RESUMO
Understanding the effect of liposome size on tendency for accumulation in tumour tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is difficult, and differences in compositions itself modify distribution behaviour. Here, a commercial microfluidic format as well as traditional methods was used to prepare doxorubicin-loaded liposomes of different size distributions but with the same lipid composition, and drug retention, biodistribution and localization in tumour tissues were evaluated. The small (â¼50 nm diameter) liposomes prepared by microfluidics and large (â¼75 nm diameter) liposomes displayed similar drug retention in in vitro release studies, and similar biodistribution patterns in tumour-bearing mice. However, the extent of extravasation was clearly dependent on size of the liposomes, with the small liposomes showing tissue distribution beyond the vascular area compared to the large liposomes. The use of microfluidics to prepare smaller size distribution liposomes compared to sonication methods is demonstrated, and allowed preparation of different size distribution drug carriers from the same lipid composition to enable new understanding of tissue distribution in compositionally consistent materials is demonstrated.
Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos , Lipossomos , Microfluídica , Animais , Transporte Biológico , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Tamanho da Partícula , Polietilenoglicóis/administração & dosagemRESUMO
Polymerization-induced self-assembly (PISA) is a facile one-pot synthetic technique for preparing polymeric nanoparticles with different sizes and shapes for application in a variety of fields including nanomedicine. However, the in vivo biodistribution of nanoparticles obtained by PISA still remains unclear. To address this knowledge gap, we report the synthesis, cytotoxicity, and biodistribution in an in vivo tumor-bearing mouse model of polystyrene micelles with various sizes and polystyrene filomicelles with different lengths prepared by PISA. First, a library of nanoparticles was prepared comprised of poly(glycidyl methacrylate)-b-poly(oligo(ethylene glycol) methyl ether methacrylate)-b-polystyrene polymers, and their size and morphology were tuned by varying the polystyrene block length without affecting the surface chemistry. The 3H) ethanolamine, and a biodistribution study was carried out in nude mice bearing HT1080 tumor xenografts 48 h after intravenous delivery. In this model, we found that small spherical polystyrene core nanoparticles with a PEG corona (diameter 21 nm) have the highest tumor accumulation when compared to the larger spherical nanoparticles (diameter 33 nm) or rodlike (diameter 37 nm, contour length 350-500 nm) or wormlike counterparts (diameter 45 nm, contour length 1-2 µm). This finding has provided critical information on the biodistribution of polystyrene core nanoparticles with a PEG corona of different sizes and shapes prepared by the PISA technique and will inform their use in medical applications.
Assuntos
Nanopartículas/química , Nanopartículas/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Micelas , Nanomedicina/métodos , Tamanho da Partícula , Polietilenoglicóis/química , Polimerização , Polímeros/química , Poliestirenos/química , Distribuição TecidualRESUMO
Hydrogels have emerged as a versatile class of polymeric materials with a wide range of applications in biomedical sciences. The judicious choice of hydrogel precursors allows one to introduce the necessary attributes to these materials that dictate their performance towards intended applications. Traditionally, hydrogels were fabricated using either polymerization of monomers or through crosslinking of polymers. In recent years, dendrimers and dendrons have been employed as well-defined building blocks in these materials. The multivalent and multifunctional nature of dendritic constructs offers advantages in either formulation or the physical and chemical properties of the obtained hydrogels. This review highlights various approaches utilized for the fabrication of hydrogels using well-defined dendrimers, dendrons and their polymeric conjugates. Examples from recent literature are chosen to illustrate the wide variety of hydrogels that have been designed using dendrimer- and dendron-based building blocks for applications, such as sensing, drug delivery and tissue engineering.
Assuntos
Dendrímeros/química , Hidrogéis/síntese química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Química Click , Hidrogéis/química , Estrutura Molecular , Engenharia TecidualRESUMO
Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85-90 % of all lymphomas. Clinical treatment of NHL is based on the "4-drug regimen" known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity.
Assuntos
Sobrevivência Celular , Ciclodextrinas , Liberação Controlada de Fármacos , Linfoma não Hodgkin , Nanopartículas , Rituximab , Linfoma não Hodgkin/tratamento farmacológico , Humanos , Rituximab/administração & dosagem , Rituximab/química , Nanopartículas/química , Linhagem Celular Tumoral , Ciclodextrinas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/química , Vincristina/administração & dosagem , Vincristina/farmacologia , Vincristina/química , Prednisona/administração & dosagem , Prednisona/química , Prednisona/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/química , Ciclofosfamida/administração & dosagem , Ciclofosfamida/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Portadores de Fármacos/química , Tamanho da Partícula , CeluloseRESUMO
Background Local antibiotic applications have been used in chronic osteomyelitis and have been defined as an adjunctive treatment method. Biodegradable materials are also used for the same purpose by adding antibiotics. The fact that it does not require additional surgery to be removed is an important advantage. In this study, we intended to develop a new biodegradable drug-loaded polymeric scaffold with good antibiotic release and compare the microbiological results with antibiotic-impregnated bone cement. Methodology A tissue scaffold containing poly(2-hydroxyethyl methacrylate) (PHEMA) was prepared in our laboratory and loaded with ertapenem and daptomycin antibiotics. The surface morphology and pore geometries of drug-loaded and unloaded scaffolds were analyzed by a scanning electron microscope under vacuum. The dose-dependent antiproliferative effects of PHEMA scaffold, drug-loaded scaffold, cement, and drug-loaded cement on osteoblast cells were investigated. To evaluate drug release kinetics, the absorbance values of the scaffold loaded with ertapenem and daptomycin were measured with the spectrometer. For microbiological tests, ertapenem and daptomycin-impregnated cement and scaffold, as well as the control scaffold and cement samples, were investigated for their antibacterial activities on Staphylococcus aureus and Klebsiella pneumoniae strains using the disc diffusion method. These microorganisms are one of the most common microorganisms in osteomyelitis. Results The efficacy of antibiotic-impregnated scaffold and cement on both gram-negative and gram-positive microorganisms was investigated. The daptomycin zone diameter in S. aureus ATCC 29233 strain was 17 mm, whereas it was 24 mm for scaffold and 22 mm for cement. Scaffold was found to be more effective than cement against S. aureus strain. The K. pneumoniae ATCC BAA-2814 strain was found to be resistant to ertapenem, but the zone diameter was 21 mm for scaffold and 20 mm for cement. Ertapenem-loaded scaffold was found to be more effective than cement. It was found that the antimicrobial activity of the scaffold was higher than cement. When we evaluated the release profiles, for the daptomycin-loaded cement group, 98% of daptomycin was cumulatively released within 30 minutes, and for the daptomycin-loaded scaffold group, 100% of daptomycin was cumulatively released in six days. To compare ertapenem-loaded cement and scaffold, 98% of ertapenem was cumulatively released within 10 minutes in the cement group. For the scaffold group, 100% of ertapenem was cumulatively released in 17 days. We found that the scaffold released the antibiotic more slowly and for a longer duration. Therefore, it was thought that the scaffold would be more effective on biofilm and the treatment of osteomyelitis would be more successful. Conclusions The produced scaffold was compared with cement, and it was concluded that the scaffold had better release and antimicrobial efficacy. Scaffold is more advantageous than cement because it is bioeliminable. Thus, there is no need for a second surgical intervention with the likely prevention of mortality and morbidity. Because of all these features, the scaffold seems promising in the local treatment of osteomyelitis.
RESUMO
Plants with antidiabetic activities provide important sources for the development of new drugs in the treatment of diabetes mellitus. In the present study, we investigated possible antihyperglycemic and antioxidative activities of the aerial part of the Matricaria chamomilla L. ethanolic extract (MCE) in streptozotocin (STZ; 70 mg/kg, i.p.)-induced diabetic rats. The following groups were assigned; sham (did not receive any substance), STZ + distilled water (control), STZ + 5 mg/kg glibenclamide, STZ + 20 mg/kg MCE, STZ + 50 mg/kg MCE, STZ + 100 mg/kg MCE. Diabetic rats were treated for 14 days by gavage. Postprandial blood glucose levels, malondialdehyde, reduced glutathione (GSH), nitrate, nitrite, ascorbic acid, retinol, beta-carotene, superoxide dismutase, and catalase levels were measured, and immunohistochemical studies were performed in all of the groups. The obtained data showed that STZ resulted in oxidative stress and affected the antioxidant status. Treatment with different doses of MCE significantly reduced postprandial hyperglycemia and oxidative stress, and augmented the antioxidant system. In histological investigations, MCE treatment protected the majority of the pancreatic islet cells, with respect to the control group. As a result, MCE exhibited significant antihyperglycemic effect and protected beta-cells in STZ-diabetic rats, in a dose-dependent manner, and diminished the hyperglycemia-related oxidative stress.