated characteristic optical properties for photodynamic therapy (PDT). Photophysical studies of the HB-PEG-GNP demonstrated photogeneration of reactive oxygen species (ROS). The nanoparticles were tested for cellular uptake in vitro, on Daltons' Lymphoma Ascites (DLA) cells and demonstrated dose dependent phototoxicity upon visible light treatment. HB-PEG-GNP induced mitochondrial damage, as investigated by JC-1 staining, leading to apoptotic cell death. Biodistribution measurements revealed that nanoformulation reduces liver uptake of HB-PEG-GNP and increases tumour uptake with time. In vivo PDT studies in solid tumour bearing mice showed markedly significant regression (38.5 +/- 2.2%, p < 0.05) for HB-PEG-GNP treated mice in contrast to those treated with free HB (29.36 +/- 1.62%). The present study reveals gelatin nanocarrier to be an effective drug delivery system for enhancement of therapeutic efficacy of the PDT agent, HB.


Assuntos
Portadores de Fármacos/química , Gelatina/química , Linfoma/tratamento farmacológico , Nanopartículas/química , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Quinonas/administração & dosagem , Quinonas/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/farmacocinética , Linfoma/metabolismo , Linfoma/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Microscopia de Fluorescência , Tamanho da Partícula , Perileno/administração & dosagem , Perileno/química , Perileno/farmacocinética , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Quinonas/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Cancer Nanotechnol ; 2(1-6): 95-103, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-26069488

RESUMO

Photodynamic therapy (PDT) is a promising treatment methodology whereby diseased cells and tissues are destroyed by reactive oxygen species (ROS) by using a combination of light and photosensitizers (PS). The medical application of Rose Bengal (RB), photosensitizer with very good ROS generation capability, is limited due to its intrinsic toxicity and insufficient lipophilicity. In this report, we evaluate the potential of polyamidoamine (PAMAM) dendrimers in delivering RB and its phototoxic efficiency towards a model cancer cell line. The spherical, nanoscaled dendrimers could efficiently encapsulate RB and showed characteristic spectral responses. The controlled release property of dendrimer-RB formulation was clearly evident from the in vitro drug release study. ROS generation was confirmed in dendrimer-RB system upon white light illumination. Photosensitization of Dalton's Lymphoma Ascite (DLA) cells incubated with dendrimer-RB formulation caused remarkable photocytotoxicity. Importantly, the use of dendrimer-based delivery system reduced the dark toxicity of RB.

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