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1.
Ecotoxicol Environ Saf ; 202: 110935, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800218

RESUMO

This study investigated the ability of dual crosslinked interpenetrating polymer network (IPN) blend beads (DIN:SA/PVA-beads), composed of sodium alginate (SA) and poly (vinyl alcohol) (PVA), as a base-triggered carrier for the controlled release of dinotefuran (DIN) in Spodoptera litera midgut. The blend beads were characterized for morphology, encapsulation efficiency, swelling degree, and in vitro release of the blend beads were characterized. The results revealed that the double-crosslinked gel beads had a tightly interpenetrating network structure and exhibited a satisfactory embedding effect for DIN. The maximum of the DIN loading capacity was approximately 1.01%, with a high encapsulation efficiency of 83.19%. The triggered release of DIN from the blend beads was studied in deionized water (pH 3.0-11.0) via high-performance liquid chromatography (HPLC); it was found that the release rate was higher in alkaline pH conditions than in acidic and neutral conditions. An in vivo dynamics and degradation study also demonstrated that the excellent release characteristics of DIN:SA/PVA-beads in the midgut of S. litera. This study provides a promising controlled-release form of dinotefuran that is more effective and can be used for the targeted control of pests with alkaline midgut.


Assuntos
Guanidinas/metabolismo , Neonicotinoides/metabolismo , Nitrocompostos/metabolismo , Spodoptera/metabolismo , Alginatos/química , Animais , Preparações de Ação Retardada/química , Etanol , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Polímeros , Álcool de Polivinil/química
2.
PLoS One ; 15(6): e0234544, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555670

RESUMO

Controlled-release and slow-release fertilizers can effectively supply nitrogen (N) while mitigating N loss. To determine the suitability of these fertilizers for plants in semi-arid environments, these fertilizers need to be evaluated under varying placement and temperature conditions. Several urea fertilizers were evaluated, including: uncoated, sulfur-coated (SCU), polymer-coated-sulfur-coated (PCSCU), and polymer-coated (PCU) with projected release timings between 45 and 180 d. Nitrogen release was measured under daily fluctuating or static temperatures applied either to the surface or buried in the soil. A second experiment consisted of two PCU sources and added a hanging bag placement comparison and low and high soil moisture treatments. For the first Experiment, the N in uncoated urea released shortly after application. The SCU and PCSCU treatments released > 80% of the N before the first sampling date. With fluctuating temperatures, the PCU 45, 75, 120, and 180 incorporated into the soil released N within +9, +9, -22, and -68 d of their expected timing. However, they released their N within 35 d when surface applied. Conversely, with static temperatures, PCU products released slowly, releasing under 80% for the entire study. The second experiment verified these results and showed no difference between low and high moisture and minimal release with fertilizer not in contact with soil. Each coated fertilizer in these studies exhibited slow/control release properties, but the PCU (surface applied) and SCU/PCSCU (surface applied or incorporated in soil) release was much more rapid than expected. Our research suggests that, although the SCU and PCSCU showed minimal slow-release properties (regardless of placement), the PCU fertilizers incorporated in the soil do have a controlled release approximate to what is expected, but have a much more rapid release when surface applied.


Assuntos
Agricultura , Preparações de Ação Retardada/farmacologia , Fertilizantes , Nitrogênio/farmacologia , Preparações de Ação Retardada/química , Nitrogênio/química , Polímeros/química , Solo/química , Enxofre/química , Temperatura , Ureia/química , Ureia/farmacologia
3.
AAPS PharmSciTech ; 21(4): 126, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382992

RESUMO

Orally dissolving films (ODFs) have received much attention as potential oral drug delivery systems for paediatric and geriatric patients, particularly those suffering from dysphagia. With their unique properties and advantages, the technology offers improved patient compliance and wider acceptability, eliminates the fear of choking, enables ease of administration and offers dosing convenience, without the requirement of water. However, adequate drug loading remains a challenge. The aim of this study was to mechanistically design and evaluate fast and extended release ODF formulations with high drug loading capacity, displaying good physicochemical and mechanical properties, as a potential dosage form for paediatric and geriatric use employing a slightly soluble model drug-ibuprofen. Different polymers (0.6-10% HPMC, 0.6-1.5% guar gum), plasticisers (0.1-0.5% glycerine, 0.1% sorbitol) and processing conditions (40-60°C drying temperatures, 8-16 h drying times) were investigated to produce films using the solvent casting method. Molecular compatibility was assessed using TGA, XRD and FTIR whereas film topography was assessed using SEM. Maximum ibuprofen load in single films was 20.7 mg/film (54.4%) and released 100% drug content in 5 min, while triple layered ibuprofen-loaded films contained 62.2 mg/film and released 100% drug release in 1 h. The ODFs demonstrated good disintegration time using low volume artificial saliva media and high dosage from uniformity. This study provides a mechanistic insight to the design and evaluation of fast and extended release ODFs with high drug loading, suitable for administration to paediatric and geriatric patients.


Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ibuprofeno/química , Ibuprofeno/metabolismo , Administração Oral , Idoso , Criança , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Geriatria , Humanos , Ibuprofeno/administração & dosagem , Pediatria , Solubilidade , Difração de Raios X/métodos
4.
AAPS PharmSciTech ; 21(5): 148, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32436061

RESUMO

The aim of this study was to evaluate the potential of a cross-linked pregelatinized potato starch (PREGEFLO® PI10) as matrix former for controlled release tablets. Different types of tablets loaded with diprophylline, diltiazem HCl or theophylline were prepared by direct compression of binary drug/polymer blends. The drug content was varied from 20 to 50%. Two hydroxypropyl methylcellulose grades (HPMC K100LV and K100M) were studied as alternative matrix formers. Drug release was measured in a variety of release media using different types of experimental set-ups. This includes 0.1 N HCl, phosphate buffer pH 6.8 and water, optionally containing different amounts of NaCl, sucrose, ethanol or pancreatin, fasted state simulated gastric fluid, fed state simulated gastric fluid, fasted state simulated intestinal fluid, fed state simulated intestinal fluid as well as media simulating the conditions in the colon of healthy subjects and patients suffering from Crohn's disease. The USP apparatuses I/II/III were used under a range of operating conditions and optionally coupled with the simulation of additional mechanical stress. Importantly, the drug release kinetics was not substantially affected by the investigated environmental conditions from tablets based on the cross-linked pregelatinized potato starch, similar to HPMC tablets. However, in contrast to the latter, the starch-based tablets roughly kept their shape upon exposure to the release media (they "only" increased in size) during the observation period, and the water penetration into the systems was much less pronounced. Thus, the investigated cross-linked pregelatinized potato starch offers an interesting potential as matrix former in controlled release tablets.


Assuntos
Preparações de Ação Retardada/química , Solanum tuberosum/química , Amido/química , Diltiazem/química , Liberação Controlada de Fármacos , Gelatina/química , Humanos , Derivados da Hipromelose/química , Comprimidos/química , Teofilina/química
6.
Nature ; 579(7799): 421-426, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32188939

RESUMO

Bioorthogonal chemistry capable of operating in live animals is needed to investigate biological processes such as cell death and immunity. Recent studies have identified a gasdermin family of pore-forming proteins that executes inflammasome-dependent and -independent pyroptosis1-5. Pyroptosis is proinflammatory, but its effect on antitumour immunity is unknown. Here we establish a bioorthogonal chemical system, in which a cancer-imaging probe phenylalanine trifluoroborate (Phe-BF3) that can enter cells desilylates and 'cleaves' a designed linker that contains a silyl ether. This system enabled the controlled release of a drug from an antibody-drug conjugate in mice. When combined with nanoparticle-mediated delivery, desilylation catalysed by Phe-BF3 could release a client protein-including an active gasdermin-from a nanoparticle conjugate, selectively into tumour cells in mice. We applied this bioorthogonal system to gasdermin, which revealed that pyroptosis of less than 15% of tumour cells was sufficient to clear the entire 4T1 mammary tumour graft. The tumour regression was absent in immune-deficient mice or upon T cell depletion, and was correlated with augmented antitumour immune responses. The injection of a reduced, ineffective dose of nanoparticle-conjugated gasdermin along with Phe-BF3 sensitized 4T1 tumours to anti-PD1 therapy. Our bioorthogonal system based on Phe-BF3 desilylation is therefore a powerful tool for chemical biology; our application of this system suggests that pyroptosis-induced inflammation triggers robust antitumour immunity and can synergize with checkpoint blockade.


Assuntos
Preparações de Ação Retardada/administração & dosagem , Neoplasias Mamárias Experimentais/imunologia , Piroptose/imunologia , Animais , Cumarínicos/administração & dosagem , Cumarínicos/química , Cumarínicos/metabolismo , Cumarínicos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Preparações de Ação Retardada/farmacocinética , Feminino , Proteínas de Fluorescência Verde/administração & dosagem , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Fluorescência Verde/farmacocinética , Células HeLa , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/química , Imunoconjugados/metabolismo , Imunoconjugados/farmacocinética , Inflamassomos/imunologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/administração & dosagem , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacocinética , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas/administração & dosagem , Proteínas/química , Proteínas/metabolismo , Proteínas/farmacocinética , Silanos/administração & dosagem , Silanos/química , Silanos/metabolismo , Silanos/farmacocinética , Linfócitos T/imunologia , Trastuzumab/administração & dosagem , Trastuzumab/química , Trastuzumab/metabolismo , Trastuzumab/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Mater Sci Eng C Mater Biol Appl ; 108: 110466, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923948

RESUMO

Essentially, the human body can release in different disease conditions specific biomolecules such as histamines when the body encounters a toxic substance, antibodies which are part of the body's natural immune response or nitric oxide as a cardiovascular signalling molecule. Design and development of "intelligent" delivery systems able to release the therapeutic agent only in the presence of bioactive compounds was presented here. Poly(N-isopropylacrylamide-co-N-(3-aminopropyl)methacrylamide)) (poly(NIPAAm-co-APM)) was synthesized as an exciting pH/temperature sensitive copolymer. Under physiological conditions (pH = 7.4), the APM in copolymer is in the ionized state (pKa = 8.7), highly hydrophilic and therefore the copolymer loses thermosensitive properties. Remarkably, after electrostatic interactions of APM with specific biomolecules, the copolymer restores the thermosensitive property. Thus, the microgels synthesized from this copolymer are in the "inactivated" state at normal physiological pH and temperature (pH = 7.4 and T = 36 °C). In the presence of specific biomolecules, microgels undergo "activation", shrink and expel mechanically a certain amount of drug. It must be mentioned that the pH-sensitive component plays the role of a biosensor, the biomolecule acts as a triggering agent, and the poly(NIPAAm) represents the delivery component (actuator). MTT tests showed that poly(NIPAAm-co-APM) microspheres are completely devoid of toxicity; moreover, the rabbit dermal fibroblasts vastly adhere to the surface of microspheres.


Assuntos
Derme/metabolismo , Portadores de Fármacos , Fibroblastos/metabolismo , Teste de Materiais , Animais , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Derme/citologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Fibroblastos/citologia , Concentração de Íons de Hidrogênio , Coelhos
8.
Mater Sci Eng C Mater Biol Appl ; 108: 110432, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923974

RESUMO

Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and inner diameter of 180 ± 48 nm and 106 ± 30 nm, respectively. Thermal gravimetric analysis determines that the mass loss of the core-sheath fibers fall between the mass loss values of individual sheath and core fibers. Swelling studies indicate higher water absorption of the core-sheath mat compared to the separate sheath and core membranes. In vitro drug release studies in Phosphate Buffered Saline (PBS) determine sustained release of the therapeutics from the core-sheath structure. The release trails three stages including non-Fickian diffusion at the early stage followed by the Fickian diffusion mechanism. The present study shows a useful approach to design core-sheath nanofibrous membranes with controlled and programmable drug release profiles.


Assuntos
Gelatina , Muramidase , Nanofibras/química , Fenitoína , Álcool de Polivinil , Animais , Linhagem Celular , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Gelatina/química , Gelatina/farmacologia , Camundongos , Muramidase/química , Muramidase/farmacocinética , Muramidase/farmacologia , Fenitoína/química , Fenitoína/farmacocinética , Fenitoína/farmacologia , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia
9.
Mater Sci Eng C Mater Biol Appl ; 108: 110461, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924029

RESUMO

A novel bio-responsive co-delivery system based on Poly(DEA)-b-Poly(ABMA-co-OEGMA) (PDPAO, prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization) copolymers was constructed for enhanced cellular internalization and effective combination therapy. Reduction-sensitive 6-mercaptopurine (6MP) based prodrug and pH-sensitive doxorubicin (DOX) based prodrug were grafted onto PDPAO by an azide-alkyne "Click Chemistry" reaction to acquire a pH/reduction-sensitive polymeric prodrug (PDPAO@imine-DOX/cis-6MP), which was able to self-aggregate to form polymeric micelles (M(DOX/6MP)) with an average particle size of 116 ± 2 nm in the water. The resultant micelles could maintain a stable sphere structure and show stability with a small particles' dispersion index in the blood. Importantly, it has been observed that the pH-sensitive surface charge-conversion accompanied pH-triggered DOX release in the biomimetic extracellular acidic environment of tumor tissue and a rapid dual-drug release triggered by pH and GSH in the intracellular environment. The in vitro evaluation of micelles on human cervical cancer (HeLa) and human promyelocytic leukemia (HL-60) cells showed an enhanced cellular uptake because of charge-conversion and exhibited a higher cell-killing performance. Moreover, the graft ratio of DOX and 6MP showed the ability to adjust the cytotoxicity; the micelles with a graft ratio of 2: 1 (M(DOX2/6MP)) displayed the higher cellular inhibition on either HeLa (combination index (CI) = 0.62) or HL-60 (CI = 0.35) cells. Overall, this novel dual-drug-conjugated delivery system might have important potential applications for combination therapy of cancer.


Assuntos
Química Click , Doxorrubicina , Portadores de Fármacos , Mercaptopurina , Neoplasias/tratamento farmacológico , Pró-Fármacos , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Células HL-60 , Células HeLa , Humanos , Mercaptopurina/química , Mercaptopurina/farmacologia , Neoplasias/metabolismo , Neoplasias/patologia , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia
10.
Mater Sci Eng C Mater Biol Appl ; 108: 110459, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924031

RESUMO

In this work, a new pH-responsive nanohybrid carrier was prepared with chelating ZnO-dopamine (Zn-d) on the surface of graphene oxide. Doxorubicin (DOX) as a model drug was loaded on the resulted nanohybrid. The characteristics of Zn-d-rGO nanohybrid (NH) determined using Fourier transformed infrared spectroscopy (FT-IR), X-ray Diffraction spectroscopy (XRD), UV-Visible spectroscopy, Scanning Electron Microscope (SEM), EDX and AFM. The BET analysis showed a specific surface area of 37.16 m2/g and the obtained nanohybrid indicated a high loading capacity of DOX up to 99.7%, and the release profile displayed a pH-dependent discharge in the acidic environment for14 days. The cytotoxicity of the prepared nanohybrid was measured against T47D and MCF10A cells and it confirmed that as-prepared nanohybrid has high toxicity against cancer cells and lower effect against human breast cell. Meanwhile, the prepared nanohybrids showed well antimicrobial activity against gram-positive and negative bacteria. The obtained results showed that the prepared nanohybrid (Zn-d-rGO) could potentially be used as a safe carrier for drug delivery systems.


Assuntos
Antibacterianos , Quelantes , Dopamina , Doxorrubicina , Portadores de Fármacos , Grafite , Nanopartículas/química , Óxido de Zinco , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Quelantes/química , Quelantes/farmacocinética , Quelantes/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Dopamina/química , Dopamina/farmacocinética , Dopamina/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Grafite/química , Grafite/farmacocinética , Grafite/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Óxido de Zinco/química , Óxido de Zinco/farmacocinética , Óxido de Zinco/farmacologia
11.
Mater Sci Eng C Mater Biol Appl ; 108: 110455, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924042

RESUMO

An amphiphilic biodegradable branched copolymer, mPEG-b-PLGA-g-OCol, was synthesized by grafting copolymer (methoxy polyethylene glycol)-b-Poly (l,d-lactic-co-glycolic acid) (mPEG-b-PLGA) on oligomeric collagen (OCol), to form a branched structure with mPEG-b-PLGA as side chain and OCol as backbone. mPEG-b-PLGA and mPEG-b-PLGA-g-OCol were both amphipathic and can self-assemble into micelles in aqueous solution. The mPEG-b-PLGA-g-OCol micelles showed pH-sensitive behaviors and the particle size below 100 nm in slightly acidic environment such as tumor tissue milieu interieur to perform passive targeting. Observed by SEM, when the solution pH increased from 5 to 9, the morphology of mPEG-b-PLGA-g-OCol micelles changed from small spheres to larger ones to rings. For biodegradable mPEG-b-PLGA-g-OCol, the micelles will gradually degrade in body. Further, doxorubicin (DOX) was effectively loaded in the micelles with drug loading and encapsulation efficiency of 3.48% and 25.8%, respectively. To evaluate antineoplastic effect of DOX-laden micelles in vitro, MTT test, flow cytometry and CLSM were performed and found that DOX-laden micelles exhibited higher cellular proliferation inhibition against HeLa cells. These features indicated that the mPEG-b-PLGA-g-OCol micelles were potential drug carrier for cancer therapy.


Assuntos
Plásticos Biodegradáveis , Portadores de Fármacos , Micelas , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacocinética , Plásticos Biodegradáveis/farmacologia , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Poliésteres/síntese química , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia
12.
Food Chem ; 314: 126204, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31978719

RESUMO

We examined the morphology of a network made with native BSA molecules being crosslinked with genipin at ambient temperature. Ninhydrin assay, FTIR, WAXD, SEM and mechanical tests documented successful crosslinking that enhanced the structural properties of the three dimensional structure. Its hydrophilic nature allows swelling with water absorption, which can be monitored with the modified Flory-Rehner theory to predict the molecular weight between adjacent crosslinks, network mesh size and crosslinking density as a function of crosslinker addition. Characterisation studies were carried out with a view to developing a delivery vehicle for the controlled release of vitamin B6 over a prolonged period of observation. Moving boundaries associated with swelling of the protein matrix resulted in vitamin transport that could be described with the interplay of diffusional and relaxational kinetics via the Peppas-Sahlin equation. Combination of diffusion and swelling equilibrium theories unveils a measurable effect of network characteristics on vitamin B6 release.


Assuntos
Iridoides/química , Soroalbumina Bovina/química , Vitamina B 6/química , Animais , Bovinos , Preparações de Ação Retardada/química , Difusão , Cinética , Peso Molecular
13.
J Food Sci ; 85(1): 143-149, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31945206

RESUMO

Development and utilization of oxygen absorbing materials for food and beverage packaging are important to protect the oxygen-sensitive foods. In this study, we developed a kind of ionic polymer with excellent oxygen absorbing ability based on reacting ethylene-acrylic acid copolymer (EAA) and sodium sulfite (Na2 SO3 ). By virtue of the hydrophilicity of the ionic polymer, the sulfite in Na2 SO3 is easily hydrolyzed and ionized. The oxygen inhalation reaction was gradually initiated and started, whereas achieved a slow and controllable oxygen absorption process. The oxygen absorbing agent can be directly added in the form of an auxiliary agent, which greatly simplifies the preparation process of the oxygen absorbing material. Furthermore, the ionic structure of the EAA/Na2 SO3 composites were destroyed and mechanical properties of the material did not decrease after oxygen absorption. More importantly, it can effectively prevent the entry of external oxygen because the ionic polymer itself has better barrier properties. PRACTICAL APPLICATION: Typical oxygen-sensitive objects include: beer, coffee, canned food, meat products, dairy products, and so on. The presence of oxygen in the package can cause microbial growth, odor generation, color change and nutrient loss, resulting in a significant reduction in food shelf life. Therefore, controlling the oxygen content of the food package is important to limit the rate of these spoilage and spoilage reactions in the food. Materials with active oxygen scavenging and good barrier properties and packaging performance are highly economically viable in terms of improving product quality and reducing packaging costs.


Assuntos
Preparações de Ação Retardada/química , Embalagem de Alimentos/instrumentação , Oxigênio/química , Polímeros/química , Animais , Conservação de Alimentos/métodos , Armazenamento de Alimentos , Produtos da Carne/análise , Sulfitos/química
14.
AAPS PharmSciTech ; 21(3): 83, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989330

RESUMO

Niacin (nicotinic acid, NA) is administered orally as an antihyperlipidemic agent in extended-release (ER) tablets in high doses. Due to rapid absorption and extensive metabolism (non-linear pharmacokinetics), the drug plasma levels are highly variable, which may correlate with side effects. Interestingly, this erratic drug delivery behavior of niacin ER products cannot be clarified by compendial in vitro release testing. The standard dissolution tests do not allow to mimic the selected GI tract characteristics in order to estimate the robustness of formulation under the variability of the physiological conditions. These are characterized by the pH value, impact of motility forces and composition, as well as volume of GI liquids. Our paper demonstrates a comparison of a newly developed ER HPMC niacin formulation with an originator product. The research aimed to design a robust matrix tablet of comparable biopharmaceutical behavior, safety and efficacy. The extensive in vitro investigation, including dynamic studies in flow-through cell apparatus and stress test device, forms the basis for the evaluation of nicotinic acid plasma concentrations in vivo. The occurrence of erratic, multiple NA plasma peaks after the administration of both extended-release products is a result of its local input excess over the metabolic threshold (at the level corresponding to maximum 2% of the administered dose, i.e., 20 mg of drug) due to the mechanical stresses of physiological intensity. We demonstrate how this behavior is similar for both marketed and test products. In this context, we describe how a robust ER matrix and well-designed formulation does not guarantee the test product's bioequivalence to the comparator one out of reasons unrelated to technology and biopharmaceutical properties, but because of the active compound's intrinsic pharmacokinetic characteristics, i.e., highly variable, extensive metabolism of nicotinic acid.


Assuntos
Niacina/química , Adulto , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Humanos , Niacina/administração & dosagem , Niacina/farmacocinética , Comprimidos/química , Equivalência Terapêutica
15.
AAPS PharmSciTech ; 21(3): 76, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970603

RESUMO

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1 week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1 week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3 weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.


Assuntos
Antibacterianos/uso terapêutico , Moxifloxacina/uso terapêutico , Nanopartículas , Periodontite/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Animais , Antibacterianos/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Géis , Moxifloxacina/química , Nanopartículas/química , Tamanho da Partícula , Periodontite/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Viscosidade
16.
ACS Appl Mater Interfaces ; 12(4): 4295-4307, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31904927

RESUMO

We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NPs) with negative, positive, and hydrophobic surfaces that were incorporated outside, inside, or between the lipid bilayers, respectively. To characterize how NPs are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NPs are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 °C with high enthalpy 34.8 J/g) avoiding the leakage of the encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100% of cellular uptake was achieved with a high cell survival (above 80%), which is preserved (83%) for doxorubicin-loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 h, leading to a cell survival reduction of 20%. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating to avoid drug degradation. In conclusion, these drug-loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place, efficiently using an external AMF to reduce or even eliminate side effects.


Assuntos
Antineoplásicos/química , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Liberação Controlada de Fármacos , Humanos , Campos Magnéticos , Nanopartículas/química
17.
Carbohydr Polym ; 231: 115714, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31888845

RESUMO

Although supramolecular prodrug self-assemblies have been proven as efficient nanocarriers for cancer therapy, tedious synthesis procedures have made their practical applications more difficult. In this paper, ß-cyclodextrin-based supramolecular self-assemblies (SSAs) were directly constructed by utilizing ß-cyclodextrin trimer (ß-CD3) as the host unit and unmodified curcumin as the guest unit. Due to the adjustment of host-guest inclusion and hydrophilic-hydrophobic interactions occurring in the SSAs, their morphology could be readily tuned by changing the ratio of the two components. Different self-assembly morphologies, such as spherical complex micelles, spindle-like complex micelles and multi-compartment vesicles, were obtained. Furthermore, basic cell experiments were performed to study the corresponding effects of the SSA shape on their biological properties. Compared to the other micelles, the spindle-like complex micelles exhibited enhanced cellular toxicity, uptake behaviors and apoptosis rates, and the spherical complex micelles exhibited poor performance. The performance of the multi-compartment vesicles was similar to that of the spindle-like complex micelles. The facile construction of these shape-regulated SSAs and their different cellular biological properties might be valuable in the controlled drug release field.


Assuntos
Curcumina/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , beta-Ciclodextrinas/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Humanos , Células MCF-7 , Micelas , Neoplasias , beta-Ciclodextrinas/farmacologia
18.
Mater Sci Eng C Mater Biol Appl ; 108: 110194, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923931

RESUMO

The thermal, physical, and morphological properties of diphenhydraminium ibuprofenate ([DIP][IBU]) adsorbed onto mesoporous silica (SiO2-60 Šand SiO2-90 Å) from solution were determined. The thermal, physical, and morphological properties of [DIP][IBU] supported on silica were determined. The adsorption of [DIP][IBU] on the pores and surface of silica was proven by N2 adsorption/desorption isotherms. Additionally, release profiles were determined for all systems, and the antinociceptive activity of neat [DIP][IBU] and [DIP][IBU] supported on silica were determined. The interaction of [DIP][IBU] and silica was dependent on pore size, with the formation of a [DIP][IBU] monolayer on SiO2-60 and a multilayer on SiO2-90. The release profile was sustained and slow and dependent on the pore size of the silica, in which the smaller the pore size, the faster the release. The nociceptive evaluation showed that [DIP][IBU] presents a greater (99.21 ±â€¯0.85%) antinociceptive effect than the ibuprofen (46 ±â€¯4.3%). Additionally, [DIP][IBU] on SiO2-60 (90 ±â€¯5.8%) had a greater antinociceptive effect than on SiO2-90 (73 ±â€¯13.2%), which indicates that in vivo tests are in accordance with the in vitro experiments.


Assuntos
Analgésicos , Ibuprofeno , Dor/tratamento farmacológico , Dióxido de Silício , Analgésicos/química , Analgésicos/farmacocinética , Analgésicos/farmacologia , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Avaliação Pré-Clínica de Medicamentos , Ibuprofeno/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/farmacologia , Masculino , Camundongos , Dor/metabolismo , Dor/fisiopatologia , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/farmacologia
19.
Mater Sci Eng C Mater Biol Appl ; 108: 110337, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923987

RESUMO

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO2) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO2 (spheres (S), rods (R). The dispersion of TiO2 was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO2 nanospheres (NOR@TiO2 (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO2 (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO2) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO2 nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.


Assuntos
Antineoplásicos , Nanocompostos , Neoplasias/tratamento farmacológico , Norfloxacino , Poliésteres , Titânio , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Células HCT116 , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Nanocompostos/química , Nanocompostos/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Norfloxacino/química , Norfloxacino/farmacocinética , Norfloxacino/farmacologia , Células PC-3 , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Titânio/química , Titânio/farmacocinética , Titânio/farmacologia
20.
Mater Sci Eng C Mater Biol Appl ; 108: 110191, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923988

RESUMO

Effective therapeutic delivery of peptide and protein drugs is challenged by short in vivo half-lives due to rapid degradation. Sustained release formulations of αCT1, a 25 amino acid peptide drug, would afford lower dosing frequency in indications that require long term treatment, such as chronic wounds and cancers. In this study, rhodamine B (RhB) was used as a model drug to develop and optimize a double emulsion-solvent evaporation method of poly(lactic-co-glycolic acid) (PLGA) nanoparticle synthesis. Encapsulation of αCT1 in these nanoparticles (NPs) resulted in a sustained in vitro release profile over three weeks, characterized by an initial burst release of approximately 50% of total encapsulated drug over the first three days followed by sustained release over the remaining two and a half weeks. NP uptake by glioblastoma stem cells was through endocytosis and RhB and αCT1 were observed in cells after at least 4 days.


Assuntos
Materiais Biomiméticos , Conexina 43 , Glioblastoma , Nanopartículas , Peptídeos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Linhagem Celular Tumoral , Conexina 43/química , Conexina 43/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Peptídeos/química , Peptídeos/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia
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