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1.
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
2.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200350

RESUMO

A considerable interest in cancer research is represented by the development of magnetic nanoparticles based on biofunctionalized polymers for controlled-release systems of hydrophobic chemotherapeutic drugs targeted only to the tumor sites, without affecting normal cells. The objective of the paper is to present the synthesis and in vitro evaluation of the nanocomposites that include a magnetic core able to direct the systems to the target, a polymeric surface shell that provides stabilization and multi-functionality, a chemotherapeutic agent, Paclitaxel (PTX), and a biotin tumor recognition layer. To our best knowledge, there are no studies concerning development of magnetic nanoparticles obtained by partial oxidation, based on biotinylated N-palmitoyl chitosan loaded with PTX. The structure, external morphology, size distribution, colloidal and magnetic properties analyses confirmed the formation of well-defined crystalline magnetite conjugates, with broad distribution, relatively high saturation magnetization and irregular shape. Even if the ability of the nanoparticles to release the drug in 72 h was demonstrated, further complex in vitro and in vivo studies will be performed in order to validate the magnetic nanoparticles as PTX delivery system.


Assuntos
Antineoplásicos Fitogênicos/química , Biotina/química , Quitosana/análogos & derivados , Nanopartículas de Magnetita/química , Paclitaxel/química , Linhagem Celular Tumoral , Quitosana/química , Coloides/química , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Células MCF-7 , Polímeros/química
3.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200887

RESUMO

Royal jelly is a natural substance produced by worker bees that possesses a variety of biological activities, including antioxidant, anti-inflammatory, antibacterial, and protective. Although fresh royal jelly is kept at low temperatures, to increase its stability, it needs to be incorporated into pharmaceutical formulations, such as in situ gels. The aim of this study was to formulate in situ ocular gels containing Lithuanian royal jelly for topical corneal use in order to increase the retention time of the formulation on the ocular surface and bioavailability. Gels were evaluated for physicochemical characteristics (pH, rheological properties, refractive index) and in vitro drug release measuring the amount of 10-hydroxy-2-decenoic acid (10-HDA). An ocular irritation test and cell viability tests were performed using the SIRC (Statens Seruminstitut Rabbit Cornea) cell culture line. Results indicated that all the in situ gels were within an acceptable pH and refractive index range close to corneal properties. Rheology studies have shown that the gelation temperature varies between 25 and 32 °C, depending on the amount of poloxamers. The release studies have shown that the release of 10-HDA from in situ gels is more sustained than royal jelly suspension. All gel formulations were non-irritant according to the short-time exposure test (STE) using the SIRC cell culture line, and long-term cell viability studies indicated that the formulations used in small concentrations did not induce cell death. Prepared in situ gels containing royal jelly have potential for ocular drug delivery, and they may improve the bioavailability, stability of royal jelly, and formation of non-irritant ocular formulations.


Assuntos
Córnea/efeitos dos fármacos , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Géis/química , Géis/farmacologia , Animais , Abelhas/metabolismo , Disponibilidade Biológica , Produtos Biológicos/química , Produtos Biológicos/farmacocinética , Produtos Biológicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos , Córnea/metabolismo , Ácidos Decanoicos/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Excipientes/química , Géis/farmacocinética , Poloxâmero/química , Coelhos , Reologia , Temperatura
4.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200922

RESUMO

The use of paper as a sustainable packaging material is favored, but it lacks sufficient barrier properties in terms of water repellence and oil resistance. Novel approaches consider active packaging materials or coatings with controlled release providing additional functionality for delivery of specific components to the surface. In this study, the development of a waterborne coating with organic nanoparticles and encapsulated sunflower oils is presented as a system for thermal release of the oil and on-demand tuning of the final barrier properties of the paper substrate. After synthesis of the nanoparticles, it seems that the encapsulation of various grades of sunflower oil (i.e., either poly-unsaturated or mono-unsaturated) strongly affects the encapsulation efficiency and thermal release profiles. The water contact angles are controlled by the oil release and chemical surface composition of the coating upon thermal heating. The oil resistance of the paper improves as a more continuous oil film is formed during thermal release. In particular, the chemical surface composition of the paper coatings is detailed by means of micro-Raman spectroscopy and surface imaging, which provide an analytical quantification tool to evaluate surface coverage, oil delivery, and variations in organic coating moieties.


Assuntos
Preparações de Ação Retardada/química , Óleo de Girassol/química , Embalagem de Alimentos/métodos , Nanopartículas/química , Papel , Água/química
5.
Int J Mol Sci ; 22(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299020

RESUMO

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Polímeros/química , Engenharia Tecidual/métodos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Materiais Biocompatíveis/química , Preparações de Ação Retardada/química , Técnicas de Transferência de Genes , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Íons/química , Ligantes , Temperatura
6.
Molecules ; 26(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203117

RESUMO

Three phosphate glass compositions, VF1, VF2, and VF3, containing macro and micronutrients with different [K2O/(CaO+MgO)] ratio, were formulated to be used as controlled release fertilizers for tomato crop, depending on their chemical durability in water and their propriety with respect to the standards of controlled-release fertilizers. This study investigated the influence of [K2O/(CaO+MgO)] ratio variation on glass properties. For this, the elaborated glasses have undergone a chemical characterization using inductively coupled plasma atomic emission spectroscopy, a thermal characterization using differential thermal analysis, a physicochemical characterization based on density and molar volume measurements, and a structural characterization using Raman spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. In addition, the chemical durability was determined by measuring the percentage of weight loss and the pH. Results revealed that the glass structure and composition have the mean role in controlling the release of nutrients in water. By increasing [K2O/(CaO+MgO)] ratio, the dissolution rates of the glasses increased due to the shrinking in the rate of crosslinking between phosphate chains, accompanied with a diminution in transition and crystallization temperatures, and an increase in the molar volume. An agronomic valorization of VF1 and VF2 glass fertilizers, which showed dissolution profiles adequate to the criteria of controlled-release fertilizers, was carried out to evaluate their efficiency on tomato crops. These glass fertilizers improved soil mineral content and tomato performances in comparison to the control and NPK treatments with the distinction of VF2. The results highlight the effectiveness of these smart fertilizers toward their potential large-scale application to improve crop production and quality for high nutritional value foods.


Assuntos
Produção Agrícola , Produtos Agrícolas/crescimento & desenvolvimento , Fertilizantes , Frutas/crescimento & desenvolvimento , Vidro/química , Lycopersicon esculentum/crescimento & desenvolvimento , Fosfatos , Solo , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Fosfatos/química , Fosfatos/farmacologia
7.
AAPS PharmSciTech ; 22(5): 188, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34159427

RESUMO

Omeprazole is a widely used over-the-counter (20 mg) proton pump inhibitor, usually supplied as oral enteric-coated pellets intended to release at pH 5.5 and higher; however, it is sensitive to acidic pH. The likelihood of elevated gastric pH in practice is very high for patients; thus, the aim of this study was to investigate the effect of elevated pH on the performance of commercial omeprazole pellets. Commercial enteric-coated delayed-release pellets were tested with water uptake-weight loss (WU-WL) test at pH range between 1.2 and 4.5 in addition to "gastric" (pH 1.2 or 4.5) and "intestinal" (pH 7.4) phase dissolution tests. The range of physical characteristics of pellets was determined with a single pellet size and sedimentation time measurement, followed by the application of modified Stokes' Law equation. The coefficient of variation of pellet size and density, and volume-density determination coefficient (R2) as descriptors of coating thickness and microstructure variability, degree of ionisation of enteric polymers, aqueous solubility and molecular weight of plasticisers have been found useful to explain commercial delayed-release pellets behaviour during WU-WL and dissolution test. Investigated commercial delayed-release pellets demonstrated pH-dependent WU-WL results. "Gastric phase" dissolution testing of pellets at pH 4.5 showed the highest omeprazole degradation (48.1%) for Nosch Labs, intermediate values of dose loss (23.4% and 17.1%) for Teva and UQUIFA delayed-release pellets, respectively. Lab Liconsa pellets have been found as the least susceptible (3.2% of dose loss). Additionally, "gastric phase" dissolution test at pH 4.5 significantly influenced omeprazole release during the "intestinal phase". The risk of inadequate therapy associated with intake of investigated enteric-coated delayed-release pellets at elevated gastric pH has been found as minimal for Lab Liconsa and has increased from UQUIFA and Teva to Nosh Labs pellets.


Assuntos
Medicamentos Genéricos/química , Absorção Gastrointestinal/efeitos dos fármacos , Omeprazol/química , Patentes como Assunto , Inibidores da Bomba de Prótons/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Medicamentos Genéricos/farmacocinética , Absorção Gastrointestinal/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Omeprazol/farmacocinética , Inibidores da Bomba de Prótons/farmacocinética , Solubilidade , Comprimidos com Revestimento Entérico , Adulto Jovem
8.
AAPS PharmSciTech ; 22(5): 170, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34085150

RESUMO

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.


Assuntos
Resinas Acrílicas/química , Administração Oftálmica , Quitosana/química , Nanofibras/química , Ofloxacino/química , Álcool de Polivinil/química , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/farmacocinética , Animais , Antibacterianos/química , Química Farmacêutica/métodos , Quitosana/administração & dosagem , Quitosana/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Nanofibras/administração & dosagem , Ofloxacino/administração & dosagem , Ofloxacino/farmacocinética , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/farmacocinética , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
9.
Clin Drug Investig ; 41(7): 639-645, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34110614

RESUMO

BACKGROUND AND OBJECTIVE: Omecamtiv mecarbil (OM) is a cardiac myosin activator under clinical development for the treatment of heart failure. Two modified-release (MR) novel OM minitablet formulations were developed to support the planned investigation of chronic heart failure in pediatric patients. The primary objective of this study was to determine the bioavailability of the minitablets relative to the adult matrix MR formulation tablets. METHODS: In a randomized, 5-period, crossover study, 20 healthy subjects received each of the following treatments orally: one 25-mg adult matrix MR tablet, 25 1-mg slow-release minitablets, 25 1-mg fast-release minitablets, six 1-mg slow-release minitablets, or six 1-mg fast-release minitablets after an overnight fast of at least 10 h with a minimum washout of 7 days between treatments. Blood samples were collected for up to 168 h. OM pharmacokinetic parameters were estimated using non-compartmental methods. RESULTS: When OM was administered as 25 1-mg OM slow-release minitablets, AUClast, AUCinf, and Cmax were 0.998-, 1.00-, and 1.29-fold of a single 25-mg OM matrix MR tablet, respectively. When OM was administered as 25 1-mg OM fast-release minitablets, AUClast, AUCinf, and Cmax were 1.26-, 1.25-, and 2.21-fold of a single 25-mg OM matrix MR tablet, respectively. The slow- and fast-release minitablets display approximately dose-proportional pharmacokinetics. There were no serious adverse events or treatment-emergent adverse events leading to discontinuation from the study. CONCLUSIONS: Relative bioavailability of slow-release minitablets was demonstrated to be similar to the adult matrix MR formulation.


Assuntos
Preparações de Ação Retardada/química , Comprimidos/química , Ureia/análogos & derivados , Administração Oral , Adolescente , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Composição de Medicamentos , Feminino , Meia-Vida , Voluntários Saudáveis , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/etiologia , Ureia/efeitos adversos , Ureia/sangue , Ureia/farmacocinética , Ureia/uso terapêutico , Adulto Jovem
10.
Acta Biochim Biophys Sin (Shanghai) ; 53(8): 1027-1036, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34109980

RESUMO

Targeted delivery and smart response of nanomedicine hold great promise for improving the therapeutic efficacy and alleviating the side effects of chemotherapy agents in cancer treatment. However, availability of only a few studies that discuss organic nanomedicines with these properties limits the development prospects of nanomedicines. In the present study, folic acid (FA)-targeted delivery and glutathione (GSH) smart responsive nanomedicine were rationally designed for paclitaxel (PTX) delivery for the treatment of lung cancer. Compared with other stimuli-responsive nanomedicines, this nanocarrier was not only sensitive to biologically relevant GSH for on-demand drug release but also biodegradable into biocompatible products after fulfilling its delivery task. The nanomedicine first entered tumor cells via FA and its receptor-mediated endocytosis. After the lysosomal escape, poly(lactic-co-glycolic acid) (PLGA) nanomedicine was triggered by a higher level of GSH and released its cargo into the tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells significantly but also possessed less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the potential of a multifunctional nano-platform to enhance bioavailability and reduce the side effects of chemotherapy agents.


Assuntos
Carcinoma Pulmonar de Lewis , Ácido Fólico , Glutationa/metabolismo , Neoplasias Pulmonares , Nanomedicina , Paclitaxel , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia
11.
ACS Appl Mater Interfaces ; 13(25): 29231-29246, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34137251

RESUMO

With the increasing volume of cardiovascular surgeries and the rising adoption rate of new methodologies that serve as a bridge to cardiac transplantation and that require multiple surgical interventions, the formation of postoperative intrapericardial adhesions has become a challenging problem that limits future surgical procedures, causes serious complications, and increases medical costs. To prevent this pathology, we developed a nanotechnology-based self-healing drug delivery hydrogel barrier composed of silicate nanodisks and polyethylene glycol with the ability to coat the epicardial surface of the heart without friction and locally deliver dexamethasone, an anti-inflammatory drug. After the fabrication of the hydrogel, mechanical characterization and responses to shear, strain, and recovery were analyzed, confirming its shear-thinning and self-healing properties. This behavior allowed its facile injection (5.75 ± 0.15 to 22.01 ± 0.95 N) and subsequent mechanical recovery. The encapsulation of dexamethasone within the hydrogel system was confirmed by 1H NMR, and controlled release for 5 days was observed. In vitro, limited cellular adhesion to the hydrogel surface was achieved, and its anti-inflammatory properties were confirmed, as downregulation of ICAM-1 and VCAM-1 was observed in TNF-α activated endothelial cells. In vivo, 1 week after administration of the hydrogel to a rabbit model of intrapericardial injury, superior efficacy was observed when compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune infiltration of CD3+ lymphocytes and CD68+ macrophages, as well as NF-κß downregulation. We presented a novel nanostructured drug delivery hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after a surgical intervention.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , Nanoestruturas , Pericárdio/cirurgia , Aderências Teciduais/prevenção & controle , Animais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Modelos Animais de Doenças , Hidrogéis/química , Hidrogéis/farmacologia , Masculino , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Coelhos
12.
Molecules ; 26(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063753

RESUMO

Azobenzenes are photochromic molecules that possess a large range of applications. Their syntheses are usually simple and fast, and their purifications can be easy to perform. Oligosaccharide is also a wide family of biopolymer constituted of linear chain of saccharides. It can be extracted from biomass, as for cellulose, being the principal constituent of plant cell wall, or it can be enzymatically produced as for cyclodextrins, having properties not far from cellulose. Combining these two materials families can afford interesting applications such as controlled drug-release systems, photochromic liquid crystals, photoresponsive films or even fluorescent indicators. This review will compile the different syntheses of azo-dyes-grafted oligosaccharides, and will show their various applications.


Assuntos
Compostos Azo/química , Oligossacarídeos/síntese química , Celulose/química , Preparações de Ação Retardada/química , Corantes Fluorescentes/química , Cristais Líquidos/química , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação
13.
Int J Biol Macromol ; 182: 1582-1589, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019926

RESUMO

Nano-fiber composites have shown promising potential in biomedical and biotechnological applications. Herein, novel nano-fiber composites constituting a blend of polyvinyl alcohol (PVA) and chitosan (CS) along with different weight ratios of nano-bioactive glass (BG) were prepared by electrospinning. Nano-fibers incorporating 10% (by wt.) of BG were uniform, dense and defect-free with a diameter of 20-125 nm. The model osteoporotic drug (Risedronate sodium) was blended with the electrospinning forming solution and the in-vitro drug release was further studied. About 30% of the drug was released after only 30 min and the release pattern was sustained over 96 h. Drug release took place through a two-stage intra-particle diffusion mechanism. BG-incorporated nano-fibers markedly retarded the drug release profile relative to their BG-free counterparts. They also enhanced the drug release efficiency by releasing 93 ± 4% of the drug. The developed nano-fiber composites can be potentially used as drug-delivery vehicles due to their efficiency and sustained drug release capacity.


Assuntos
Quitosana/química , Nanocompostos/química , Álcool de Polivinil/química , Preparações de Ação Retardada/química , Vidro/química
14.
Nanotheranostics ; 5(4): 417-430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33972918

RESUMO

Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify nanoprobe uptake into cells. Second, Balb/c mice were co-dosed with NRPV and EuS or lutetium177-doped EuS (177LuEuS) theranostic nanoparticles to assess NRPV biodistribution via mass spectrometry. Third, single photon emission computed tomography (SPECT-CT) and magnetic resonance imaging (MRI) bioimaging were used to determine nanotheranostic and NRPV anatomic redistribution over time. Results: EuS nanoprobes and NRPV entered cells through dynamin-dependent pathways. SPECT-CT and MRI identified biodistribution patterns within the reticuloendothelial system for EuS that was coordinate with NRPV trafficking. Conclusions: EuS nanoprobes parallel the uptake and biodistribution of NRPV. These data support their use in modeling NRPV delivery to improve treatment strategies.


Assuntos
Fármacos Anti-HIV , Portadores de Fármacos , Európio , Infecções por HIV , HIV-1/metabolismo , Imageamento por Ressonância Magnética , Nanopartículas , Rilpivirina , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Sulfetos , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Európio/química , Európio/farmacocinética , Európio/farmacologia , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Rilpivirina/química , Rilpivirina/farmacocinética , Rilpivirina/farmacologia , Sulfetos/química , Sulfetos/farmacocinética , Sulfetos/farmacologia
15.
Int J Biol Macromol ; 182: 1769-1784, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34051259

RESUMO

This work attempts to resolve one of the key issues related to the design and development of sustained-release spherule of aspirin for oral formulations, tailored to treat COVID-19. For that, in the Design of Experiments (DOE) an arbitrary interface, "coating efficiency" (CE) is introduced and scaled the cumulative percentage coating (CPC) to get predictable control over drug release (DR). Subsequently, the granules containing ASP are converted to spherules and then to Ethyl cellulose (EC) Coated spherules (CS) by a novel bed coating during the rolling (BCDR) process. Among spherules, one with 0.35 mm than 0.71 mm shows required properties. The CS has a low 1200 angle by Optical Microscopy (OM), smooth surface without cracks by scanning electron microscopy (SEM), and better flow properties (Angle of repose 29.69 ± 0.780, Carr's index 6.73 ± 2.24%, Hausner's Ratio 1.07 ± 0.03) than granules and spherules. Once certain structure-dependent control over release is attained (EC coated spherules shows 10% reduction in burst release (BR) than uncoated spherules showing a release of 80-91%) the predictability is achieved and Design of space (DOS) by DOE (CE-70.14%and CPC-200% and DR-61.54%) is established. The results of DOE to experimentally validated results were within 20% deviation. The aspirin is changing its crystal structure by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) from Form-I to Form-II showing polymorphism inside the drug reservoir with respect to the process. This CE and CPC approach in DOE can be used for delivery system design of other labile drugs similar to aspirin in emergency situations.


Assuntos
Aspirina , COVID-19/tratamento farmacológico , Celulose/análogos & derivados , SARS-CoV-2 , Aspirina/química , Aspirina/farmacocinética , Celulose/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos
16.
AAPS PharmSciTech ; 22(5): 165, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34046797

RESUMO

In the present study, different in situ hydrogel formulations of docetaxel (DTX) based on biocompatible polymers such as Hyaluronic Acid (HA), poloxamer-407, chitosan and gellan gum were formulated to increase its therapeutic efficacy and reduce toxicity. DTX was loaded in nanovesicles (20 mg/mL equivalent to commercial strength) and further incorporated into the hydrogel bases to possess a dual rationale of protection against burst release and enhanced solubility of the drug. The optimized hydrogel formulation (NV-TPGS-3-GG-4) showed ideal rheological behavior and in situ characteristics at 37±0.5°C with sustained release of more than 144 h. The optimized formulation had instant in vitro gelation (2.8±0.3 min) with good injectability in comparison to the conventional commercial DTX injectable formulation having instant release (<2 h). Additionally, developed formulation exhibited an improved biodisponibility (25.1±0.2 h) in comparison to the commercially available formulation (1.7±0.1 h). The Solid Tumor Carcinoma model in Swiss albino mice revealed that the optimized formulation (based on gellan gum) showed better tumor reduction (85.7±1.2%) and lower toxicity as compared to the commercial formulation (77.3±1.3%). Pharmacokinetic and biodistribution studies demonstrated 3 to 4 times higher localization of drug in tumors. Our findings suggested that injectable gellan gum-based in situ hydrogel formulation can be an effective delivery system for DTX with enhanced solubility, reduced toxicity, and better targeting to the tumors for improved therapeutics.Graphical abstract.


Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanocápsulas/administração & dosagem , Polissacarídeos Bacterianos/administração & dosagem , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Docetaxel/química , Docetaxel/metabolismo , Feminino , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/metabolismo , Camundongos , Nanocápsulas/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
17.
Nat Commun ; 12(1): 2875, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001908

RESUMO

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.


Assuntos
Corticosteroides/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Dexametasona/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Corticosteroides/química , Corticosteroides/farmacocinética , Animais , Células Cultivadas , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Dexametasona/química , Dexametasona/farmacocinética , Dimerização , Modelos Animais de Doenças , Implantes de Medicamento , Liberação Controlada de Fármacos , Polímeros/química , Coelhos , Ratos , Uveíte/metabolismo , Uveíte/prevenção & controle
18.
Carbohydr Polym ; 262: 117933, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838810

RESUMO

Carboxymethyl chitosan (CMCS) has emerged as a promising biopolymer carrier for controlled release formulations of pesticide. In this study, manganese-based carboxymethyl chitosan hydrogel was facilely prepared to encapsulate and release fungicide prothioconazole in a controllable manner. The loading content (LC) and encapsulation efficiency (EE) of prothioconazole were optimized by orthogonal test. When scaled up under the optimal condition, the corresponding LC and EE were 22.17 % and 68.38 %, respectively. The result showed that the pH-triggered release behavior of prothioconazole for the hydrogels was consistent with swelling behavior. The pesticide rapidly released in neutral and slightly alkaline solutions than in acidic conditions. Moreover, the prepared hydrogel showed enhanced fungicidal ability against wheat take-all pathogen (Gaeumannomyces graminis var. tritic) compared to that of prothioconazole technical material. This research seeks to provide a promising approach to develop metal and polysaccharide-based hydrogels to control the pesticide release and reduce pesticide use in sustainable agriculture application.


Assuntos
Quitosana/análogos & derivados , Fungicidas Industriais/farmacologia , Hidrogéis/química , Manganês/química , Triazóis/farmacologia , Ascomicetos/efeitos dos fármacos , Quitosana/química , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fungicidas Industriais/química , Concentração de Íons de Hidrogênio , Praguicidas/química , Praguicidas/farmacologia , Triazóis/química , Triticum/microbiologia
19.
Carbohydr Polym ; 262: 117952, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838828

RESUMO

Nowadays, drug encapsulation and drug release from cellulose nanofibrils systems are intense research topics, and commercial grades of cellulose nanomaterials are currently available. In this work we present an ester-containing prodrug of metronidazole that is covalently bound to cellulose nanofibrils in aqueous suspension through a two-step immobilization procedure involving green chemistry principles. The presence of the drug is confirmed by several characterization tools and methods such as Raman spectroscopy, elemental analysis, Dynamic Nuclear Polarization enhanced NMR. This technique allows enhancing the sensitivity of NMR by several orders of magnitude. It has been used to study cellulose nanofibrils substrates and it appears as the ultimate tool to confirm the covalent nature of the binding through thiol-yne click chemistry. Moreover, the ester function of the immobilized prodrug can be cleaved by specific enzyme activity thus allowing controlled drug release.


Assuntos
Celulose/química , Química Click/métodos , Metronidazol/química , Nanofibras/química , Pró-Fármacos/química , Antibacterianos/química , Óxidos N-Cíclicos/química , Preparações de Ação Retardada/química , Humanos , Espectroscopia de Ressonância Magnética/métodos , Oxirredução , Análise Espectral Raman/métodos , Compostos de Sulfidrila/química , Água/química
20.
Int J Biol Macromol ; 182: 333-342, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798589

RESUMO

Drug delivery devices are attractive alternatives to drugs usually orally administrated. Therefore, this work aimed to produce PLA/PBAT-based nanofibers for the controlled release of cilostazol, evaluating the effect of different drug concentrations (20 and 30%) over the properties of the fibers. The fibers were characterized by scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), x-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric (TG/DTG), and mechanical analysis. SEM results indicated a high concentration of drug crystals on the surface of the fibers that contained 20% of cilostazol. These fibers were also thinner, more crystalline, less thermally stable, and less fragile in comparison to the fibers containing 30% of cilostazol, according to the XRD, DSC, TG/DTG, and mechanical results. The controlled release assays indicated that the fibers containing 20% of cilostazol would be attractive for short-term releases, reaching the equilibrium after approximately 6 h, while the ones containing 30% would ensure a slower release (~ 12 h). Despite the differences, both fibers would improve and enhance the efficiency of the treatment, and they would also prevent possible side effects caused by the drug to the gastric system.


Assuntos
Cilostazol/administração & dosagem , Preparações de Ação Retardada/química , Nanofibras/química , Poliésteres/química , Varredura Diferencial de Calorimetria , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
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