RESUMEN
Globally, ischemic stroke is a leading cause of death and adult disability. Previous efforts to repair damaged brain tissue following ischemic events have been hindered by the relative isolation of the central nervous system. We have developed a gelatin nanoparticle-mediated intranasal drug delivery system as an efficient, non-invasive method for delivering 17ß-estradiol (E2) specifically to the brain, enhancing neuroprotection, and limiting systemic side effects. Young adult male C57BL/6 J mice subjected to 30 min of middle cerebral artery occlusion (MCAO) were administered intranasal preparations of E2-GNPs, water soluble E2, or saline as control 1 h after reperfusion. Following intranasal administration of 500 ng E2-GNPs, brain E2 content rose by 5.24 fold (P<0.0001) after 30 min and remained elevated by 2.5 fold at 2 h (P<0.05). The 100 ng dose of E2-GNPs reduced mean infarct volume by 54.3% (P<0.05, n=4) in comparison to saline treated controls, demonstrating our intranasal delivery system's efficacy.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Estradiol/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Nanopartículas/química , Administración Intranasal , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Estradiol/química , Gelatina/química , Gelatina/farmacología , Humanos , Infarto de la Arteria Cerebral Media/patología , Ratones , Neuroprotección/efectos de los fármacosRESUMEN
In this study, we investigated the effect of intracapsular environment on the survival of anchorage-dependent cells (ADCs) encapsulated in alginate microcapsules with three different core structures, i.e. liquid, semi-liquid and microsphere-encapsulating semi-liquid core, using NIH 3T3 fibroblasts as an ADC model. For the latter, we fabricated poly (É-caprolactone) microspheres and co-encapsulated them with the cells, to establish cell-substrate interactions in the capsule. The fibroblast cells co-encapsulated with the microspheres exhibited higher survival and growth than those without. This study provides a "proof of concept" for employing microspheres as a cell-friendly surface to establish intracapsular cell-substrate interactions thus prolonging the survival of encapsulated therapeutic ADCs.
Asunto(s)
Alginatos/química , Fibroblastos/citología , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Poliésteres/química , Animales , Cápsulas , Supervivencia Celular , Células Inmovilizadas/citología , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Ratones , Microesferas , Células 3T3 NIHRESUMEN
The therapeutic efficacy of intranasal iNOS siRNA delivery was investigated in the postischemic rat brain after encapsulating on in gelatin nanoparticles (GNPs; diameter 188.0 ± 60.9 nm) cross-linked with 0.0667% glutaraldehyde (GA). Intranasally delivered GNPs were found in extracellular and intracellular compartments of many brain regions, including the olfactory bulb, cerebral cortex, and striatum at 1 hour after infusion and continued to be detected for days. Infarct volumes were markedly suppressed (maximal reduction to 42.1 ± 2.6%) at 2 days after 60 minutes of middle cerebral artery occlusion (MCAO) when iNOS siRNA/GNPs were delivered at 6 hours post-MCAO. In addition, this protective effect was manifested by reductions in neurological and behavioral deficits that were sustained for 2 weeks. Therapeutic potency of iNOS siRNA/GNPs was significantly greater and sustained longer than that of bare siRNA and prolonged and efficient iNOS by iNOS siRNA/GNP is responsible for the robust neuroprotective effect.
Asunto(s)
Nanopartículas , Fármacos Neuroprotectores/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Administración Intranasal , Animales , Encéfalo , Gelatina , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , RatasRESUMEN
Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are left in the patient's body. Even though the first fluorescence-guided surgery was performed more than 50 years ago, it is still not accepted as a standard of care in part due to the lack of efficient and non-toxic targeted probes approved by regulatory agencies around the world. Herein, we report protease-activated cationic gelatin nanoparticles encapsulating indocyanine green (ICG) for the detection of primary breast tumors in murine models with high tumor-to-background ratios. Upon intravenous administration, these nanoprobes remain optically silent due to the energy resonance transfer among the bound ICG molecules. As the nanoprobes extravasate and are exposed to the acidic tumor microenvironment, their positive surface charges increase, facilitating cellular uptake. The internalized nanoprobes are activated upon proteolytic degradation of gelatin to allow high contrast between the tumor and normal tissue. Since both gelatin and ICG are FDA-approved for intravenous administration, this activatable nanoprobe can lead to quick clinical adoption and improve the treatment of patients undergoing image-guided cancer surgery.
RESUMEN
The ability of glucagon-like peptide-1 analogs to enhance glucose-dependent insulin secretion and to inhibit ß cell apoptosis could be of potential benefit for islet transplantation. In this study, we investigated the effect of sustained local delivery of exenatide, a synthetic exendin-4, on the in vitro viability and function of encapsulated porcine islets. Prior to encapsulation, we fabricated exenatide-loaded poly(latic-co-glycolic acid) microspheres, and investigated their release behavior with different initial drug-loading amounts. Exenatide-loaded microspheres, exhibiting a sustained release over 21 days, were subsequently chosen and co-encapsulated with porcine islets in alginate microcapsules. During the 21-day period, the islets co-encapsulated with the exenatide-loaded microspheres exhibited improved survival and glucose-stimulated insulin secretion, compared to those without. This suggested that the intracapsular sustained delivery of exenatide via microspheres could be a promising strategy for improving survival and function of microencapsulated porcine islets for islet xenotransplantation.
Asunto(s)
Alginatos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/química , Microesferas , Péptidos/administración & dosificación , Ponzoñas/administración & dosificación , Alginatos/química , Animales , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Exenatida , Ácido Glucurónico/administración & dosificación , Ácido Glucurónico/química , Ácidos Hexurónicos/administración & dosificación , Ácidos Hexurónicos/química , Hipoglucemiantes/química , Islotes Pancreáticos/efectos de los fármacos , Ácido Láctico/administración & dosificación , Ácido Láctico/química , Péptidos/química , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Porcinos , Ponzoñas/químicaRESUMEN
Novel macromolecular therapeutics such as peptides, proteins, and DNA are advancing rapidly toward the clinic. Because of typically low oral bioavailability, macromolecule delivery requires invasive methods such as frequently repeated injections. Parenteral depots including biodegradable polymer microspheres offer the possibility of reduced dosing frequency but are limited by the inability to adequately control delivery rates. To control release and investigate release mechanisms, we have encapsulated model macromolecules in monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres using a double-emulsion method in combination with the precision particle fabrication technique. We encapsulated fluorescein-dextran (F-Dex) and sulforhodamine B-labeled bovine serum albumin (R-BSA) into PLG microspheres of three different sizes: 31, 44, and 80 microm and 34, 47, and 85 microm diameter for F-Dex and R-BSA, respectively. The in vitro release profiles of both compounds showed negligible initial burst. During degradation and release, the microspheres hollowed and swelled at critical time points dependant upon microsphere size. The rate of these events increased with microsphere size resulting in the largest microspheres exhibiting the fastest overall release rate. Monodisperse microspheres may represent a new delivery system for therapeutic proteins and DNA and provide enhanced control of delivery rates using simple injectable depot formulations.
Asunto(s)
Portadores de Fármacos , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Polímeros/química , Química Farmacéutica , Preparaciones de Acción Retardada , Dextranos/química , Difusión , Composición de Medicamentos , Fluoresceínas/química , Colorantes Fluorescentes/química , Cinética , Microscopía Confocal , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Porosidad , Rodaminas/química , Albúmina Sérica Bovina/química , Solubilidad , Propiedades de Superficie , Tecnología Farmacéutica/métodosRESUMEN
Uniform biodegradable hydrogel microspheres (HMS) with precisely controlled size have been fabricated using an electric-field-assisted precision particle fabrication technique. Particle agglomeration was prevented by charging the hydrogel drops and allowing Coulomb repulsion to separate them. As a result, surfactant-free and non-toxic particle fabrication was possible and the resulting microspheres were most suitable for biomedical and food-related applications. Due to the size uniformity, the present HMS may serve as a convenient yet most accurate vehicle for controlled delivery of therapeutic agents and other active ingredients.
Asunto(s)
Materiales Biocompatibles/química , Quitosano/química , Sistemas de Liberación de Medicamentos , Hidrogeles/química , Microesferas , Electroquímica , Tamaño de la PartículaRESUMEN
Acute high-intensity physical exercise is known to improve cognitive performance of children, including those with attention-deficit/hyperactivity disorder (ADHD). In this work, we investigated the acute effect of an aerobic stretching and moderate-intensity, health and happiness improving movement (HHIM) exercise on the cortical activity of children with and without ADHD using electroencephalography (EEG). Children aged 12 to 14 yr with combined-type ADHD and age-matched healthy controls participated in the study, performing two individual movements (n=79, 35 controls) and a single exercise bout (n=45, 18 controls). electroencephalographic signals were recorded before and immediately after each movement, and before and after acute exercise under resting conditions, to obtain absolute and relative power estimates for the theta (3.5-8 Hz), alpha (8-12 Hz), sensory motor rhythm (12-16 Hz), and beta (16-25 Hz) bands. After acute HHIM exercise, all children showed significant changes in their relative EEG, mainly in the theta and alpha bands. Individual movements were found to influence relative theta, alpha and beta, and theta-to-beta ratios. He presents aerobic stretching HHIM exercise has demonstrated acute effect on the cortical activity of children.
RESUMEN
Addition of biodegradable polymer shells surrounding polymeric, drug-loaded microparticles offers the opportunity to control drug release rates. A novel fabrication method was used to produce microparticles with precise control of particle diameter and the thickness of the polymer shell. The effect of shell thickness on release of a model drug, piroxicam, has been clearly shown for 2- to 15-microm thick shells of poly(D,L-lactide) (PDLL) surrounding a poly(D,L-lactide-co-glycolide) (PLG) core and compared to pure PLG microspheres loaded with piroxicam. Furthermore, the core-shell microparticles are compared to microspheres containing blended polymers in the same mass ratios to demonstrate the importance of the core-shell morphology. Combining PDLL(PLG) microcapsules of different shell thicknesses allows nearly constant release rates to be attained for a period of 6 weeks.
Asunto(s)
Portadores de Fármacos/química , Ácido Láctico/química , Microesferas , Poliésteres/química , Ácido Poliglicólico/química , Polímeros/química , Química Farmacéutica , Preparaciones de Acción Retardada , Microscopía Confocal , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Piroxicam/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solubilidad , Factores de TiempoRESUMEN
Double-wall microspheres (DWMS), comprising distinct polymer core and shell phases, are useful and interesting for controlled-release drug delivery. In particular, the presence of a surface-eroding polymer core may be expected to limit water penetration and, therefore, delay degradation of the core phase and drug release. In this study, solid microspheres and DWMS were fabricated using a surface-eroding polymer (poly[1,6-bis(p-carboxyphenoxy)hexane]; PCPH) and a bulk-eroding polymer (poly(D,L-lactide-co-glycolide); PLG). Erosion of the particles was observed by optical and electron microscopy, while polymer degradation was followed by gel permeation chromatography, during incubation in buffer at 37 degrees C. Degradation and erosion were very different depending on which polymer formed the particle shell. Nevertheless, the relatively thin (approximately 5 microm) PCPH shells could not prevent water penetration, and the PLG cores completely eroded by 6 weeks of incubation.
Asunto(s)
Hexanos/química , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Polímeros/química , Cromatografía en Gel , Composición de Medicamentos , Estabilidad de Medicamentos , Excipientes , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Peso Molecular , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Improved control of surface micro- and nano-structure may lead to enhanced performance of degradable biomedical devices such as surgical dressings, vascular grafts, tissue engineering scaffolds, sutures, and structures for guided tissue regeneration. An electrohydrodynamic method called flow-limited field-injection electrostatic spraying (FFESS) has been developed as an improved technique for the controlled deposition of polymeric material. Injecting charge using a nano-sharpened tungsten needle in a process called field ionization can efficiently induce an ionic state in a solution of poly(D,L-lactide-co-glycolide) increasing its capacity to carry charge. As a result, sprays have been produced that are finer and more precisely controlled than sprays produced by conventional electrospraying techniques, which employ hypodermic needles as the spray nozzle. Here, the effect of FFESS variables including applied voltage, polymer solution flow rate, and solvent properties (surface tension, viscosity, vapor pressure) on spray performance have been qualitatively evaluated. Under certain conditions, increasing the applied voltage produced an increasingly rough surface morphology. Similarly, by reducing solvent surface tension and increasing solvent vapor pressure, more distinct surface structures could be formed including uniform nanoparticles. Working ranges of the important parameters for the production of specific structure types such as smooth or porous surfaces, non-woven or melded fibers, and distinct or melded nanoparticles have been defined. FFESS technology provides a simple yet powerful technique for fabricating biomedical devices with a precisely defined nano-structure potentially capable of utilizing a broad range of biocompatible polymeric materials.
Asunto(s)
Ácido Láctico/química , Nanoestructuras/química , Nanotecnología/métodos , Ácido Poliglicólico/química , Polímeros/química , Materiales Biocompatibles/química , Electricidad , Microscopía Electrónica de Rastreo , Nanoestructuras/ultraestructura , Nanotecnología/instrumentación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Reología , Solventes/química , Propiedades de Superficie , Tensión Superficial , ViscosidadRESUMEN
A thorough understanding of the factors affecting drug release mechanisms from surface-erodible polymer devices is critical to the design of optimal delivery systems. Poly(sebacic anhydride) (PSA) microspheres were loaded with three model drug compounds (rhodamine B, p-nitroaniline and piroxicam) with a range of polarities (water solubilities). The drug release profiles from monodisperse particles of three different sizes were compared to release from polydisperse microspheres. Each of the model drugs exhibited different release mechanisms. Drug distribution within the polymer was investigated by laser scanning confocal microscopy and scanning electron microscopy. Rhodamine, the most hydrophilic compound investigated, was localized strongly toward the microsphere surface, while the much more hydrophobic compound, piroxicam, distributed more evenly. Furthermore, all three compounds were most uniformly distributed in the smallest microspheres, most likely due to the competing effects of drug diffusion out of the nascent polymer droplets and the precipitation of polymer upon solvent extraction, which effectively "traps" the drug in the polymer matrix. The differing drug distributions were manifested in the drug release profiles. Rhodamine was released very quickly independent of microsphere size. Thus, extended release profiles may not be obtainable if the drug strongly redistributes in the microspheres. The release of p-nitroaniline was more prolonged, but still showed little dependence on microsphere size. Hence, when water-soluble drugs are encapsulated with hydrophobic polymers, it may be difficult to tailor release profiles by controlling microsphere size. The piroxicam-loaded microspheres exhibit the most interesting release profiles, showing that release duration can be increased by decreasing microsphere size, resulting in a more uniform drug distribution.
Asunto(s)
Anhídridos/química , Anhídridos/farmacocinética , Precipitación Química , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Microesferas , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/farmacocinéticaRESUMEN
As a leading cause of death and adult disability, ischemic stroke requires the development of non-invasive, long-acting treatments. Osteopontin (OPN) is an endogenous protein shown to have neuroprotective effects in the post-ischemic brain of rats when administered through the non-invasive, intranasal pathway. Previously, gelatin microspheres (GMSs) have been shown to enhance the neuroprotective effects of OPN when used as a carrier during instrastriatal administration, but GMSs are generally too large to enter the brain parenchyma following intranasal administration. Here, gelatin nanoparticles (GNPs) were investigated as a carrier for intranasal delivery of an OPN peptide for the treatment of ischemic stroke. We not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57 % reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.
RESUMEN
Gelatin microspheres (GMSs) are widely used as drug carriers owing to their excellent biocompatibilities and toxicologically safe degradation products. The drug release profile is easily tailored by controlling the cross-linking density and surface-to-volume ratio, i.e. size, of the GMS. In this study, we employed GMSs which are 25 µm in diameter and cross-linked with 0.03125% glutaraldehyde, to enable rapid initial and a subsequent sustained release. Therapeutic potency of human recombinant osteopontin (rhOPN) with or without encapsulation into GMSs was investigated after administrating them to rat stroke model (Sprague-Dawley; middle cerebral artery occlusion, MCAO). The administration of rhOPN/GMS (100 ng/100 µg) at 1h post-MCAO reduced the mean infarct volume by 81.8% of that of the untreated MCAO control and extended the therapeutic window at least to 12h post-MCAO, demonstrating a markedly enhanced therapeutic potency for the use of OPN in the post-ischemic brain. Scanning electron microscopy micrographs revealed that GMSs maintained the three-dimensional shape for more than 5 days in normal brain but were degraded rapidly in the post-ischemic brain, presumably due to high levels of gelatinase induction. After encapsulation with GMS, the duration of OPN release was markedly extended; from the period of 2 days to 5 days in normal brain, and from 2 days to 4 days in the post-ischemic brain; these encompass the critical period for recovery processes, such as vascularization, and controlling inflammation. Together, these results indicate that GMS-mediated drug delivery has huge potential when it was used in the hyperacute period in the post-ischemic brain.
Asunto(s)
Materiales Biocompatibles , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Gelatina/administración & dosificación , Microesferas , Fármacos Neuroprotectores/farmacología , Osteopontina/farmacología , Animales , Ensayo de Inmunoadsorción Enzimática , Microscopía Electrónica de Rastreo , Fármacos Neuroprotectores/farmacocinética , Osteopontina/farmacocinética , RatasRESUMEN
Microencapsulation and controlled release of the biocontrol agent Pantoea agglomerans strain E325 (E325), an antagonist to the bacterial plant pathogen Erwinia amylovora that causes fire blight, a devastating disease of apple and pear, have been investigated. Uniform core-shell alginate microcapsules (AMCs), 60-300 µm in diameter, were fabricated to encapsulate E325 within the core, along with nutrients, to preserve viability and promote proliferation. Controlled release of E325 was achieved by separately adjusting alginate concentrations in the shell and core solutions, and by modifying the AMC size. Viability of E325 was monitored via fluorescent staining, revealing either lack of or minimal stress during or after encapsulation. Proliferation of E325 within AMCs, followed by their subsequent release, and colonization activities within confines of apple flowers were studied under different encapsulation conditions using rfp-labeled E325 to obtain highly promising results. This study provided a 'proof of concept' of the successful use of a microencapsulated biocontrol agent, E325, against E. amylovora, and could serve as a model for further studies on the development of effective plant disease management strategies.
Asunto(s)
Antibiosis , Erwinia amylovora/crecimiento & desarrollo , Malus/microbiología , Pantoea/fisiología , Enfermedades de las Plantas/microbiología , Alginatos/química , Cápsulas/química , Células Inmovilizadas/fisiología , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Enfermedades de las Plantas/prevención & controlRESUMEN
A diffusion-based model describing the drug release from a charged hydrogel (gelatin) microsphere undergoing enzymatic degradation is presented. The model elucidates the effect of glutaraldehyde, a crosslinking agent, on the release profile in terms of the initial drug distribution, diffusivity of the drug, degradation rate of gelatin and its ability to form polyionic complex with the drug. The model was validated by comparing with in vitro release of trypan blue, an acidic model drug, from basic gelatin microspheres. While drug release was not a simple function of glutaraldehyde concentration, the effective diffusivity was found to be inversely proportional to glutaraldehyde concentration in the form of a power function when the initial drug distribution was taken into consideration. For these reasons, the present model can accurately predict drug release with no adjustable parameters, given the collagenase concentration. The present model may help design certain release scenarios from biodegradable charged hydrogels for the oppositely charged drugs and biomolecules.
Asunto(s)
Colagenasas/química , Reactivos de Enlaces Cruzados/química , Portadores de Fármacos/química , Glutaral/química , Hidrogeles/química , Modelos Químicos , Preparaciones Farmacéuticas/química , Bibliotecas de Moléculas Pequeñas/química , Gelatina/química , Microesferas , Tamaño de la Partícula , Solubilidad , Azul de Tripano/químicaRESUMEN
High-quality epitaxial interfaces and delicate control over shape anisotropy make nanorod heterostructures (NRHs) with staggered band offsets efficient in separating and directing photogenerated carriers. Combined with versatile and scalable wet chemical means of synthesis, these salient features of NRHs are useful for improving both the performance and the cost-effectiveness of photovoltaics (PVs). However, inefficient carrier transport and extraction have imposed severe limitations, outweighing the benefits of enhanced charge separation. Hence integration of type II NRHs into PVs has thus far been unfruitful. Here, we demonstrate PVs that utilize NRHs as an extremely thin absorber between electron and hole transporting layers. In the limit approaching monolayer thickness, PVs incorporating NRHs have up to three times the short circuit current and conversion efficiency over devices made from their single-component counterparts. Comparisons between linear and curved NRHs are also made, revealing the importance of internal geometry and heterointerfacial area for enhanced contribution of charge-separated state absorption to photocurrent and in contacting charge transport layers.
RESUMEN
High mobility group box 1 (HMGB1) is a family of endogenous molecules that is released by necrotic cells and causes neuronal damages by triggering inflammatory processes. In the cerebral ischemic brain, sustained and regulated suppression of HMGB1 has been emerged as a therapeutic means to grant neuroprotection. HMGB1 consists of two HMG boxes (A and B) and an acidic C-terminal tail, and the A box peptide antagonistically competes with HMGB1 for its receptors. In the middle cerebral artery occlusion (MCAO) in rats, a murine model of transient cerebral ischemia, administration of HMGB1 A box intraparenchymally, after encapsulated in biodegradable gelatin microspheres (GMS), which enhances the stability of peptide inside and allows its sustained delivery, at 1 h, 3 h, or 6 h after MCAO, reduced mean infarct volumes by, respectively, 81.3%, 42.6% and 30.7% of the untreated MCAO-brain, along with remarkable improvement of neurological deficits. Furthermore, the administration of HMGB1 A box/GMS suppressed proinflammatory cytokine inductions more strongly than the injection of non-encapsulated HMGB1 A box. Given that insulted brains-like ischemia have enhanced gelatinase activity than the normal brain, our results suggest that GMS-mediated delivery of therapeutic peptides is a promising means to provide efficient neuroprotection in the postischemic brain.
Asunto(s)
Materiales Biocompatibles/química , Gelatina/química , Proteína HMGB1/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Microesferas , Animales , Materiales Biocompatibles/administración & dosificación , Encéfalo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Proteína HMGB1/administración & dosificación , Inmunohistoquímica , Ataque Isquémico Transitorio/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Uniform gelatin microspheres (GMS) of a wet size of 100 microm in diameter were fabricated by the electric field assisted precision particle fabrication (E-PPF) method and crosslinked with different glutaraldehyde (GA) concentrations to study the effect of the crosslinking density on drug release. The drug release profiles of the crosslinked GMS were studied along with the intraparticle drug distribution and the particle degradation characteristics. Due to the concentration gradient of GA along the diffusion path into the GMS, the crosslinking density is higher on the GMS surface, making it less susceptible to degradation. As a result, the GMS with higher GA concentrations (0.375-0.875%) exhibited a highly resistant surface toward enzymatic degradation. On the other hand, the amount of drug complexation at the surface decreases as the GA concentration increases, which can be attributed to the lowered basicity of gelatin caused by the increased crosslinking density. These factors collectively affect the drug release kinetics and give rise to similar release profiles for GMS above a GA concentration of 0.375%.
Asunto(s)
Reactivos de Enlaces Cruzados/química , Colorantes Fluorescentes/química , Gelatina/química , Glutaral/química , Microesferas , Azul de Tripano/química , Sistemas de Liberación de Medicamentos , Cinética , Tamaño de la PartículaRESUMEN
Uniform chitosan microspheres have been fabricated and weakly crosslinked for potential applications in colon-specific drug delivery. The effects of microsphere size, crosslinking density and electrostatic interactions between the drug and chitosan on drug release were studied, employing model drugs of different acidities. When the drug was basic, all chitosan spheres exhibited 100% release within 30 min. As the acidity of the drug increased, the release slowed down and depended on the crosslinking density and microsphere size. The release of weakly acidic drug was most suppressed for large spheres (35-38 microm), while the small spheres (23-25 microm) with higher crosslinking exhibited the most retention of highly acidic drug, indicating that they are a promising candidate for colon-specific delivery.