RESUMEN
The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.
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Barrera Hematoencefálica , Nanopartículas , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Lípidos , LiposomasRESUMEN
The purpose of the current study was to prepare and characterize the targeted solid lipid nanoparticles (SLNs) containing docetaxel (DTX) for prostate cancer treatment. The goal has been achieved by locating anisamide (Anis) ligand on the surface of SLNs, which can interact with the overexpressed sigma receptor on the prostate cancer cells. DTX loaded SLNs were prepared by high shear homogenization and ultra-sonication method and optimized by applying experimental design. The average particle size and the entrapment efficiency of the optimum DTX-SLN were 174 ± 9.1 nm and 83 ± 3.34%, respectively. The results of differential scanning calorimetry showed that DTX had been dispersed as amorphous in the nanocarriers. Scanning electron microscopy (SEM) images confirmed the nanoscale size and spherical shape of the nanoparticles. The cytotoxicity studies have demonstrated that IC50 of free drug, DTX-SLN and DTX-SLN-Anis was 0.25 ± 0.01, 0.23 ± 0.02, 0.12 ± 0.01 nM on PC3 cell line and 20.9 ± 3.89, 18.74 ± 7.43, and 14.68 ± 5.70 nM on HEK293 cell line, respectively. Targeted DTX-SLN-Anis was acted more effectively on prostate cancer cells in comparison to DTX-SLN and free drug. The results of this study have depicted that the anti-cancer drug loaded in targeted SLNs can be a promising way for cancer treatment. In addition, performing in-vivo studies will be complementary to these findings.
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Introduction: Indinavir (IDV) is a potent HIV protease inhibitor used in the treatment of human immunodeficiency virus (HIV). IDV is a weak base with limited aqueous solubility in its unprotonated form; therefore, solubility of IDV in the gastrointestinal tract fluids is the rate-limiting step of its absorption and onset of action. However, in many cases, drugs are not absorbed well in the gastrointestinal tract; polymer nanoparticles were recognized as an effective carrier system for drug encapsulation and are now studied as a vehicle for oral delivery of insoluble compounds. Preparation of methoxy poly (ethylene glycol)-poly (e-caprolactone) (mPEG-PCL) nanoparticles is among the strategies to overcome low bioavailability of drugs with poor aqueous solubility. Materials and method: The structure of the copolymers was characterized using 1H NMR, FTIR, DSC and GPC techniques. IDV loaded mPEG- PCL nanoparticles prepared by emulsification solvent evaporation method were optimized using D-optimal experimental design and were characterized by various techniques such as DLS, DSC, XRD, AFM and SEM. Using Caco-2 cells as a cellular model, we studied the cellular uptake and transport. Results: In vivo pharmacokinetic studies were performed in rats. The plasma AUC (0-t), t1/2 and Cmax of IDV-mPEG-PCL NPs were increased by 5.30, 5.57 and 1.37 fold compared to the IDV solution, respectively. Conclusion: The results of this study are promising for the use of biodegradable polymeric nanoparticles to improve oral drug delivery.
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Portadores de Fármacos/química , Indinavir/administración & dosificación , Indinavir/farmacocinética , Nanopartículas/química , Poliésteres/química , Polietilenglicoles/química , Administración Oral , Animales , Disponibilidad Biológica , Transporte Biológico , Células CACO-2 , Liberación de Fármacos , Humanos , Indinavir/química , Indinavir/metabolismo , Masculino , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Solubilidad , Distribución TisularRESUMEN
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-ß (Aß) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aß-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4âng/g-1âh) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur-NLCs in decreasing the hallmarks of Aß in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aß-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.
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Enfermedad de Alzheimer/tratamiento farmacológico , Curcumina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides , Animales , Antioxidantes/administración & dosificación , Antioxidantes/uso terapéutico , Encéfalo/metabolismo , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/tratamiento farmacológico , Curcumina/administración & dosificación , Curcumina/farmacocinética , Modelos Animales de Enfermedad , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/uso terapéutico , Hipocampo/efectos de los fármacos , Lípidos , Masculino , Nanoestructuras , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacocinética , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
Curcumin is a multitherapeutic agent with great therapeutic potential in central nervous system (CNS) diseases. In the current study, curcumin was encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the purpose of increasing brain accumulation. The preparation processes have been optimized using experimental design and multiobjective optimization methods. Entrapment efficiency of curcumin in SLNs and NLCs was found to be 82% ± 0.49 and 94% ± 0.74, respectively. The pharmacokinetic studies showed that the amount of curcumin available in the brain was significantly higher in curcumin-loaded NLCs (AUC0-t = 505.76 ng/g h) compared to free curcumin (AUC0-t = 0.00 ng/g h) and curcumin-loaded SLNs (AUC0-t = 116.31 ng/g h) ( P < 0.005), after intravenous (IV) administration of 4 mg/kg dose of curcumin in rat. The results of differential scanning calorimetry and X-ray diffraction showed that curcumin has been dispersed as amorphous in the nanocarriers. Scanning electron microscopy images confirmed the nanoscale size and spherical shape of the nanoparticles. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging study indicated that preparation processes do not have any significant effect on the antioxidant activity of curcumin. The results of this study are promising for the use of curcumin-loaded NLCs in more studies and using curcumin in the treatment of CNS diseases.
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Curcumina/farmacología , Portadores de Fármacos/farmacología , Lípidos/química , Nanoestructuras/química , Animales , Disponibilidad Biológica , Encéfalo/efectos de los fármacos , Química Farmacéutica , Curcumina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Masculino , Nanopartículas/química , Ratas Sprague-DawleyRESUMEN
A highly sensitive electrochemical sensor for the detection of trichloroacetic acid (TCA) is developed by subsequent immobilization of phthalocyanine (Pc) and Fe(II) onto multiwalled carbon nanotubes (MWCNTs) modified glassy carbon (GC) electrode. The GC/MWCNTs/Pc/Fe(II) electrode showed a pair of well-defined and nearly reversible redox couple correspondent to (Fe(III)Pc/Fe(II)Pc) with surface-confined characteristics. The surface coverage (Γ) and heterogeneous electron transfer rate constant (ks) of immobilized Fe(II)-Pc were calculated as 1.26×10(-10) mol cm(-2) and 28.13 s(-1), respectively. Excellent electrocatalytic activity of the proposed GC/MWCNTs/Pc/Fe(II) system toward TCA reduction has been indicated and the three consequent irreversible peaks for electroreduction of CCl3COOH to CH3COOH have been clearly seen. The observed chronoamperometric currents are linearly increased with the concentration of TCA at concentration range up to 20mM. Detection limit and sensitivity of the modified electrode were 2.0 µM and 0.10 µA µM(-1) cm(-2), respectively. The applicability of the sensor for TCA detection in real samples was tested. The obtained results suggest that the proposed system can serve as a promising electrochemical platform for TCA detection.