RESUMEN
Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions. This study uses formulation-based spray dry encapsulation technology to develop polymer-based PB-lithocholic acid (LCA) nanoparticles and assesses their efficacy in the 661W photoreceptor-like cell line. Incorporating LCA enhances nanoparticles' biological efficacy without compromising PB stability. In vitro studies demonstrate that PB-LCA nanoparticles prevent reactive oxygen species (ROS)-induced oxidative stress by improving cellular viability through the nuclear erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. These findings propose PB-LCA nanoparticles as a promising therapeutic strategy for oxidative stress-induced retinopathies.
Asunto(s)
Antioxidantes , Ácido Litocólico , Nanopartículas , Estrés Oxidativo , Polímeros , Probucol , Especies Reactivas de Oxígeno , Probucol/farmacología , Probucol/administración & dosificación , Probucol/química , Estrés Oxidativo/efectos de los fármacos , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Ácido Litocólico/química , Ácido Litocólico/farmacología , Animales , Polímeros/química , Línea Celular , Antioxidantes/farmacología , Antioxidantes/química , Factor 2 Relacionado con NF-E2/metabolismo , Supervivencia Celular/efectos de los fármacos , Ratones , Hemo-Oxigenasa 1/metabolismo , HumanosRESUMEN
Hearing loss impacts a large proportion of the global population. Damage to the inner ear, in particular the sensitive hair cells, can impact individuals for the rest of their lives. There are very limited options for interventions after damage to these cells has occurred. Targeted gene delivery may provide an effective means to trigger appropriate differentiation of progenitor cells for effective replacement of these sensitive hair cells. There are several hurdles that need to be overcome to effectively deliver these genes. Nanoencapsulation technology has previously been used for the delivery of pharmaceuticals, proteins and nucleic acids, and may provide an effective means of delivering genes to trigger appropriate differentiation. This review investigates the background of hearing loss, current advancements and pitfalls of gene delivery, and how nanoencapsulation may be useful.
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Oído Interno , Pérdida Auditiva , Humanos , Ácidos y Sales Biliares , Oído Interno/metabolismo , Pérdida Auditiva/genética , Pérdida Auditiva/metabolismo , Pérdida Auditiva/terapia , Técnicas de Transferencia de Gen , Terapia GenéticaRESUMEN
Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides' pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.
Asunto(s)
Biguanidas/química , Biguanidas/farmacología , Ácidos y Sales Biliares/química , Portadores de Fármacos , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Nanomedicina Teranóstica , Enfermedad Crónica/tratamiento farmacológico , Desarrollo de Medicamentos , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Metformina/administración & dosificación , Metformina/farmacocinética , Nanomedicina Teranóstica/métodosRESUMEN
Despite a relatively low prevalence of primary brain tumors, they continuously attract scientific interest because of the complexity of their treatment due to their location behind the blood-brain barrier. The main challenge in treatment of brain tumors is not the efficacy of the drugs, per se, but the low efficiency of drug delivery to malignant cells. At the core of the problem is the complex structure of the blood-brain barrier. Nowadays, there is evidence supporting the claim that bile acids have the ability to cross the blood-brain barrier. That ability can be exploited by taking a part in novel drug carrier designs. Bile acids represent a drug carrier system as a part of a mixed micelle composition, bilosomes and conjugates with various drugs. This review discusses the current knowledge related to bile acid molecules as drug penetration modifying agents, with the focus on central nervous system antitumor drug delivery.
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Antineoplásicos/metabolismo , Ácidos y Sales Biliares/metabolismo , Barrera Hematoencefálica/metabolismo , Fármacos del Sistema Nervioso Central/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/metabolismo , Animales , Antineoplásicos/administración & dosificación , Ácidos y Sales Biliares/administración & dosificación , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Barrera Hematoencefálica/efectos de los fármacos , Fármacos del Sistema Nervioso Central/administración & dosificación , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
Bile acids (BAs) are amphiphilic compounds and of recently have demonstrated wide range of formulation stabilizing effects. A recent study showed that primary un-metabolised bile acids (PUBAs) have ß-cell protective effects, and synergistic antidiabetic effects when combined with antioxidant and anti-inflammatory drugs, such as probucol (PB). Thus, this study aimed to design and test microcapsules containing a PUBA incorporated with PB and an alginate-Eudragit matrix. Six types of microcapsules were developed without (control) or with (test) PUBA, and tested for internal and external features and ß-cell protective effects. The incorporation of PB-alginate-Eudragit with PUBA produced stable microcapsules but did not exert consistent positive effects on cell viability in the hyperglycaemic state, which suggests that PUBA in alginate-Eudragit matrices did not exhibit synergistic effects with PB nor exerted antidiabetic effects.
RESUMEN
Studies in our laboratory have shown potential applications of the anti-atherosclerotic drug probucol (PB) in diabetes due to anti-inflammatory and ß-cell protective effects. The anti-inflammatory effects were optimized by incorporation of the anti-inflammatory bile acid, ursodeoxycholic acid (UDCA). This study aimed to test PB absorption, tissue accumulation profiles, effects on inflammation and type 1 diabetes prevention when combined with UDCA. Balb/c mice were divided into three equal groups and gavaged daily PB powder, PB microcapsules or PB-UDCA microcapsules for one week, at a constant dose. Mice were injected with a single dose of intraperitoneal/subcutaneous alloxan to induce type-1 diabetes and once diabetes was confirmed, treatments were continued for 3 days. Mice were euthanized and blood and tissues collected for analysis of PB and cytokine levels. The PB-UDCA group showed the highest PB concentrations in blood, gut, liver, spleen, brain, and white adipose tissues, with no significant increase in pancreas, heart, skeletal muscles, kidneys, urine or feces. Interferon gamma in plasma was significantly reduced by PB-UDCA suggesting potent anti-inflammatory effects. Blood glucose levels remained similar after treatments, while survival was highest among the PB-UDCA group. Our findings suggest that PB-UDCA resulted in best PB blood and tissue absorption and reduced inflammation.
Asunto(s)
Antiinflamatorios/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Células Secretoras de Insulina/efectos de los fármacos , Probucol/uso terapéutico , Ácido Ursodesoxicólico/uso terapéutico , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Combinación de Medicamentos , Composición de Medicamentos , Excipientes/química , Ratones Endogámicos BALB C , Tamaño de la Partícula , Probucol/administración & dosificación , Probucol/farmacocinética , Distribución Tisular , Ácido Ursodesoxicólico/administración & dosificación , Ácido Ursodesoxicólico/farmacocinéticaRESUMEN
INTRODUCTION: Ideal cell-containing microcapsules should be capable of maintaining cell viability and exhibit significant structural stability to support cellular functionality. To date, such microcapsules remain unavailable; thus, this study used our well-established microencapsulating methods to examine a total of 32 different microencapsulating formulations and correlate polymers' molecular weights (Mwt) and UDCA addition, with cell viability and microcapsules' stability, postmicroencapsulation. METHODS: MIN6 mouse-cloned pancreatic ß-cells were microencapsulated using control (n = 16; without UDCA) and test (n = 16; with UDCA) different polymers. Confocal microscopic imaging, cell viability, and microcapsules' stability were assessed. RESULTS: Best cell viability (>50%) was obtained at average Mwt of 50,000 g/mol (poly-l-ornithine), followed by 110,000 g/mol (poly-l-lysine). There was no linear correlation between Mwt and viability. Confocal imagining showed similar microcapsules' shape and cell distribution among all different polymers' molecular weights, which suggests that the microencapsulating method was efficient and maintained microcapsules' uniformity. UDCA addition resulted in enhanced osmotic stability of the microcapsules and improved cell viability, when the formulation contained 1% polylornithine, 1% polyethylene glycol, 20% Eudragit® NM30D, 1% polytetrafluoroethylene, or 5% pentamethylcyclopentasiloxane. CONCLUSIONS: UDCA addition improved microenvironmental conditions within the microcapsules but this effect was largely dependent on the polymer systems used.
Asunto(s)
Cápsulas/química , Cápsulas/farmacología , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus/tratamiento farmacológico , Células Secretoras de Insulina/efectos de los fármacos , Ósmosis/efectos de los fármacos , Polímeros/química , Animales , Materiales Biocompatibles/química , Línea Celular , Composición de Medicamentos/métodos , Ratones , Peso Molecular , Polietilenglicoles/química , Ácidos Polimetacrílicos/química , Politetrafluoroetileno/químicaRESUMEN
In previous studies, we developed a new technique (ionic gelation vibrational jet flow; IGVJF) in order to encapsulate pancreatic ß-cells, for insulin in vivo delivery, and diabetes treatment. The fabricated microcapsules showed good morphology but limited cell functions. Thus, this study aimed to optimize the IGVJF technique, by utilizing integrated electrode tension, coupled with high internal vibration, jet-flow polymer stream rate, ionic bath-gelation concentrations, and gelation time stay. The study also utilized double inner/outer nozzle segmented-ingredient flow of microencapsulating dispersion, in order to form ß-cell microcapsules. Furthermore, a microcapsule-stabilizing bile acid was added, and microcapsule's stability and cell functions measured. Buchi-based built-in system utilizing IGVJF technology was screened to produce best microcapsule-containing ß-cells with or without a stabilizing-enhancing bile acid. Formed microcapsules were examined, for physical characteristics, and encapsulated cells were examined for survival, insulin release, and inflammatory profiles. Optimized microencapsulating parameters, using IGJVF, were: 1000 V voltage, 2500 Hz frequency, 1 mL/min flow rate, 3% w/v ionic-bath gelation concentration, and 20 min gelation time. Microcapsules showed good morphology and stability, and the encapsulated cells showed good survival, and insulin secretion, which was optimized by the bile acid. Deployed IGVJF-based microencapsulating parameters utilizing stability-enhancing bile acid produced best microcapsules with best pancreatic ß-cells functions and survival rate, which, suggests potential application in cell transplantation.
Asunto(s)
Ácidos y Sales Biliares/farmacología , Biotecnología/métodos , Composición de Medicamentos/métodos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Animales , HumanosRESUMEN
PURPOSE: Recently we demonstrated that microencapsulation of a murine pancreatic ß-cell line using an alginate-ursodeoxycholic acid (UDCA) matrix produced microcapsules with good stability and cell viability. In this study, we investigated if translation of this formulation to microencapsulation of primary ß-cells harvested from mature double-transgenic healthy mice would also generate stable microcapsules with good cell viability. METHODS: Islets of Langerhans were isolated from Ngn3-GFP/RIP-DsRED mice by intraductal collagenase P digestion and density gradient centrifugation, dissociated into single cells and the ß-cell population purified by Fluorescence Activated Cell Sorting. ß-cells were microencapsulated using either alginate-poly-l-ornithine (F1; control) or alginate-poly-l-ornithine-UDCA (F2; test) formulations. Microcapsules were microscopically examined and microencapsulated cells were analyzed for viability, insulin and cytokine release, 2 days post-microencapsulation. RESULTS: Microcapsules showed good uniformity and morphological characteristics and even cell distribution within microcapsules with or without UDCA. Two days post microencapsulation cell viability, mitochondrial ATP and insulin production were shown to be optimized in the presence of UDCA whilst production of the proinflammatory cytokine IL-1ß was reduced. Contradictory to our previous studies, UDCA did not reduce production of any other pro-inflammatory biomarkers. CONCLUSIONS: These results suggest that UDCA incorporation improves microcapsules' physical and morphological characteristics and improves the viability and function of encapsulated mature primary pancreatic ß-cells.
Asunto(s)
Cápsulas , Citocinas/metabolismo , Células Secretoras de Insulina/citología , Insulina/metabolismo , Imagen Individual de Molécula/métodos , Alginatos/química , Animales , Supervivencia Celular , Citocinas/análisis , Composición de Medicamentos , Femenino , Glucosa/metabolismo , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Insulina/análisis , Células Secretoras de Insulina/metabolismo , Interleucina-1beta/metabolismo , Islotes Pancreáticos/metabolismo , Ratones Transgénicos , Microscopía , Péptidos/química , Ácido Ursodesoxicólico/químicaRESUMEN
PURPOSE: The encapsulation of pancreatic ß-cells in biocompatible matrix has generated great interest in diabetes treatment. Our work has shown improved microcapsules when incorporating the bile acid ursodeoxycholic acid (UDCA), in terms of morphology and cell viability although cell survival remained low. Thus, the study aimed at incorporating the polyelectrolytes polyallylamine (PAA) and poly-l-ornithine (PLO), with the polymer sodium alginate (SA) and the hydrogel ultrasonic gel (USG) with UDCA and examined cell viability and functionality post microencapsulation. METHODS: Microcapsules without (control) and with UDCA (test) were produced using 1% PLO, 2.5% PAA, 1.8% SA and 4.5% USG. Pancreatic ß-cells were microencapsulated and the microcapsules' morphology, surface components, cellular and bile acid distribution, osmotic and mechanical stability as well as biocompatibilities, insulin production, bioenergetics and the inflammatory response were tested. RESULTS: Incorporation of UDCA at 4% into a PLO-PAA-SA formulation system increased cell survival (p < 0.01), insulin production (p < 0.01), reduced the inflammatory profile (TNF-α, IFN-Ï, IL-6 and IL-1ß; p < 0.01) and improved the microcapsule physical and mechanical strength (p < 0.01). CONCLUSIONS: ß-cell microencapsulation using 1% PLO, 2.5% PAA, 1.8% SA, 4.5% USG and the bile acid UDCA (4%) has good potential in cell transplantation and diabetes treatment.
Asunto(s)
Alginatos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Células Secretoras de Insulina/citología , Ácido Ursodesoxicólico/química , Animales , Línea Celular , Supervivencia Celular , Células Inmovilizadas/citología , Células Inmovilizadas/metabolismo , Células Inmovilizadas/trasplante , Composición de Medicamentos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/trasplante , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ratones , Presión Osmótica , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: In a recent study, we developed a new microencapsulating method for ß-cell microencapsulation, but cell viability declined rapidly, post microencapsulation, due to potential polymer-polyelectrolyte chelation and non-porous microcapsules' membranes resulting in cell apoptosis. Thus, this study tested the effects of incorporating cationic polyamine at 1% w/v, on microcapsule strength and cell viability, in the absence or presence of an anionic tertiary bile acid (ATBA) with potential cell-protective effects. METHODS: 1% w/v polyamine was used without or with ATBA, to form ß-cell microcapsules and physical and biological analyses was carried out 50 h post microencapsulation. RESULTS: Microcapsules containing 1% w/v polyamine showed weak physical properties and low cell viability and ATBA incorporation resulted in >30% reduction in cell viability and increased levels of pro-inflammatory cytokines. CONCLUSION: Neither 1% w/v polyamine nor the presence of ATBA resulted in optimised cell viability, but rather reduced cell viability, enhanced inflammation and lowered insulin secretion.
Asunto(s)
Alilamina , Ácidos y Sales Biliares , Diabetes Mellitus/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Células Secretoras de Insulina/metabolismo , Alilamina/química , Alilamina/farmacocinética , Alilamina/farmacología , Ácidos y Sales Biliares/química , Ácidos y Sales Biliares/farmacocinética , Ácidos y Sales Biliares/farmacología , Cápsulas , Línea Celular , HumanosRESUMEN
CONTEXT: We previously designed, developed and characterized a novel microencapsulated formulation as a platform for the targeted delivery of Probucol (PB) in an animal model of Type 2 Diabetes. OBJECTIVE: The objective of this study is to optimize this platform by incorporating Chenodeoxycholic acid (CDCA), a bile acid with good permeation-enhancing properties, and examine its effect in vitro. Using sodium alginate (SA), we prepared PB-SA (control) and PB-CDCA-SA (test) microcapsules. RESULTS AND DISCUSSION: CDCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained unchanged. PB-CDCA-SA microcapsules showed good excipients' compatibilities, as evidenced by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy studies. CDCA reduced microcapsule swelling at pH 7.8 at both 37 °C and 25 °C and improved PB-release. CONCLUSION: CDCA improved the characteristics and release properties of PB-microcapsules and may have potential in the targeted oral delivery of PB.
Asunto(s)
Alginatos/química , Ácido Quenodesoxicólico/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Probucol/química , Administración Oral , Ácidos y Sales Biliares/química , Rastreo Diferencial de Calorimetría , Cápsulas , Composición de Medicamentos , Estabilidad de Medicamentos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Polvos , Reología , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Temperatura , Viscosidad , Microtomografía por Rayos XRESUMEN
In previous studies carried out in our laboratory, a bile acid formulation exerted a hypoglycaemic effect in a rat model of type 1 diabetes (T1D). When the antidiabetic drug gliclazide was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-deoxycholic acid (G-DCA), with good structural properties, excipient compatibility and which exhibited pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH controlled properties of this new formulation. The aim is also to examine the effect of DCA on G release kinetics at various pH values and different temperatures. Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared including: G-SA (control) and G-DCA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, 3, 7.4 and 7.8 and temperatures of 25 °C and 37 °C. The new formulation is further optimised by the addition of DCA. DCA reduced bead-swelling of the microcapsules at pH 7.8 and 3 at 25 °C and 37 °C, and even though bead size remains similar after DCA addition, the percentage of G release was enhanced at high pH values (pH 7.4 and 7.8, p < 0.01). The new formulation exhibits colon-targeted delivery and the addition of DCA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and DCA to the lower intestine.
Asunto(s)
Ácido Desoxicólico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Gliclazida , Hipoglucemiantes , Alginatos/química , Alginatos/farmacocinética , Alginatos/farmacología , Animales , Cápsulas , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacocinética , Ácido Desoxicólico/farmacología , Gliclazida/química , Gliclazida/farmacocinética , Gliclazida/farmacología , Ácido Glucurónico/química , Ácido Glucurónico/farmacocinética , Ácido Glucurónico/farmacología , Ácidos Hexurónicos/química , Ácidos Hexurónicos/farmacocinética , Ácidos Hexurónicos/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , RatasRESUMEN
INTRODUCTION: In previous studies, we have shown that a gliclazide-cholic acid derivative (G-CA) mixture resulted in an enhanced ileal permeation of G (ex vivo). When administered orally to diabetic rats, it brought about a significant hypoglycaemic effect. In this study, we aim to create a novel microencapsulated-formulation of G-CA with uniform and coherent structure that can be further tested in our rat model of type 1 diabetes (T1D). We also aim to examine the effect of CA addition to G microcapsules in the morphology, structure and excipients' compatibility of the newly designed microcapsules. METHOD: Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Complete characterizations of microcapsules were carried out. RESULTS: The new G-CA-SA formulation is further optimized by the addition of CA exhibiting pseudoplastic-thixotropic rheological characteristics. Bead size remains similar after CA addition, the new microcapsules show no chemical interactions between the excipients and this was supported further by the spectral studies suggesting bead stability. CONCLUSION: The new microencapsulated-formulation has good and uniform structural properties and may be suitable for oral delivery of antidiabetic-bile acid formulations.
Asunto(s)
Alginatos/química , Ácido Cólico/química , Portadores de Fármacos/química , Gliclazida/administración & dosificación , Hipoglucemiantes/administración & dosificación , Administración Oral , Animales , Cápsulas , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Composición de Medicamentos/métodos , Excipientes/química , Ácido Glucurónico/química , Ácidos Hexurónicos/química , RatasRESUMEN
In previous studies, we developed and characterised multicompartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in type 2 diabetes (T2D). We also designed a new microencapsulated formulation of probucol-sodium alginate (PB-SA), with good structural properties and excipient compatibility. The aim of this study was to examine the stability and pH-dependent targeted release of the microcapsules at various pH values and different temperatures. Microencapsulation was carried out using a Büchi-based microencapsulating system developed in our laboratory. Using SA polymer, two formulations were prepared: empty SA microcapsules (SA, control) and loaded SA microcapsules (PB-SA, test), at a constant ratio (1:30), respectively. Microcapsules were examined for drug content, zeta potential, size, morphology and swelling characteristics and PB release characteristics at pH 1.5, 3, 6 and 7.8. The production yield and microencapsulation efficiency were also determined. PB-SA microcapsules had 2.6 ± 0.25% PB content, and zeta potential of -66 ± 1.6%, suggesting good stability. They showed spherical and uniform morphology and significantly higher swelling at pH 7.8 at both 25 and 37°C (p < 0.05). The microcapsules showed multiphasic release properties at pH 7.8. The production yield and microencapsulation efficiency were high (85 ± 5 and 92 ± 2%, respectively). The PB-SA microcapsules exhibited distal gastrointestinal tract targeted delivery with a multiphasic release pattern and with good stability and uniformity. However, the release of PB from the microcapsules was not controlled, suggesting uneven distribution of the drug within the microcapsules.
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Cápsulas/síntesis química , Preparaciones de Acción Retardada/síntesis química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Probucol/administración & dosificación , Probucol/química , Administración Oral , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/química , Líquidos Corporales/química , Cápsulas/administración & dosificación , Preparaciones de Acción Retardada/administración & dosificación , Difusión , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Humanos , Concentración de Iones de Hidrógeno , TemperaturaRESUMEN
Aim: Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability and inner ear barriers hinder effective SNHL treatment. Methodology: We addressed this by developing probucol-loaded nanoparticles with polymers and lithocholic acid and tested them on House Ear Institute-Organ of Corti cells. Results: Probucol-based nanoparticles effectively reduced oxidative stress-induced apoptosis, enhanced cellular viability, improved probucol uptake and promoted mitochondrial function. Additionally, they demonstrated the capacity to reduce reactive oxygen species through the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Conclusion: This innovative nanoparticle system holds the potential to prevent oxidative stress-related hearing impairment, providing an effective solution for SNHL.
Hearing loss affects millions of people worldwide, and its prevalence is expected to double by 2050. Current treatments have limitations, pushing researchers to explore new options. Oxidative stress is a key player in hearing loss and is known to damage inner ear hair cells. While antioxidants, known for their protective effects, hold promise, delivering them effectively to the inner ear is challenging. Scientists have been testing nanoparticles loaded with the antioxidant probucol to fight hearing loss. In this study, these particles protected inner ear cells in cell studies, offering potential hope for preventing hearing problems. This research is a significant step toward finding better treatments for hearing loss.
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Oído Interno , Pérdida Auditiva Sensorineural , Nanopartículas , Humanos , Probucol/farmacología , Estrés Oxidativo , Antioxidantes/farmacología , Pérdida Auditiva Sensorineural/terapiaRESUMEN
Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood-brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevention and treatment. Preclinical investigations have unveiled multifaceted cellular effects of probucol, showcasing its remarkable antioxidative and anti-inflammatory properties, its ability to fortify the BBB and its direct influence on neural preservation and adaptability. These diverse effects collectively translate into enhancements in both motor and cognitive functions. This review provides a comprehensive overview of recent findings highlighting the efficacy of probucol and probucol-related compounds in the context of various neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and cognitive impairment associated with diabetes.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Probucol/uso terapéutico , Barrera HematoencefálicaRESUMEN
Aim: The aim of this study is to test the biocompatibility of hydrogels with polysaccharides and bile acids on three murine cell lines. Materials & methods: Novel hydrogels containing poloxamer 407, polysaccharides (starch, pectin, acacia, carboxymethyl and methyl 2-hydroxyethyl cellulose) and deoxycholic acid were prepared using cold method, sterilized and used in biological assays to determine effects on hepatic, muscle, and pancreatic beta cells. Results and conclusion: Hydrogels with deoxycholic acid had tissue-depending effects on cellular survival and bioenergetics, resulting in the best cellular viability and bioenergetics within pancreatic beta cells. Further research is needed as proposed hydrogels may be beneficial for cell delivery systems of pancreatic beta cells.
In this study, we made gels using different materials, including five types of sugar and an acid found in bile. We investigated whether these gels would harm cells and their respiration. Muscle cells responded poorly to gels, as gels harmed their natural processes. Liver cells responded slightly better to gels, but gels still harmed them a lot. Cells found in the pancreas were not especially affected by gels, and these gels may be good candidates for further research with pancreatic cells. The gels could potentially be used to deliver drugs to the cells.
RESUMEN
Bile acids play important roles in the human body, and changes in their pool can be used as markers for various liver pathologies. In addition to their functional effects in modulating inflammatory responses and cellular survivability, the unconjugated or conjugated, secondary, or primary nature of bile acids accounts for their various ligand effects. The common hydrophilic bile acids have been used successfully as local treatment to resolve drug-induced cell damage or to ameliorate hearing loss. From various literature references, bile acids show concentration and tissue-dependent effects. Some hydrophobic bile acids act as ligands modulating vitamin D receptors, muscarinic receptors, and calcium-activated potassium channels, important proteins in the inner ear system. Currently, there are limited resources investigating the therapeutic effects of bile acid on hearing loss and little to no information on detecting bile acids in the remote ear system, let alone baseline bile acid levels and their prevalence in healthy and disease conditions. This review presents both hydrophilic and hydrophobic human bile acids and their tissue-specific effects in modulating cellular integrity, thus considering the possible effects and extended therapeutic applicability of bile acids to the inner ear tissue.