RESUMO
The world population is ageing at an alarming rate, currently increasing at around 3% per year for people over 60 years. This fast growing demography is largely unproductive and prone to many brain disorders such as Alzheimer's disease, Parkinson's disease, and brain tumors. Currently available treatment modalities are inadequate to stop neural degeneration or to completely eradicate cancer cells. Exogenously engineered scaffolds hold great potential for in vivo brain regeneration and functional restoration. Ideally, scaffolds for brain tissue engineering should be biocompatible, non-toxic, and electroactive with the ability to encourage neural elongation. These scaffolds have been successfully fabricated from a wide range of materials and techniques. Different types of stem cells have also been investigated for their ability to differentiate to nerve or glial tissue. The success of tissue engineering can thus be envisioned as a panacea for "retooling" of both individual's ability and for immense long-term benefit of society.
Assuntos
Encefalopatias/terapia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais , Envelhecimento , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Encéfalo/citologia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Encefalopatias/fisiopatologia , Humanos , Regeneração , Alicerces Teciduais/químicaRESUMO
MUC1 aptamer-functionalized PLA-PEG nanocarriers at various w/w ratios (polymer to doxorubicin weight ratio) were prepared by a double emulsion method. Physiochemical properties, encapsulation efficiency (EE), loading content (LC) and in vitro release kinetics of DOX were assessed. Furthermore, cytotoxicity and antitumor activity of prepared PLA-PEG-Apt/DOX NPs at w/w ratio 10:1 were evaluated by MTT assay and flow cytometry against MUC1-overexpressing A-549 cell line. Targeted nanocarriers (PLA-PEG-Apt/DOX NPs at w/w ratio 10:1) induced higher apoptosis rate (36.3 ± 3.44%) for 24 h in MUC1 positive A-549 cancer cells in compare to non-targeted form (PLA-PEG/DOX NPs at w/w ratio 10:1, 11.37 ± 1.65%) and free DOX (4.35 ± 0.81%). In other word, the percentage of cell death in A-549 lung cancer cells treated with PLA-PEG-Apt/DOX NPs at w/w ratio 10:1 is 3.19 and 8.34 fold higher than in non-targeted form and Free DOX treated cancer cells, respectively. Therefore, PLA-PEG-Apt/DOX NPs might be considered a promising drug delivery system for targeted drug delivery towards MUC1-overexpressing tumors cells.
Assuntos
Neoplasias Pulmonares , Nanopartículas , Apoptose , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mucina-1 , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/químicaRESUMO
Tissue plasminogen activator (tPA) a thrombolytic agent is commonly used for digesting the blood clot. tPA half-life is low (4-6â min) and its administration needs a prolonged continuous infusion. Improving tPA half-life could reduce enzyme dosage and enhance patient compliance. Nano-carries could be used as delivery systems for the protection of enzymes physically, enhancing half-life and increasing the stability of them. In this study, chitosan (CS) and polyethylene glycol (PEG) were used for the preparation of CS-g-PEG/tPA nanoparticles (NPs) via the ion gelation method. Particles' size and loading capacity were optimised by central composite design. Then, NPs cytotoxicity, release profile, enzyme activity and in vivo half-life and coagulation time were investigated. The results showed that NPs does not have significant cytotoxicity. Release study revealed that a burst effect happened in the first 5â min and resulted in releasing 30% of tPA. Loading tPA in NPs could decrease 25% of its activity but the half-life of it increases in comparison to free tPA in vivo. Also, blood coagulation time has significantly affected (p-value = 0.041) by encapsulated tPA in comparison to free tPA. So, CS-g-PEG/tPA could increase enzyme half-life during the time and could be used as a non-toxic candidate delivery system for tPA.
Assuntos
Quitosana , Nanopartículas , Portadores de Fármacos , Meia-Vida , Humanos , Polietilenoglicóis , Ativador de Plasminogênio TecidualRESUMO
Developing nanostructures for cancer treatment is growing significantly. Liposomal doxorubicin is a drug that is used in the clinic and represents a lot of benefits over doxorubicin. The development of multifunctional liposomes with different cancer treatment capability enables broader applications of doxorubicin chemotherapy. Many efforts were carried to prepare more effective liposomal formulation through loading gold nanoparticles (GNPs) in the formulation. Here, GNPs with an average size of 6â nm were loaded in liposomal formulation alongside doxorubicin. The hydrodynamic diameter of final formulation was 177.3 ± 33.9â nm that in comparison with liposomes without GNPs (112.5 ± 10.3â nm), GNPs-loaded liposomes showed the bigger hydrodynamic diameter. GNPs-loaded liposomes are slightly positively charged (4.4 ± 1.1â mV), while liposomes without loading the GNPs were negatively charged (-18.5 ± 1.6â mV). Doxorubicin was loaded in this formulation through active loading technique. Doxorubicin loading efficiency in gold-loaded liposomes is slightly lesser than liposomes without GNPs, but still considerably high in comparison to passive loading techniques.
Assuntos
Doxorrubicina/análogos & derivados , Portadores de Fármacos/síntese química , Ouro/química , Nanopartículas Metálicas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/síntese química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Hidrodinâmica , Lipossomos/síntese química , Lipossomos/química , Lipossomos/farmacocinética , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Espectrofotometria UltravioletaRESUMO
N-Acetylcysteine (NAC) loaded PLGA nanoparticles were prepared by electrospray method. The influence of independent parameters such as concentration, flow rate and nozzle to collector distance was studied on particle size and size distribution of generated nanoparticles using a Box-Behnken experimental design. Smallest size was found to be obtained at minimum value for both flow rate and concentration of polymer, regardless of collecting distance value in the ranges studied. Additionally, the minimum value of size distribution was observed at lowest values of both concentration of polymer and collecting distance, regardless of flow rate value. In total, a sample with minimum size and polydispersity was predicted to have flow rate, polymer concentration and collecting distance values of 0.06(ml/h), 0.5(%w/w) and 9.28(cm), respectively. The experimentally prepared nanoparticles with lowest size and size distribution values, had a size of 122(nm) and size distribution of 24. Zeta potential, drug loading and encapsulation efficiency of optimized nanoparticles were -6.58, 5% and 54.5%, respectively.