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1.
ACS Appl Mater Interfaces ; 16(26): 34409-34418, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38889207

RESUMEN

Nanosizing drug crystals has emerged as a successful approach to enabling oral bioavailability, as increasing drug crystal surface area improves dissolution kinetics and effective solubility. Recently, bottom-up methods have been developed to directly assemble nanosized crystals by leveraging polymer and surfactant excipients during crystallization to control crystal size, morphology, and structure. However, while significant research has investigated how polymers and other single additives inhibit or promote crystallization in pharmaceutical systems, there is little work studying the mechanistic interactions of multiple excipients on drug crystal structure and the extent of crystallinity, which can influence formulation performance. This study explores how the structure and crystallinity of a model hydrophobic drug crystal, fenofibrate, change as a result of competitive interfacial chemisorption between common nonionic surfactants (polysorbate 80 and sorbitan monooleate) and a surface-active polymer excipient (methylcellulose). Classical molecular dynamics simulations highlight how key intermolecular interactions, including surfactant-polymer complexation and surfactant screening of the crystal surface, modify the resulting crystal structure. In parallel, experiments generating drug nanocrystals in hydrogel thin films validate that drug crystallinity increases with an increasing weight fraction of surfactant. Simulation results reveal a connection between accelerated dynamics in the bulk crystal and the experimentally measured extent of crystallinity. To our knowledge, these are the first simulations that directly characterize structural changes in a drug crystal as a result of excipient surface composition and relate the experimental extent of crystallinity to structural changes in the molecular crystal. Our approach provides a mechanistic understanding of crystallinity in nanocrystallization, which can expand the range of orally deliverable small molecule therapies.


Asunto(s)
Cristalización , Fenofibrato , Simulación de Dinámica Molecular , Nanopartículas , Tensoactivos , Tensoactivos/química , Nanopartículas/química , Fenofibrato/química , Hexosas/química , Polisorbatos/química , Metilcelulosa/química , Propiedades de Superficie , Interacciones Hidrofóbicas e Hidrofílicas , Polímeros/química
2.
Mol Pharm ; 21(7): 3395-3406, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38836777

RESUMEN

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.


Asunto(s)
Liberación de Fármacos , Metilcelulosa , Hidróxido de Sodio , Solubilidad , Hidróxido de Sodio/química , Metilcelulosa/química , Metilcelulosa/análogos & derivados , Polímeros/química , Portadores de Fármacos/química , Química Farmacéutica/métodos , Composición de Medicamentos/métodos , Pirrolidinas/química
3.
Mol Pharm ; 21(7): 3375-3382, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38885189

RESUMEN

Recent work has shown that an amorphous drug-polymer salt can be highly stable against crystallization under hot and humid storage conditions (e.g., 40 °C/75% RH) and provide fast release and that these advantages depend on the degree of salt formation. Here, we investigate the salt formation between the basic drug lumefantrine (LMF) and several acidic polymers: poly(acrylic acid) (PAA), hypromellose phthalate (HPMCP), hypromellose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), Eudragit L100, and Eudragit L100-55. Salt formation was performed by "slurry synthesis" where dry components were mixed at room temperature in the presence of a small quantity of an organic solvent, which was subsequently removed. This method achieved more complete salt formation than the conventional methods of hot-melt extrusion and rotary evaporation. The acidic group density of a polymer was determined by nonaqueous titration in the same solvent used for slurry synthesis; the degree of LMF protonation was determined by X-ray photoelectron spectroscopy. The polymers studied show very different abilities to protonate LMF when compared at a common drug loading, following the order PAA > (HPMCP ∼ CAP ∼ L100 ∼ L100-55) > HPMCAS, but the difference largely disappears when the degree of protonation is plotted against the concentration of the available acidic groups for reaction. This indicates that the extent of salt formation is mainly controlled by the acidic group density and is less sensitive to the polymer architecture. Our results are relevant for selecting the optimal polymer to control the degree of ionization in amorphous solid dispersions.


Asunto(s)
Polímeros , Polímeros/química , Metilcelulosa/química , Metilcelulosa/análogos & derivados , Cristalización/métodos , Celulosa/química , Celulosa/análogos & derivados , Resinas Acrílicas/química , Sales (Química)/química , Derivados de la Hipromelosa/química , Solubilidad
4.
ACS Biomater Sci Eng ; 10(6): 3833-3841, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38747490

RESUMEN

This study explores the realm of personalized medicine by investigating the utilization of 3D-printed dosage forms, specifically focusing on patient-specific enteric capsules designed for the modified release of ketoprofen, serving as a model drug. The research investigates two distinct scenarios: the modification of drug release from 3D-printed capsules crafted from hydroxypropyl methylcellulose phthalate:polyethylene glycol (HPMCP:PEG) and poly(vinyl alcohol) (PVA), tailored for pH sensitivity and delayed release modes, respectively. Additionally, a novel ketoprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) based on pomegranate seed oil (PSO) was developed, characterized, and employed as a fill material for the capsules. Through the preparation and characterization of the HPMCP:PEG based filament via the hot-melt extrusion method, the study thoroughly investigated its thermal and mechanical properties. Notably, the in vitro drug release analysis unveiled the intricate interplay between ketoprofen release, polymer type, and capsule thickness. Furthermore, the incorporation of ketoprofen into the SNEDDS exhibited an enhancement in its in vitro cylooxygenase-2 (COX-2) inhibitory activity. These findings collectively underscore the potential of 3D printing in shaping tailored drug delivery systems, thereby contributing significantly to the advancement of personalized medicine.


Asunto(s)
Cápsulas , Liberación de Fármacos , Emulsiones , Cetoprofeno , Medicina de Precisión , Impresión Tridimensional , Cetoprofeno/química , Medicina de Precisión/métodos , Humanos , Emulsiones/química , Polietilenglicoles/química , Sistemas de Liberación de Medicamentos/métodos , Preparaciones de Acción Retardada , Metilcelulosa/química , Metilcelulosa/análogos & derivados , Alcohol Polivinílico/química
5.
Food Chem ; 453: 139683, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-38788649

RESUMEN

Methylcellulose (MC)/grape pomace (GP) films, plasticized with either glycerol (GLY) or cinnamon essential oil (CEO), were prepared by thermo-compression molding and characterized. Compared to the GLY-plasticized MC50/GP50 films, a considerable increase in TS and YM values of CEO-plasticized films was observed, rising from 9.66 to 30.05 MPa, 762 to 1631 MPa, respectively. Moreover, the water vapor barrier, surface hydrophobic properties, and antioxidant/antibacterial activities of CEO-plasticized films remarkedly improved with increasing CEO content from 5 to 15% w/w. From scanning electron microscopy, phase separation between GP and the MC/GLY mixture were evident for GLY-plasticized MC/GP films. On the other hand, the CEO-plasticized films showed compact morphologies, attributable to the formation of hydrogen bonding and π-π stacking interaction. Preliminary shelf-life study on showed that fresh chicken wrapped with the CEO-plasticized MC/GP films exhibited lower TVB-N, TBARS, and TVC values than the unwrapped control samples, during 7 d storage at 4 °C.


Asunto(s)
Antibacterianos , Antioxidantes , Embalaje de Alimentos , Metilcelulosa , Vitis , Antioxidantes/química , Antioxidantes/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Vitis/química , Embalaje de Alimentos/instrumentación , Metilcelulosa/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Animales , Pollos , Cinnamomum zeylanicum/química
6.
Int J Biol Macromol ; 270(Pt 2): 132189, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723812

RESUMEN

Intelligent packaging with freshness indication capability can help consumers purchase fresh food. However, current research primarily focuses on carbon dioxide-sensitive intelligent packaging, with limited research on water vapor-sensitive indication packaging. In this study, the water vapor-sensitive indicator membrane was prepared and used to determine the freshness of mushrooms. The results of this study showed that the water permeability of the indicator membrane decreased from 33.17 % to 21.59 % with the increase of Polyethylene glycol-400(PEG-400) content in methylcellulose(MC) membrane, and the contact angle of the indicator membrane increased from 87 % to 98 % with the addition of PEG-400. The addition of plasticizer PEG-400 increased the hydrophobicity of the indicator film, which could be attributed to the improvement of the molecular arrangement and crystallinity of the indicator film by the addition of PEG-400. After encountering water, the transparency of the indicator membrane changes from completely opaque (white) to transparent. Addition of PEG-400 reduces the rate of change in the transparency of the indicator membrane. The indicator membrane was successfully used to indicate the freshness of mushrooms and effectively reflected the freshness of mushrooms during storage. This technology could be applied to measure the freshness of other foods.


Asunto(s)
Embalaje de Alimentos , Membranas Artificiales , Metilcelulosa , Polietilenglicoles , Hongos Shiitake , Polietilenglicoles/química , Embalaje de Alimentos/métodos , Hongos Shiitake/química , Metilcelulosa/química , Vapor , Agua/química , Permeabilidad , Interacciones Hidrofóbicas e Hidrofílicas
7.
J Colloid Interface Sci ; 669: 975-983, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38759596

RESUMEN

HYPOTHESIS: Hydroxypropyl methylcellulose phthalate (HPMCP) is an enteric polymer that has been employed in drug delivery systems to delay the release of the encapsulated active pharmaceutical ingredients through its pH-responsive solubility change. This has been recently demonstrated as an effective means for delaying the drug release from gelatin/HPMCP hydrogels at gastric pH values. However, structural characteristics of HPMCP agglomeration in gelatin/HPMCP hydrogels is not well understood thus limiting further tailoring of their material properties. EXPERIMENTS: We investigated the multiscale structure of a gelatin/HPMCP hydrogel (1:1 by weight) between pH 2 and 6 at 37 °C, i.e. above the upper critical solution transition temperature of gelatin, using small-angle X-ray scattering and contrast-variation small-angle neutron scattering to understand the pH-responsive structure of HPMCP and the cross-correlation between gelatin and HPMCP. FINDINGS: Agglomeration of HPMCP between pH 2 and 4 was evidenced by the formation of mass fractal structures, with a fractal dimension ranging from 1.5 to 2.7, comprising primary particles with a radius of gyration ranging from 70 to 140 Å. Blending with gelatin influenced the fractal structure of HPMCP and the primary particle size. Gelatin and HPMCP exhibited negative cross-correlation in all probed length scales and pH values, which was attributed to volume-exclusion interaction in a double-network-like solution architecture.


Asunto(s)
Gelatina , Metilcelulosa , Tamaño de la Partícula , Dispersión del Ángulo Pequeño , Gelatina/química , Concentración de Iones de Hidrógeno , Metilcelulosa/química , Metilcelulosa/análogos & derivados , Hidrogeles/química , Estructura Molecular
8.
Int J Biol Macromol ; 269(Pt 2): 132270, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38734347

RESUMEN

Methylcellulose, a prominent polysaccharide prevalent in the food sector, was considered to fabricate the active films with glutaraldehyde as a crosslinker and Noni (Morinda citrifolia) Leaf Extract (NLE) as an active agent. FTIR analysis confirms the intermolecular -OH bonding, and SEM micrograms demonstrate methylcellulose active films' homogeneous, dense morphologic appearance. Due to the crosslinking effect of glutaraldehyde and noni leaf extract, tensile strength (41.83 ± 0.134 MPa) and crystallinity (62.91 %) of methylcellulose films were improved. Methylcellulose active films suppress water and moisture uptake at various relative humidities. The inhibition capability against foodborne pathogens and the excellent antioxidant activity [DPPH (93.191 ± 1.384 %) and ABTS (90.523 ± 1.412 %)] of NLE incorporation suggested that food packed in methylcellulose active films were effective against pathogenic and oxidative attacks. During preservation, to ensure the apple slices' nutritional values, they are covered with physiochemically enhanced methylcellulose active films for up to 120 h. The minimum reduction in vitamin C, reducing sugar content, percentage weight loss, pH, and total phenolic content of apple slices preserved in MGN active films at room temperature suggests it is an affordable and efficient replacement to traditional single-use plastic packaging in the cut fruit industry.


Asunto(s)
Antioxidantes , Embalaje de Alimentos , Malus , Metilcelulosa , Morinda , Extractos Vegetales , Hojas de la Planta , Morinda/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Embalaje de Alimentos/métodos , Antioxidantes/farmacología , Antioxidantes/química , Metilcelulosa/química , Malus/química
9.
Nat Commun ; 15(1): 4523, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806464

RESUMEN

Interest in gene therapy medicines is intensifying as the first wave of gene-correcting drugs is now reaching patient populations. However, efficacy and safety concerns, laborious manufacturing protocols, and the high cost of the therapeutics are still significant barriers in gene therapy. Here we describe liquid foam as a vehicle for gene delivery. We demonstrate that embedding gene therapy vectors (nonviral or viral) in a methylcellulose/xanthan gum-based foam formulation substantially boosts gene transfection efficiencies in situ, compared to liquid-based gene delivery. We further establish that our gene therapy foam is nontoxic and retained at the intended target tissue, thus minimizing both systemic exposure and targeting of irrelevant cell types. The foam can be applied locally or injected to fill body cavities so the vector is uniformly dispersed over a large surface area. Our technology may provide a safe, facile and broadly applicable option in a variety of clinical settings.


Asunto(s)
Terapia Genética , Vectores Genéticos , Terapia Genética/métodos , Vectores Genéticos/genética , Animales , Humanos , Ratones , Técnicas de Transferencia de Gen , Metilcelulosa/química , Transfección/métodos , Femenino , Polisacáridos Bacterianos
10.
Mol Pharm ; 21(6): 2908-2921, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38743928

RESUMEN

The physical stability of amorphous solid dispersions (ASDs) is a major topic in the formulation research of oral dosage forms. To minimize the effort of investigating the long-term stability using cost- and time-consuming experiments, we developed a thermodynamic and kinetic modeling framework to predict and understand the crystallization kinetics of ASDs during long-term storage below the glass transition. Since crystallization of the active phrarmaceutical ingredients (APIs) in ASDs largely depends on the amount of water absorbed by the ASDs, water-sorption kinetics and API-crystallization kinetics were considered simultaneously. The developed modeling approach allows prediction of the time evolution of viscosity, supersaturation, and crystallinity as a function of drug load, relative humidity, and temperature. It was applied and evaluated against two-year-lasting crystallization experiments of ASDs containing nifedipine and copovidone or HPMCAS measured in part I of this work. We could show that the proposed modeling approach is able to describe the interplay between water sorption and API crystallization and to predict long-term stabilities of ASDs just based on short-term measurements. Most importantly, it enables explaining and understanding the reasons for different and sometimes even unexpected crystallization behaviors of ASDs.


Asunto(s)
Cristalización , Agua , Cristalización/métodos , Agua/química , Cinética , Estabilidad de Medicamentos , Nifedipino/química , Compuestos de Vinilo/química , Termodinámica , Pirrolidinas/química , Viscosidad , Química Farmacéutica/métodos , Humedad , Temperatura , Solubilidad , Metilcelulosa/química , Metilcelulosa/análogos & derivados
11.
Cell Rep Methods ; 4(5): 100777, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38744289

RESUMEN

Human brain tissue models and organoids are vital for studying and modeling human neurological disease. However, the high cost of long-term cultured organoids inhibits their wide-ranging application. It is therefore urgent to develop methods for the cryopreservation of brain tissue and organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, and Y27632 (termed MEDY) for the cryopreservation of cortical organoids without disrupting the neural cytoarchitecture or functional activity. MEDY can be applied to multiple brain-region-specific organoids, including the dorsal/ventral forebrain, spinal cord, optic vesicle brain, and epilepsy patient-derived brain organoids. Additionally, MEDY enables the cryopreservation of human brain tissue samples, and pathological features are retained after thawing. Transcriptomic analysis shows that MEDY can protect synaptic function and inhibit the endoplasmic reticulum-mediated apoptosis pathway. MEDY will enable the large-scale and reliable storage of diverse neural organoids and living brain tissue and will facilitate wide-ranging research, medical applications, and drug screening.


Asunto(s)
Encéfalo , Criopreservación , Organoides , Humanos , Organoides/efectos de los fármacos , Criopreservación/métodos , Encéfalo/efectos de los fármacos , Encéfalo/citología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Glicol de Etileno/farmacología , Metilcelulosa/química , Metilcelulosa/farmacología , Dimetilsulfóxido/farmacología
12.
Water Sci Technol ; 89(7): 1846-1859, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619907

RESUMEN

Geosynthetic clay liners (GCLs) are mostly used as flow barriers in landfills and waste containments due to their low hydraulic conductivity to prevent the leachate from reaching the environment. The self-healing and swell-shrink properties of soft clays (expansive soils) such as bentonite enable them as promising materials for the GCL core layers. However, it is important to modify their physico-chemical properties in order to overcome the functional limitations of GCL under different hydraulic conditions. In the present study, locally available black cotton soil (BCS) is introduced in the presence of an anionic polymer named carboxymethyl cellulose (CMC) as an alternative to bentonite to enhance the hydraulic properties of GCL under different compositions. The modified GCL is prepared by stitching the liner with an optimum percentage of CMC along with various percentages of BCS mixed with bentonite. Hydraulic conductivity tests were performed on the modified GCL using the flexi-wall permeameter. The results suggest that the lowest hydraulic conductivity of 4.58 × 10-10 m/s is obtained when 25% of BCS is blended with bentonite and an optimum 8% CMC and further addition of BCS results in the reduction of the hydraulic conductivity.


Asunto(s)
Bentonita , Eliminación de Residuos , Bentonita/química , Arcilla , Suelo , Metilcelulosa , Eliminación de Residuos/métodos , Carboximetilcelulosa de Sodio
13.
Biochemistry (Mosc) ; 89(2): 201-211, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38622090

RESUMEN

Visomitin eye drops are the first and, so far, the only drug based on SkQ1 - the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl) decyltriphenylphosphonium, developed in the laboratories of Moscow State University under the leadership of Academician V. P. Skulachev. SkQ1 is considered as a potential tool to combat the aging program. We have previously shown that it is able to prevent and/or suppress development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to the age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations on progression of the AMD-like pathology and p38 MAPK and ERK1/2 activity in the OXYS rat retina (from the age of 9 to 12 months). Wistar and OXYS rats treated with placebo (composition identical to Visomitin with the exception of SkQ1) were used as controls. Ophthalmological examination showed that in the OXYS rats receiving placebo, retinopathy progressed and severity of clinical manifestations did not differ from the intact OXYS rats. Visomitin suppressed progression of the AMD-like pathology in the OXYS rats and significantly improved structural and functional parameters of the retinal pigment epithelium cells and state of microcirculation in the choroid, which, presumably, contributed to preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38 MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of the Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38 MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades.


Asunto(s)
Compuestos de Benzalconio , Sistema de Señalización de MAP Quinasas , Degeneración Macular , Metilcelulosa , Plastoquinona , Humanos , Ratas , Animales , Lactante , Ratas Wistar , Soluciones Oftálmicas/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/metabolismo , Envejecimiento/metabolismo , Transducción de Señal , Combinación de Medicamentos
14.
J Mater Chem B ; 12(18): 4427-4440, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38629219

RESUMEN

Injectable bone substitutes (IBSs) represent a compelling choice for bone tissue regeneration, as they can be exploited to optimally fill complex bone defects in a minimally invasive manner. In this context, in situ gelling methylcellulose (MC) hydrogels may be engineered to be free-flowing injectable solutions at room temperature and gels upon exposure to body temperature. Moreover, incorporating a suitable inorganic phase can further enhance the mechanical properties of MC hydrogels and promote mineralization, thus assisting early cell adhesion to the hydrogel and effectively guiding bone tissue regeneration. In this work, thermo-responsive IBSs were designed selecting MC as the organic matrix and calcium phosphate (CaP) or CaP modified with graphene oxide (CaPGO) as the inorganic component. The resulting biocomposites displayed a transition temperature around body temperature, preserved injectability even after loading with the inorganic components, and exhibited adequate retention on an ex vivo calf femoral bone defect model. The addition of CaP and CaPGO promoted the in vitro mineralization process already 14 days after immersion in simulated body fluid. Interestingly, combined X-ray diffraction and solid state nuclear magnetic resonance characterizations revealed that the formed biomimetic phase was constituted by crystalline hydroxyapatite and amorphous calcium phosphate. In vitro biological characterization revealed the beneficial impact of CaP and CaPGO, indicating their potential in promoting cell adhesion, proliferation and osteogenic differentiation. Remarkably, the addition of GO, which is very attractive for its bioactive properties, did not negatively affect the injectability of the hydrogel nor the mineralization process, but had a positive impact on cell growth and osteogenic differentiation on both pre-differentiated and undifferentiated cells. Overall, the proposed formulations represent potential candidates for use as IBSs for application in bone regeneration both under physiological and pathological conditions.


Asunto(s)
Regeneración Ósea , Hidrogeles , Metilcelulosa , Hidrogeles/química , Hidrogeles/farmacología , Regeneración Ósea/efectos de los fármacos , Metilcelulosa/química , Animales , Inyecciones , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Grafito/química , Bovinos , Proliferación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Humanos
15.
J Mater Chem B ; 12(21): 5171-5180, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38687592

RESUMEN

Advanced colorectal cancer (CRC) with peritoneal metastasis (PM) is a highly aggressive malignancy with poor prognosis. Systematic chemotherapy and local treatments are the primary therapeutic approaches. However, systemic chemotherapy is limited by low accumulation of drugs at the tumor site and systemic toxicity. Local treatments include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, CRS faces challenges related to incomplete tumor resection, while HIPEC is restricted by the uneven distribution of drugs and potential complications. Herein, a thermosensitive methyl-cellulose-based injectable hydrogel carrying oxaliplatin (OXA) was synthesized to improve this situation. Specifically, methyl cellulose (MC) coagulated into a hydrogel, and OXA was loaded into the MC hydrogel to construct the OXA-MC hydrogel. We explored the OXA-MC hydrogel for the treatment of PM in CRC. The results demonstrated that the OXA-MC hydrogel had favorable biocompatibility and thermo-sensitivity and could act as a local slow-release drug carrier. Moreover, in a CT-26 tumor-bearing model, it showed a remarkable anti-tumor effect by inhibiting proliferation and promoting apoptosis. Additionally, transcriptome analysis indicated that the OXA-MC hydrogel might be involved in the regulation of the PI3K-AKT signaling pathway. In summary, we successfully prepared the OXA-MC hydrogel and provided a valid approach in the treatment of PM in CRC, which lays a foundation for other PM treatments.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Hidrogeles , Metilcelulosa , Oxaliplatino , Neoplasias Peritoneales , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Oxaliplatino/química , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Hidrogeles/química , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Ratones , Metilcelulosa/química , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Apoptosis/efectos de los fármacos , Portadores de Fármacos/química , Temperatura , Ensayos de Selección de Medicamentos Antitumorales , Inyecciones
16.
J Biomater Sci Polym Ed ; 35(9): 1421-1438, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38536671

RESUMEN

The present research focuses on formulating and evaluating hydrogels modified with crosslinking agents using methylcellulose to treat diabetic foot ulcers (DFU). Methylcellulose hydrogels are prepared and characterized for their crosslinking capacity through FTIR and degradation studies. The optimized hydrogel is further assessed for viscosity, gel strength, contact angle, in-vitro biodegradation, water-vapor transmission rate, anti-bacterial activity, and in-vivo efficacy. The results demonstrate that the developed hydrogel exhibits promising properties for DFU treatment, including increased wound healing percentage, improved ulcer morphology, reduced levels of proinflammatory cytokines, and enhanced tissue characteristics. These findings suggest that the novel hydrogel composition could serve as a viable alternative to existing dressings for DFU management.


Asunto(s)
Pie Diabético , Hidrogeles , Metilcelulosa , Cicatrización de Heridas , Pie Diabético/terapia , Pie Diabético/tratamiento farmacológico , Animales , Metilcelulosa/química , Hidrogeles/química , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Viscosidad , Masculino , Ratas , Citocinas/metabolismo
17.
Int J Biol Macromol ; 264(Pt 1): 130628, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38453111

RESUMEN

Multifunctional packaging films that monitor and maintain fish freshness hold significant potential for use in the food industry. This study introduces a multifunctional intelligent packaging film comprising alizarin (ALI)-embedded cubic γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) (denoted as γ-CD-MOFs@ALI) in a methylcellulose/polyvinyl alcohol (MP)-based matrix to achieve colorimetric monitoring and enhanced preservation of fish freshness. The MP/γ-CD-MOFs@ALI reveals a rapid color transition in 3 min from yellow color progressively darkens to purple as the pH increases from 2.0 to 10.0. And it is proved that the as-prepared film owns high antibacterial activity against Gram-positive bacteria (S. aureus), impressive ABTS+ radical scavenging rates of 85.54 ± 1.25 %, and effective ALI sustained-release properties. The intelligent packaging film exhibits an excellent colorimetric response to total volatile basic nitrogen and provides exceptional freshness preservation performance, effectively prolonging the shelf life of Ctenopharyngodon idella (grass carp) under 25 °C to 42 h.


Asunto(s)
Antraquinonas , Carpas , Estructuras Metalorgánicas , gamma-Ciclodextrinas , Animales , Alcohol Polivinílico , Staphylococcus aureus , Metilcelulosa , Embalaje de Alimentos , Concentración de Iones de Hidrógeno , Antocianinas
18.
Int J Nanomedicine ; 19: 2807-2821, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38525014

RESUMEN

Background: Bufalin (BFL, an active anti-tumor compound derived from toad venom) is limited in its application due to high toxicity and rapid metabolism of the cardiotonic steroid. Ester prodrug self-assembly nanoparticles have shown significant improved effects in addressing the above-mentioned issues. Methods: An ester bond was formed between linoleic acid and bufalin to synthesize linoleic acid-bufalin prodrug (LeB). The self-assembly nanoparticles (LeB-PSNs) containing different mass ratios of DSPE-PEG2k and prodrug (6:4, 7:3, 8:2, 9:1 and 10:0) were prepared via co-precipitation method and defined as 6:4-PSNs, 7:3-PSNs, 8:2-PSNs, 9:1-PSNs and LeB-PSNs, respectively. Further, the characterization (particle size, zeta potential, surface morphology and stability) of the nanoparticles was carried out. Finally, we evaluated the impact of different ratios of DSPE-PEG2k on the hydrolysis rate, cytotoxicity, cellular uptake, cell migration and proliferation suppression potential of the prodrug nanoparticles. Results: The linoleic acid-bufalin prodrug (LeB) was successfully synthesized. Upon the addition of DSPE-PEG2k at different weight ratios, both particle size and polydispersity index (PDI) significantly decreased, while the zeta potential increased remarkably. No significant differences in particle size, PDI and Zeta potential were observed among the 9:1, 8:2 and 7:3 PSNs. Notably, the 8:2 (w/w) DSPE-PEG2k nanoparticles exhibited superior stability, hydrolysis and cellular uptake rates, along with efficient cell cytotoxicity, cell migration and proliferation suppression. Conclusion: These findings indicate that DSPE-PEG2k could improve the performance of BFL prodrug nanoparticles, namely enhancing stability and achieving adaptive drug release by modulating the hydrolysis rate of esterase. This study therefore provides more opportunities for the development of BFL application.


Asunto(s)
Nanopartículas , Fosfatidiletanolaminas , Profármacos , Profármacos/farmacología , Profármacos/química , Portadores de Fármacos/química , Ácido Linoleico , Polietilenglicoles/química , Nanopartículas/química , Movimiento Celular , Proliferación Celular , Metilcelulosa
19.
Int J Biol Macromol ; 263(Pt 2): 130539, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38432263

RESUMEN

Hydroxypropyl methylcellulose (HPMC) was employed as an intermediate layer to enhance interfacial interaction between chitosan (CS) coating and tangerine fruits, thereby improving the preservation effect. Owing to the low surface tension of tangerine fruit (26.04 mN/m), CS coating solutions showed poor wetting properties on fruit peels (contact angle > 100°). However, by applying a 1.0 % (w/v) HPMC coating on fruits, the contact angle of CS solutions with concentrations of 0.5 %, 1.0 %, and 1.5 % (w/v) decreased to 47.0°, 47.4°, and 48.5°, respectively, whereas the spreading coefficient increased to -16.0 mN/m, -17.6 mN/m and -19.8 mN/m, respectively. Subsequently, the effects of the coatings on fruit quality were investigated. The results demonstrated the promising performance of HPMC-CS two-layer coating in inhibiting fruit respiration, reducing decay rate, and maintaining nutrient content. Notably, HPMC-1.5%CS coating not only reduced the decay rate of tangerine fruit by 45 % and 31 %, in comparison to the uncoated group (CK) and pure CS coating respectively, but also maintained a high content of ascorbic acid. Therefore, this study confirmed that the use of amphiphilic polymers for improving the surface properties of fruits can effectively facilitate the wetting of hydrophilic coatings on fruits, and significantly improve the fresh-keeping performance of edible coatings.


Asunto(s)
Quitosano , Citrus , Humectabilidad , Derivados de la Hipromelosa , Frutas , Conservación de Alimentos/métodos , Metilcelulosa
20.
J Biomater Sci Polym Ed ; 35(6): 869-879, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38310516

RESUMEN

The dressing materials that provide surface protection, bacteriostatic activities, and tissue regeneration are important for the treatment and management of complex wounds. This study aimed to evaluate the wound-healing properties of electrospun nanofibers containing a blend of methylcellulose (MC) and polyvinyl alcohol (PVA). The nanofibers were tested in single-layered (S-NFs) and multilayered (M-NFs) forms (PCL/MC-PVA/PCL). In vitro scratch assay using L929 cells and in vivo experiments on Wistar rats were conducted. The results showed that both S-NFs and M-NFs significantly accelerated wound closure by promoting cell migration. M-NFs demonstrated superior wound healing activity compared to S-NFs. Additionally, M-NFs exhibited faster skin epithelization compared to S-NFs. Histopathological evaluation confirmed the absence of irritation or lesions on the healed wound surface. Overall, the study concluded that these polymeric nanofibers have the potential to be used as self-wound healing dressings. They are safe, non-toxic, biodegradable, and biocompatible.


Asunto(s)
Nanofibras , Poliésteres , Alcohol Polivinílico , Ratas , Animales , Metilcelulosa , Ratas Wistar , Vendajes , Antibacterianos
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