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1.
J Hazard Mater ; 416: 125861, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492809

RESUMO

Neonicotinoid insecticides have been widely used due to their excellent systemic activity and high insecticidal activity, but the problems of low utilization rate and environmental risk have attracted widespread attention. Controlled-release technology is an approach to realize the efficient utilization of pesticides and reduce environmental pressure. In this study, clothianidin (CLO) controlled-release granules (CLO@GR- TA (tannic acid)/Fe (III)) were prepared with TA/Fe (III) coordination chelate as the coating material. These granules exhibited the core-shell structure with 500-1200 µm of particle size, and had obvious release performance and hydrolysis behavior of coating materials. Pot experiments by root application showed that the CLO@GR-TA/Fe (III) showed balanced and lasting control efficacy to broad bean aphids. The plants have a stronger capacity for absorption and enrichment and a higher utilization rate of CLO for CLO@GR-TA/Fe (III), than those for 10% suspension concentrate (SC). One of the hydrolysates of coating materials, TA, a polyphenolic antioxidant, could improve the bioaccumulation amount and alleviating the oxidative stress response of CLO in plants. Our study illustrates that the controlled-release granules base on TA have efficient controlled-release properties and free radical scavenging performance that may eventually be used as pesticide carriers and antioxidants in the field of plant protection.


Assuntos
Praguicidas , Disponibilidade Biológica , Preparações de Ação Retardada , Guanidinas , Neonicotinoides/toxicidade , Estresse Oxidativo , Praguicidas/toxicidade , Tiazóis
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112271, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474830

RESUMO

Folic acid (FA) is a crucial vitamin for all living creatures. However, it is susceptible to degradation under pH, heat, ultraviolet (UV) and day sunlight conditions, resulting in lowering its bioavailability. Therefore, a versatile protective encapsulation system for FA is highly required to overcome its inherent instability. We report the use of the robust Lycopodium clavatum sporopollenin (LCS) microcapsules, extracted from their natural micrometer-sized raw spores, for FA microencapsulation. The physico-chemical characterisation of the LCS microcapsules are comprehensively investigated before and after the microencapsulation using SEM, elemental, CLSM, FTIR, TGA/DTG and XRD analyses, revealing a successful FA encapsulation within the LCS in an amorphous form. The phenylpropanoid acids, responsible for the UV protection and the autofluorescence of the LCS, were found in the LCS as evidenced by FTIR analysis. TGA/DTG results revealed that the hemi-cellulose and cellulose are the major component of the LCS. A controlled and sustained release of FA from FA-loaded LCS were achieved where the release profile of FA-loaded LCS was found to be pH-dependent. The percentages of cumulative FA released after 10 h at 37 ± 0.5 °C were 45.5% and 76.1% in pH 1.2 and 7.4, respectively, ensuring controlled and slow release in simulated physiological conditions. The FA release kinetic studies indicated the prevalence of the Fickian diffusion mechanism in pH 1.2, while anomalous non-Fickian transport was ascribed for FA release in pH 7.4. The in vitro cytotoxicity assay revealed that the obtained formulations were biocompatible against the human skin fibroblast (HSF) cell line. The versatile LCS microcapsules exhibited intriguing photostability for FA under UV or sunlight irradiation. Concretely, the obtained FA sustained delivery and photoprotection properties of these LCS microcapsules validate their multifunctional characteristics, opening up intriguing applications in oral and topical drug delivery as well as in food industry.


Assuntos
Ácido Fólico , Vitaminas , Biopolímeros , Cápsulas , Carotenoides , Preparações de Ação Retardada , Humanos , Cinética
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112273, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474832

RESUMO

To develop novel imprinted poly (methacrylic acid) nanoparticles for the controlled release of Rivastigmine Tartrate (RVS), the amalgamation of molecular imprinting techniques and polymerization of precipitates were applied in this work. By permuting different concentrations of pentaerythritol triacrylate (PETA) or trimethylolpropane triacrylate (TMPTA) as cross-linkers, ten different samples were synthesized, and their abilities assessed for RVS absorption. Among them, uniform mono-disperse nanoparticles were synthesized in an RVS/PMAA/PETA mole ratio of 1:6:12, named molecularly imprinted polymers 2 (MIP2), which showed the highest RVS absorption. Analytical procedures involving the Fourier transform infrared (FT-IR), Thermogeometric analysis (TGA), Field emission scanning electron microscopy (FE-SEM), Dynamic light scattering (DLS), and absorption/desorption porosimetry (BET) measurements were applied to characterize the morphology and physicochemical properties of the MIP2. In addition, the cytotoxicity of the MIP2 sample was measured by MTT assay on an L929 cell line. Studies pertaining to the in-vitro release of RVS from MIP2 samples showed that the prepared sample had a controlled and sustained release compared, which differed from the results obtained from the non-imprinted polymer (NIP) with the same formulization. Results obtained further reinforced the feasibility of prepared MIPs as a prime candidature for RVS drug delivery to alleviate Alzheimer's and other diseases.


Assuntos
Impressão Molecular , Polímeros Molecularmente Impressos , Adsorção , Preparações de Ação Retardada , Rivastigmina , Espectroscopia de Infravermelho com Transformada de Fourier , Tartaratos
4.
Biomater Sci ; 9(18): 6108-6115, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34369491

RESUMO

Nanomedicines have been widely used in the effective delivery of chemotherapeutic drugs due to their advantages such as increasing the half-life of drugs, selectively targeting tumor tissues, and thus reducing systemic toxicity. However, the low drug entrapment rate and the difficulty of real-controlled release at tumor sites hinder their further clinical translations. Here we have developed biodegradable polyionic micelles (PD-M) to facilitate black phosphorus (BP) encapsulation (PD-M@BP) for improved drug loading. With the introduction of BP, PTX-loaded PD-M@BP (PD-M@BP/PTX) with sizes of 124-162 nm exhibited superior encapsulation efficiency over 94% and excellent colloidal stability. Meanwhile, PD-M well protected BP from fast degradation to show the good photothermal performance under near-infrared (NIR) irradiation, thus achieving the remotely controlled fast PTX release due to micelle core melting and dissociation, accompanied by the synergistic photothermal tumor therapy. The in vivo results demonstrated that the PD-M@BP/PTX nanosystem not only realized significant inhibition of multi-drug resistant (MDR) cervical tumors (HeLa/PTXR tumor) by remote NIR-regulation, but also reduced the potential damage of chemotherapeutic drugs to the whole body, rendering these hybrid nanosystems as great tools to treat MDR tumors synergistically.


Assuntos
Micelas , Neoplasias , Preparações de Ação Retardada , Humanos , Nanomedicina , Fósforo
5.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443569

RESUMO

This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic-hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.


Assuntos
Tecnologia de Extrusão por Fusão a Quente , Resveratrol/química , Resveratrol/farmacocinética , Disponibilidade Biológica , Preparações de Ação Retardada , Portadores de Fármacos/química , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Polietilenoglicóis/química , Solubilidade
6.
Expert Opin Drug Metab Toxicol ; 17(9): 1149-1156, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34372746

RESUMO

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg). METHOD: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®. RESULTS: There were no significant differences in Cmax, AUC0-t and AUC0-48 between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate. CONCLUSION: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Leuprolida/administração & dosagem , Testosterona/sangue , Adulto , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Área Sob a Curva , Preparações de Ação Retardada , Humanos , Injeções , Leuprolida/farmacocinética , Leuprolida/farmacologia , Masculino , Microesferas , Método Simples-Cego , Fatores de Tempo , Adulto Jovem
7.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445521

RESUMO

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external stimuli such as temperature and pH as switches, these smart poly(aspartamide) derivatives can be used for convenient drug loading and controlled release. Here, we review the synthesis strategies for preparing these stimuli-responsive poly(aspartamide) derivatives and the latest developments in their applications as drug carriers.


Assuntos
Ácido Aspártico/análogos & derivados , Portadores de Fármacos/síntese química , Polímeros/síntese química , Ácido Aspártico/síntese química , Ácido Aspártico/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Polímeros/química , Temperatura
8.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34379922

RESUMO

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Assuntos
Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/administração & dosagem , Profilaxia Pré-Exposição , Piridonas/administração & dosagem , Tenofovir/uso terapêutico , Administração Oral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos/genética , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Homossexualidade Masculina , Humanos , Injeções Intramusculares/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Pessoas Transgênero , Adulto Jovem
9.
ACS Appl Mater Interfaces ; 13(33): 39066-39075, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387079

RESUMO

A controlled release formulation based on silica microcapsules is an ideal selection to improve both the effective utilization and duration of pesticides to decrease ecological damage. Herein, a simple and green method for preparing double-shelled microcapsules was developed using a newly prepared quaternary ammonium ionic liquid (IL) as the functional additive to entrap avermectin (Ave) in mesoporous silica nanospheres (MSNs) and tannic acid-Cu (TA-Cu) complex as the sealing agent to form the core-shell structure (Ave-IL@MSN@TA-Cu). The obtained microcapsules with an average size of 538 nm had pH-responsive release property and good stability in soil. The half-life of microcapsules (34.66 days) was 3 times that of Ave emulsifiable concentrate (EC) (11.55 days) in a test soil, which illustrated that microcapsules could protect Ave from rapid degradation by microorganisms by releasing TA, copper, and quaternary ammonium in the soil. Ave-IL@MSN@TA-Cu microcapsules had better nematicidal activity and antibacterial activity than Ave EC due to the synergistic effect of Ave, IL, and copper incorporated in the microcapsules. Pot experiments showed that the control efficacy of microcapsules was 87.10% against Meloidogyne incognita, which is better than that of Ave EC (41.94%) at the concentration of 1.0 mg/plant by the root-irrigation method after 60 days of treatment owing to the extended duration of Ave in microcapsules. The simple and green method for the preparation of double-shelled microcapsules based on natural quaternary ammonium IL would have tremendous potential for the extensive development of controlled release pesticide formulations.


Assuntos
Cápsulas/química , Preparações de Ação Retardada/química , Controle de Pragas/métodos , Praguicidas/química , Dióxido de Silício/química , Tylenchoidea/efeitos dos fármacos , Animais , Complexos de Coordenação/química , Cobre/química , Preparações de Ação Retardada/farmacologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Química Verde , Concentração de Íons de Hidrogênio , Líquidos Iônicos/química , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/farmacologia , Praguicidas/farmacologia , Porosidade , Compostos de Amônio Quaternário/química , Solubilidade , Taninos/química , Fatores de Tempo
10.
Ned Tijdschr Geneeskd ; 1652021 05 25.
Artigo em Holandês | MEDLINE | ID: mdl-34346606

RESUMO

BACKGROUND: Medicines with controlled release can cause a rare phenomenon, known as pharmacobezoar, following overdose of these medications. CASE DESCRIPTION: A case of a 56-year-old women with severe clomipramine intoxication is described. X-ray of the abdomen showed a cluster of tablets in the caecum. Lab results showed severe plasma concentration of clomipramine. Patient was treated with active coal and remained stable. CONCLUSION: It is important to be aware of the presence of pharmacobezoar in intoxication with controlled release medicines. The formation of pharmacobezoar can lead to unpredictable duration of intoxication.


Assuntos
Bezoares , Overdose de Drogas , Bezoares/induzido quimicamente , Clomipramina , Preparações de Ação Retardada , Feminino , Humanos , Pessoa de Meia-Idade , Estômago
11.
Georgian Med News ; (314): 172-179, 2021 May.
Artigo em Russo | MEDLINE | ID: mdl-34248050

RESUMO

According to the WHO data, over 35 million people in the world suffer from severe forms of cognitive impairment. Due to the insufficient effectiveness of separate therapy for amyloid or vascular pathologies, an opinion is expressed about the prospects of combined pharmacotherapy of cognitive impairments. The aim of the study was the pharmaceutical development of the combined tablet dosage form formulation with modified release of citicoline and memantine for the treatment of cognitive impairments. Information bases (eLibrary, PubMed) were used, content analysis on State Register of Medicinal Remedies database (grls.rosminzdrav.ru). The compatibility assessment was carried out by stress experiments method in combination with chromatographic analysis. Comparative pharmacokinetic studies were carried out on rabbits. The justification of the pharmacological and clinical feasibility of the proposed fixed dose combination has been carried out, the objective advantage of which is the potentiation of the pharmacotherapeutic action due to the unidirectional effect of memantine and citicoline, and the expected effect is to improve cognition, functioning and behavior and / or slow down their deterioration. The use of the combination will allow achieving ease of treatment, reducing costs, and, accordingly, compliance. The choice of the optimal dosage form for the developed combination was carried out: a tablet containing two release methods: memantine - immediate release, citicoline - prolonged release. The compatibility of the pharmaceutical substances memantine hydrochloride and citicoline monosodium salt with each other and the excipients planned for use in the formulation has been experimentally revealed. Comparative pharmacokinetic studies of the developed combined drug have been carried out.


Assuntos
Excipientes , Memantina , Animais , Preparações de Ação Retardada , Desenvolvimento de Medicamentos , Coelhos , Comprimidos
12.
Anal Chem ; 93(30): 10712-10718, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34283578

RESUMO

Herein, a split-type immunoassay strategy instigated by cation exchange (CE) and changing the capacity of an electron donor in an electrolyte solution is optimized, namely, for differentiating the biological-specific binding assay and photoelectrochemical (PEC) analysis. MoSe2/CdSe, a Z-scheme heterojunction with efficient visible light absorption and a low recombination of carriers, is used as a photoelectrode substrate. Silver ions (Ag+) as the initiator of CE are generated by the acidolysis of evenly loaded silver nanoparticles on mesoporous silica nanospheres (MSNs). The theoretical calculation and experimental results confirm that Ag+ replaces Cd2+ in CdSe and retains the crystal structure of MoSe2. However, this behavior destroys the perfectly matched heterojunction structure and introduces defects, which led to the reduction of the photocurrent response. In addition, ascorbate oxidase in combination with MSNs can be used as a consumptive agent of the electron donor, which further improves the sensitivity and reliability of the sensor. As a proof of principle, neuron-specific enolase was applied to elucidate the potential application of the PEC immunoassay in clinical diagnosis, and the obtained linear range of the sensor was from 0.0001 to 100 ng/mL with a detection limit of 28 fg/mL (S/N = 3).


Assuntos
Técnicas Biossensoriais , Compostos de Cádmio , Nanopartículas Metálicas , Compostos de Selênio , Cátions , Preparações de Ação Retardada , Técnicas Eletroquímicas , Humanos , Imunoensaio , Limite de Detecção , Reprodutibilidade dos Testes , Prata
14.
Mater Sci Eng C Mater Biol Appl ; 127: 112210, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225862

RESUMO

Thymopentin (TP5) is widely used in the treatment of autoimmune diseases, but the short in vivo half-life of TP5 strongly restricts its clinical applications. A series of blank and TP5 loaded hydrogels were synthesized via reversible dual imine bonding by mixing water soluble O-carboxymethyl chitosan (CMCS) with a dynamer (Dy) prepared from Jeffamine and benzene-1,3,5-tricarbaldehyde. TP5 release from hydrogels was studied at 37 °C under in vitro conditions. The molar mass of CMCS, drug loading conditions and drug content were varied to elucidate their effects on hydrogel properties and drug release behaviors. Density functional theory was applied to theoretically confirm the chemical connections between TP5 or CMCS with Dy. All hydrogels exhibited interpenetrating porous architecture with average pore size from 59 to 83 µm, and pH-sensitive swelling up to 10,000% at pH 8. TP5 encapsulation affected the rheological properties of hydrogels as TP5 was partially attached to the network via imine bonding. Higher TP5 loading led to higher release rates. Faster release was observed at pH 5.5 than at pH 7.4 due to lower stability of imine bonds in acidic media. Fitting of release data using Higuchi model showed that initial TP5 release was essentially diffusion controlled. All these findings proved that the dynamic hydrogels are promising carriers for controlled delivery of hydrophilic drugs, and shed new light on the design of drug release systems by both physical mixing and reversible covalent bonding.


Assuntos
Quitosana , Timopentina , Aldeídos , Preparações de Ação Retardada , Portadores de Fármacos , Hidrogéis , Concentração de Íons de Hidrogênio , Iminas
15.
Mater Sci Eng C Mater Biol Appl ; 127: 112226, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225871

RESUMO

In this work, we introduce, for the first time, novel hybrid microneedle patches with implantable poly(lactic-co-glycolic acid) (PLGA) tips aligned with hydrogel-forming microneedle bases (HFMB) using a dissolvable material. A model dye, Nile red, and an antifungal drug, amphotericin B, were loaded into the PLGA tips in a controlled manner by multiple castings. Three different types of pre-formed microneedle bases including conventional dissolving baseplates (MN0), HFMB with needle heights of 600 µm (MN6) and HFMB with needle heights of 800 µm (MN8) were investigated. Compared to the conventional dissolving baseplate (MN0)-based PLGA tipped implantable microneedle design, the addition of the pre-formed HFMB (MN8) improved in vitro and ex vivo insertion capacities of the patches, increased ex vivo drug delivery efficiency up to 80% of the loaded drug and speeded up the implantation process to within 1 min. An adhesion test indicated that the hydrogel baseplate used in this study was easier to peel off from the skin than the dissolving baseplate. In vitro release studies demonstrated that the release of amphotericin B from the drug loading PLGA tips lasts for a week. Antifungal tests of the inserted amphotericin B loaded PLGA tips revealed their antifungal effects against Candida albicans. The MN8 did not dissolve, leaving no viscous residue but absorbed water and disintegrated after immersion into water. The hybrid PLGA-tipped microneedle system will be ideal for rapid implantation and sustained release of amphotericin B for dermal fungal infections. This hybrid patch design is a novel promising technology for delivering drug-eluting microimplants into the skin while ensuring easy and complete removal of the HFMB. It could have many potential applications in implantable intradermal drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Administração Cutânea , Preparações de Ação Retardada , Agulhas , Pele
16.
Int J Pharm ; 605: 120838, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34197909

RESUMO

A fixed dose combination (FDC) bilayer tablet, consisting of high-dose metformin HCl in a sustained release layer and low-dose evogliptin tartrate in an immediate release layer, was developed based on a quality by design (QbD) approach. To implement QbD approach, the bilayer tableting process parameters judged as high risk through risk analysis were optimized by a central composite face-centered design as a design of experiment (DOE) methodology. Using DOE, the optimized conditions of the tableting process for drug products that satisfy the established quality target product profiles were obtained. The content uniformity of low-dose evogliptin tartrate in the optimized bilayer tablet prepared on a large scale was confirmed by at-line transmittance Raman spectroscopy as a process analytical technology. In addition, the in vitro drug release and in vivo pharmacokinetic studies showed that metformin HCl and evogliptin tartrate in the bilayer tablet is bioequivalent to those of the respective reference drugs. Furthermore, the physicochemical stability of the optimized bilayer tablet during storage under long-term and accelerated conditions was also confirmed. Therefore, it can be concluded that the QbD approach is an effective way to develop a new FDC bilayer tablet that is easy to scale up for successful commercialization.


Assuntos
Metformina , Preparações de Ação Retardada , Combinação de Medicamentos , Liberação Controlada de Fármacos , Comprimidos
17.
J Nanosci Nanotechnol ; 21(12): 5867-5880, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229781

RESUMO

The usefulness of carboxymethyl cellulose (CMC) as a matrix material in enhancing the controlled release formulations of bispyribac (BP) herbicide from the interlayer gallery of zinc hydroxide nitratesodium dodecylsulphate-bispyribac (ZHN-SDS-BP) nanocomposite was investigated. The CMC coated nanocomposite, ZHN-SDS-BP-CMC was characterised using several instruments for the determination of its physicochemical properties. The release rates of the BP were measured using a UV spectrophotometer, and the aqueous solutions containing PO3-4 , SO2-4 and Cl- were selected as release media in the release studies so as to mimic the real conditions of environmental soil. Significant release time delays, triggered by the gelation forming ability and hygroscopic nature of CMC, were observed in all release media, and the release processes were found to behave in a concentration-dependent manner in all release media. Fitting the release data into several kinetic models demonstrated that release in aqueous solutions of Na3PO4 and Na2SO4 was governed by pseudo second order processes, whereas the release in an aqueous NaCl solution was governed by the parabolic diffusion kinetic model. The potential of CMC in prolonging the release of BP from ZHN-SDS-BP-CMC can potentially help in reducing the pollution resulting from the overuse of pesticides.


Assuntos
Herbicidas , Nanocompostos , Benzoatos , Carboximetilcelulose Sódica , Preparações de Ação Retardada , Hidrogéis , Hidróxidos , Nitratos , Pirimidinas , Sódio
18.
ACS Appl Mater Interfaces ; 13(27): 32295-32306, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34196538

RESUMO

Synthetic fungicides have been widely used to protect crops from fungal diseases. However, excessive use of synthetic fungicides leads to the generation of fungicide resistance in fungal pathogens. Recently, smart cargo delivery systems have been introduced for the construction of a pesticide delivery nanoplatform, benefiting from their controlled release performance. Herein, a fungal pathogen microenvironment-responsive supramolecular fungicide nanoplatform has been designed and constructed, using quaternary ammonium salt (Q)-modified mesoporous silica nanoparticles (MSN-Q NPs) as nanocarriers loaded with berberine hydrochloride (BH) and carboxylatopillar[5]arene (CP[5]A) as nanogates to form BH-loaded CP[5]A@MSN-Q NPs for effective inhibition of Botrytis cinerea. CP[5]A as nanogates can endow the fungicide nanoplatform with pH stimuli-responsive release features for the control of fungicide release. The loaded BH, as a natural plant fungicide, provides an ecofriendly alternative to synthetic fungicides for controlling B. cinerea. Interestingly, we use oxalic acid (OA) secreted by B. cinerea as a trigger so that BH can be released from the fungicide nanoplatform on demand under pathogen microenvironments for controlling B. cinerea. The experimental results indicate that the fabricated fungicide nanoplatform could effectively inhibit the mycelial growth and spore germination, providing a new way for the management of B. cinerea in actual application.


Assuntos
Portadores de Fármacos/química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Berberina/química , Berberina/farmacologia , Botrytis/efeitos dos fármacos , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Porosidade , Compostos de Amônio Quaternário/química
19.
ACS Appl Mater Interfaces ; 13(27): 31379-31392, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34197081

RESUMO

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 µm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (µPLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only ∼20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-µPLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-µPL (1 mg kg-1) decreased the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-µPL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the µPLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.


Assuntos
Cartilagem Articular/metabolismo , Dexametasona/química , Dexametasona/metabolismo , Portadores de Fármacos/química , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Animais , Biomarcadores/metabolismo , Preparações de Ação Retardada , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intra-Articulares , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estresse Mecânico
20.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200896

RESUMO

The goals of this study are to develop a high purity patented silk fibroin (SF) film and test its suitability to be used as a slow-release delivery for insulin-like growth factor-1 (IGF-1). The release rate of the SF film delivering IGF-1 followed zero-order kinetics as determined via the Ritger and Peppas equation. The release rate constant was identified as 0.11, 0.23, and 0.09% h-1 at 37 °C for SF films loaded with 0.65, 6.5, and 65 pmol IGF-1, respectively. More importantly, the IGF-1 activity was preserved for more than 30 days when complexed with the SF film. We show that the IGF-1-loaded SF films significantly accelerated wound healing in vitro (BALB/3T3) and in vivo (diabetic mice), compared with wounds treated with free IGF-1 and an IGF-1-loaded hydrocolloid dressing. This was evidenced by a six-fold increase in the granulation tissue area in the IGF-1-loaded SF film treatment group compared to that of the PBS control group. Western blotting analysis also demonstrated that IGF-1 receptor (IGF1R) phosphorylation in diabetic wounds increased more significantly in the IGF-1-loaded SF films group than in other experimental groups. Our results suggest that IGF-1 sustained release from SF films promotes wound healing through continuously activating the IGF1R pathway, leading to the enhancement of both wound re-epithelialization and granulation tissue formation in diabetic mice. Collectively, these data indicate that SF films have considerable potential to be used as a wound dressing material for long-term IGF-1 delivery for diabetic wound therapy.


Assuntos
Bombyx/química , Diabetes Mellitus Experimental/fisiopatologia , Sistemas de Liberação de Medicamentos , Fibroblastos/efeitos dos fármacos , Fibroínas/química , Fator de Crescimento Insulin-Like I/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Preparações de Ação Retardada , Feminino , Fator de Crescimento Insulin-Like I/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Reepitelização , Receptores para Leptina/fisiologia
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