RESUMO
Levodopa administration as a gold standard in Parkinson's disease (PD) treatment is very valuable, however, long-term administration may cause some motor complications such as abnormal unintended movements and shortening response to each dose (wearing off phenomenon). Dopamine agonists were developed to reduce duration of immobile off periods and dependence to levodopa for improving motor impairments (Clarke et al., Cochrane Libr 1:1-23, 2000). Pramipexole is one of these nonergot dopamine agonists with high relative in vitro specificity and full intrinsic activity at D2 subfamily of dopamine receptors, with a higher binding affinity to D3 than to D4 or D2 receptor subtypes (Piercey, Clin Neuropharmacol 21:141-151, 1998). It can be advantageously administered as monotherapy or adjunctive therapy to levodopa to decrease side effects and increase effectiveness in both early and advanced PD treatment.
Assuntos
Antiparkinsonianos/uso terapêutico , Benzotiazóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Benzotiazóis/farmacocinética , Interações Medicamentosas , Humanos , Pramipexol , Resultado do TratamentoRESUMO
Among currently used cancer imaging methods, nuclear medicine modalities provide metabolic information, whereas modalities in radiology provide anatomical information. However, different modalities, having different acquisition times in separate machines, decrease the specificity and accuracy of images. To solve this problem, hybrid imaging modalities were developed as a new era, especially in the cancer imaging field. With widespread usage of hybrid imaging modalities, specific contrast agents are essentially needed to use in both modalities, such as single-photon emission computed tomography/computed tomography (SPECT/CT). Liposomes are one of the most desirable drug delivery systems, depending on their suitable properties. The aim of this study was to develop a liposomal contrast agent for the diagnosis and molecular imaging of tumor by SPECT/CT. Liposomes were prepared nanosized, coated with polyethylene glycol to obtain long blood circulation, and modified with monoclonal antibody 2C5 for specific tumor targeting. Although DTPA-PE and DTPA-PLL-NGPE (polychelating amphilic polymers; PAPs) were loaded onto liposomes for stable radiolabeling for SPECT imaging, iopromide was encapsulated into liposomes for CT imaging. Liposomes [(DPPC:PEG(2000)-PE:Chol:DTPA-PE), (PL 90G:PEG(2000)-PE:Chol:DTPA-PE), (DPPC:PEG(2000)-PE:Chol:PAPs), (PL 90G:PEG(2000)-PE:Chol:PAPs), (60:0.9:39:0.1% mol ratio)] were characterized in terms of entrapment efficiency, particle size, physical stability, and release kinetics. Additionally, in vitro cell-binding studies were carried out on two tumor cell lines (MCF-7 and EL 4) by counting radioactivity. Tumor-specific antibody-modified liposomes were found to be effective multimodal contrast agents by designating almost 3-8 fold more uptake than nonmodified ones in different tumor cell lines. These results could be considered as an important step in the development of tumor-targeted SPECT/CT contrast agents for cancer imaging.
Assuntos
Diagnóstico por Imagem , Lipossomos , Nanopartículas , Neoplasias/diagnóstico , Linhagem Celular Tumoral , Meios de Contraste , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipossomos/química , Imagem Multimodal , Neoplasias/patologia , Tamanho da Partícula , Polietilenoglicóis , Distribuição TecidualRESUMO
Molecular imaging is a relatively new discipline with a crucial role in diagnosis and treatment tracing of diseases through characterization and quantification of biological processes at cellular and sub-cellular levels of living organisms. These molecular targeted systems can be conjugated with contrast agents or radioligands to obtain specific molecular probes for the purpose of diagnosis of diseases more accurately by different imaging modalities. Nowadays, an interesting new approach to molecular imaging is the use of stealth nanosized drug delivery systems such as liposomes having convenient properties such as biodegradability, biocompatibility and non-toxicity and they can specifically be targeted to desired disease tissues by combining with specific targeting ligands and probes. The targeted liposomes as molecular probes in molecular imaging have been evaluated in this review. Therefore, the essential point is detection of molecular target of the disease which is different from normal conditions such as increase or decrease of a receptor, transporter, hormone, enzyme etc, or formation of a novel target. Transport of the diagnostic probe specifically to targeted cellular, sub-cellular or even to molecular entities can be performed by molecular imaging probes. This may lead to produce personalized medicine for imaging and/or therapy of diseases at earlier stages.
Assuntos
Sistemas de Liberação de Medicamentos , Imagem Molecular/métodos , Terapia de Alvo Molecular , Animais , Transporte Biológico , Meios de Contraste , Humanos , Ligantes , Lipossomos , Nanopartículas , Medicina de Precisão/métodos , Compostos RadiofarmacêuticosRESUMO
The interaction of radiation, whether it has natural or artificial, electromagnetic or particle-type characterizations, with materials causes different effects depending on the dose and type of radiation and physicochemical properties of the material. In the medical field, understanding the effect of radiation on a variety of materials including pharmaceuticals, medical devices, polymers as biomaterials, and packaging is crucial. Although there are many kinds of sterilization methods, the use of radiation in sterilization has many advantages such as being a substantially less toxic, safer terminal sterilization method. Radiosterilization is sterilization with an ionizing radiation such as gamma rays or electron beam (e-beam), the latter being a newer but less-frequently used technique. However, the need for large facilities with proper radiation protections for personnel and the environment from the effects of radiation and radioactive wastes makes this procedure highly costly. The effects of radiation on materials, especially pharmaceuticals and polymer-containing medical devices, cause degradation or chemical changes. The effects of radiation on a variety of different materials is a growing research area that can create safer techniques that reduce radiation damage and increase cost-effectiveness in the future. LAY ABSTRACT: Radiation can be used for positive purposes such as medical applications and the sterilization of pharmaceutical products, medical devices, and food and agricultural products as well as clinical applications such as diagnosis and/or therapy of a variety of diseases. The dose rate, time, type and emitted energy of the radiation are critical issues for determining its benefit/damage ratio. The sterilization of pharmaceuticals and medical devices that contain polymers can be achieved safely and effectively by irradiation. The sterilization of materials at the terminal phase-that is, in its final packaging materials-and its suitability to a variety of different kinds of packaging materials have brought additional value to radiosterilization. However, radiation sterilization is more expensive than the other sterilization methods that require large facilities. Although this method is safe in application, the effects of radiation on drugs and polymers must be evaluated by various analytical methods. In the nuclear chemistry and radiochemistry field, more effective and novel methods are being developed to decrease the harmful effects of radiation on materials.
Assuntos
Polímeros , Esterilização , Materiais Biocompatíveis/efeitos da radiação , Raios gama , Humanos , Polímeros/efeitos da radiação , Efeitos da Radiação , Radiação IonizanteRESUMO
Among different imaging modalities, Positron Emission Tomography (PET) gained importance in routine hospital practice depending on ability to diagnose diseases in early stages and tracing of therapy by obtaining metabolic information. The combination of PET with Computed Tomography (CT) forms hybrid imaging modality that gives chance to obtain better images having higher resolution by fusing both functional and anatomical images in the same imaging modality at the same time. Therefore, better contrast agents are essentially needed. The advance in research about developing drug delivery systems as specific nanosized targeted systems gained an additional importance for obtaining better diagnosis and therapy of different diseases. Liposomes appear to be more attractive drug delivery systems in delivering either drugs or imaging ligands to target tissue or organ of diseases with higher accumulation by producing in nano-scale, long circulating by stealth effect and specific targeting by modifying with specific ligands or markers. The combination of positron emitting radionuclides with liposomes are commonly in research level nowadays and there is no commercially available liposome formulation for PET imaging. However by conjugating positron emitter radionuclide with liposomes can form promising diagnostic agents for improved diagnosis and following up treatments by increasing image signal/contrast in the target tissue in lower concentrations by specific targeting as the most important advantage of liposomes. More accurate and earlier diagnosis of several diseases can be obtained even in molecular level with the use of stable and effectively radiolabeled molecular target specific nano sized liposomes with longer half-lived positron emitting radionuclides.