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1.
Chem Pharm Bull (Tokyo) ; 67(9): 921-928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474730

RESUMO

We studied the possibility of using ursodeoxycholic acid (UDCA) as an excipient to create an amorphous composite that can be administered to animals in preclinical studies of experimental drugs. Three UDCA-based amorphous samples composed of nifedipine (NIF), indomethacin (IND), and naproxen (NAP) were found by screening. The UDCA-based formulations were adjudged amorphous by solid-state analysis using X-ray powder diffraction and differential scanning calorimetry. In addition, amorphous samples of NIF-UDCA, IND-UDCA, and NAP-UDCA did not crystallize while in 1% methyl cellulose (MC) solution for 120 min, although an amorphous solid dispersion of NIF-poly(vinylpyrrolidone) (PVP) crystallized rapidly. The low hygroscopicity of UDCA helps NIF maintain an amorphous state in 1% MC solution. The UDCA-based amorphous composites can be administered as suspended formulations to animals in preclinical studies.


Assuntos
Composição de Medicamentos , Preparações Farmacêuticas/química , Ácido Ursodesoxicólico/química , Varredura Diferencial de Calorimetria , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Indometacina/química , Naproxeno/química , Nifedipino/química , Solubilidade
2.
Chem Pharm Bull (Tokyo) ; 67(9): 992-999, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474738

RESUMO

A three-dimensional (3D) printer is a powerful tool that can be used to enhance personalized medicine. A fused deposition modeling (FDM) 3D printer can fabricate 3D objects with different internal structures that provides the opportunity to introduce one or more specific functionalities. In this study, zero-order sustained-release floating tablet was fabricated using FDM 3D printer. Filaments comprising poorly water-soluble weak base drug, itraconazole (ITZ) and polymers (hydroxypropyl cellulose and polyvinylpyrrolidone) were prepared, and tablets with a hollow structure and different outside shell thicknesses were fabricated. In the 3D printed tablets, ITZ existed as an amorphous state and its solubility improved markedly. As the outside shell thickness of the tablet increased, drug release was delayed and floating time was prolonged. In the tablets with 0.5 mm of the upper and bottom layer thickness and 1.5 mm of the side layer thickness, holes were not formed in the tablets during the dissolution test, and the tablets floated for a long period (540 min) and showed nearly zero-order drug release for 720 min. These findings may be useful for improving the bioavailability of several drugs by effective absorption from the upper small intestine, with floating gastric retention system.


Assuntos
Itraconazol/química , Impressão Tridimensional , Comprimidos/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Liberação Controlada de Fármacos , Cinética , Polímeros/química , Solubilidade , Difração de Raios X
3.
AAPS PharmSciTech ; 20(7): 274, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385095

RESUMO

With the increase concern of solubilization for insoluble drug, ternary solid dispersion (SD) formulations developed more rapidly than binary systems. However, rational formulation design of ternary systems and their dissolution molecular mechanism were still under development. Current research aimed to develop the effective ternary formulations and investigate their molecular mechanism by integrated experimental and modeling techniques. Glipizide (GLI) was selected as the model drug and PEG was used as the solubilizing polymer, while surfactants (e.g., SDS or Tween80) were the third components. SD samples were prepared at different weight ratio by melting method. In the dissolution tests, the solubilization effect of ternary system with very small amount of surfactant (drug/PEG/surfactant 1/1/0.02) was similar with that of binary systems with high polymer ratios (drug/PEG 1/3 and 1/9). The molecular structure of ternary systems was characterized by differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscope (SEM). Moreover, molecular dynamic (MD) simulations mimicked the preparation process of SDs, and molecular motion in solvent revealed the dissolution mechanism of SD. As the Gordon-Taylor equation described, the experimental and calculated values of Tg were compared for ternary and binary systems, which confirmed good miscibility of GLI with other components. In summary, ternary SD systems could significantly decrease the usage of polymers than binary system. Molecular mechanism of dissolution for both binary and ternary solid dispersions was revealed by combined experiments and molecular modeling techniques. Our research provides a novel pathway for the further research of ternary solid dispersion formulations.


Assuntos
Glipizida/química , Modelos Moleculares , Polietilenoglicóis/química , Polissorbatos/química , Varredura Diferencial de Calorimetria/métodos , Glipizida/análise , Hipoglicemiantes/análise , Hipoglicemiantes/química , Polietilenoglicóis/análise , Polímeros/análise , Polímeros/química , Polissorbatos/análise , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tensoativos/análise , Tensoativos/química , Difração de Raios X/métodos
4.
Int J Nanomedicine ; 14: 5381-5396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409994

RESUMO

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.


Assuntos
Derme/metabolismo , Lipídeos/química , Nanopartículas/química , Tacrolimo/farmacologia , Temperatura Ambiente , Administração Cutânea , Animais , Varredura Diferencial de Calorimetria , Derme/efeitos dos fármacos , Liberação Controlada de Fármacos , Irritantes/toxicidade , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Ratos Sprague-Dawley , Absorção Cutânea/efeitos dos fármacos , Testes Cutâneos , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Difração de Raios X
5.
Int J Nanomedicine ; 14: 5435-5448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409997

RESUMO

Background: Ramipril (RMP) suffers from poor aqueous solubility along with sensitivity to mechanical stress, heat, and moisture. The aim of the current study is to improve RMP solubility and stability by designing solid self-nanoemulsifying drug delivery system (S-SNEDDS) as tablet. Methods: The drug was initially incorporated in different liquid formulations (L-SNEDDS) which were evaluated by equilibrium solubility, droplet size, and zeta potential studies. The optimized formulation was solidified into S-SNEDDS powder by the adsorbent Syloid® and compressed into a self-nanoemulsifying tablet (T-SNEDDS). The optimized tablet was evaluated by drug content uniformity, hardness, friability, disintegration, and dissolution tests. Furthermore, pure RMP, optimized L-SNEDDS, and T-SNEDDS were enrolled in accelerated and long-term stability studies. Results: Among various liquid formulations, F5 L-SNEDDS [capmul MCM/transcutol/HCO-30 (25/25/50%w/w)] showed relatively high drug solubility, nano-scaled droplet size, and high negative zeta potential value. The optimized SNEDDS solidification with Syloid® at ratio (1:1) resulted in a compressible powder with an excellent flowability. The optimized tablet (T-SNEDDS) showed accepted content uniformity, hardness, friability, and disintegration time (<15 minutes). The optimized L-SNEDDS, S-SNEDDS, and T-SNEDDS showed superior enhancement of RMP dissolution compared to the pure drug. Most importantly, T-SNEDDS showed significant (P<0.05) improvement of RMP stability compared to the pure drug and L-SNEDDS in both accelerated and long-term stability studies. Conclusion: RMP-loaded T-SNEDDS offers a potential oral dosage form that provides combined improvement of RMP dissolution and chemical stability.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanopartículas/química , Ramipril/farmacologia , Administração Oral , Adsorção , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Dureza , Nanopartículas/ultraestrutura , Tamanho da Partícula , Controle de Qualidade , Solubilidade , Eletricidade Estática , Comprimidos/química , Fatores de Tempo , Difração de Raios X
6.
Int J Nanomedicine ; 14: 5397-5413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409995

RESUMO

Background: Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage.  It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. Purpose: The objective of this study was to prepare and optimize nontoxic, biocompatible ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. Methods: ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using  ß-CD  as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Results: Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R2 and "n" value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. Conclusion: A novel pH responsive crosslinked network containing ß-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.


Assuntos
Bentonita/química , Hidrogéis/química , Lovastatina/administração & dosagem , Metacrilatos/química , Nanocompostos/química , beta-Ciclodextrinas/química , Acrilamidas/química , Administração Oral , Animais , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Lipídeos/sangue , Nanocompostos/ultraestrutura , Especificidade de Órgãos , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Resistência à Tração , Termogravimetria , Testes de Toxicidade Aguda , Difração de Raios X
7.
Int J Nanomedicine ; 14: 5503-5526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410001

RESUMO

Background and purpose: Glioma is one of the most aggressive primary brain tumors and is incurable. Surgical resection, radiation, and chemotherapies have been the standard treatments for brain tumors, however, they damage healthy tissue. Therefore, there is a need for safe anticancer drug delivery systems. This is particularly true for natural prodrugs such as thymoquinone (TQ), which has a high therapeutic potential for cancers but has poor water solubility and insufficient targeting capacity. We have tailored novel core-shell nanoformulations for TQ delivery against glioma cells using mesoporous silica nanoparticles (MSNs) as a carrier. Methods: The core-shell nanoformulations were prepared with a core of MSNs loaded with TQ (MSNTQ), and the shell consisted of whey protein and gum Arabic (MSNTQ-WA), or chitosan and stearic acid (MSNTQ-CS). Nanoformulations were characterized, studied for release kinetics and evaluated for anticancer activity on brain cancer cells (SW1088 and A172) and cortical neuronal cells-2 (HCN2) as normal cells. Furthermore, they were evaluated for caspase-3, cytochrome c, cell cycle arrest, and apoptosis to understand the possible anticancer mechanism. Results: TQ release was pH-dependent and different for core and core-shell nanoformulations. A high TQ release from MSNTQ was detected at neutral pH 7.4, while a high TQ release from MSNTQ-WA and MSNTQ-CS was obtained at acidic pH 5.5 and 6.8, respectively; thus, TQ release in acidic tumor environment was enhanced. The release kinetics fitted with the Korsmeyer-Peppas kinetic model corresponding to diffusion-controlled release. Comparative in vitro tests with cancer and normal cells indicated a high anticancer efficiency for MSNTQ-WA compared to free TQ, and low cytotoxicity in the case of normal cells. The core-shell nanoformulations significantly improved caspase-3 activation, cytochrome c triggers, cell cycle arrest at G2/M, and apoptosis induction compared to TQ. Conclusion: Use of MSNs loaded with TQ permit improved cancer targeting and opens the door to translating TQ into clinical application. Particularly good results were obtained for MSNTQ-WA.


Assuntos
Antineoplásicos/uso terapêutico , Benzoquinonas/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Glioma/tratamento farmacológico , Nanopartículas/química , Dióxido de Silício/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Materiais Biocompatíveis/química , Encéfalo/patologia , Varredura Diferencial de Calorimetria , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quitosana/química , Citocromos c/metabolismo , Difusão , Ativação Enzimática/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Cinética , Nanopartículas/ultraestrutura , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
8.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
9.
Phys Chem Chem Phys ; 21(35): 19686-19694, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31469369

RESUMO

In this study the glass transition temperatures (Tgα and Tgß) in mesoporous silica-based amorphous drugs were characterized. For this purpose, mesoporous silica Parteck SLC (MPS) was loaded with the drugs ibuprofen and carvedilol, either below, at, or above the monomolecular drug loading capacities, i.e. the concentration at which the entire MPS surface is covered with a monolayer of drug molecules. The resulting amorphous forms were analysed using X-ray powder diffraction and the thermal behaviour was characterised with differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The drug monolayer did not contribute to the thermal signal in DSC. Using DMA however, it could be shown that the monolayer indeed exhibited a very weak Tgα, and that the temperature range of this transition did not differ from that of the quench cooled amorphous drugs. Theoretical ab initio molecular dynamics simulations revealed that the nature of hydrogen bonding geometry of the functional groups interacting with the MPS surface were similar to that of the respective crystalline drugs, which results in restricted molecular motions for those functional groups. On the other hand, the non-interacting parts of the molecules exhibited molecular motions similar to what is observed in pure amorphous drugs. As a result of the interactions of the monolayer with the MPS surface, the monomolecular drug layer did not reveal a Tgß. However, a Tgß was found at any drug-MPS ratios above the monomolecular drug loading capacity as a result of the excess drug which forms a "true" amorphous phase. Overall, this study demonstrated that drug molecules forming an amorphous monolayer on the surfaces of a mesoporous silica particle, even though they are restricted in their mobility, exhibit a Tgα, but lack a Tgß, whereas any excess drug confined in the MPS pores showed similar properties as the pure amorphous drug. These findings will help to increase the overall understanding of drug loaded MS systems, including their physical stability as well as release properties.


Assuntos
Vidro/química , Dióxido de Silício/química , Temperatura de Transição , Varredura Diferencial de Calorimetria , Carvedilol/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Ibuprofeno/química , Simulação de Dinâmica Molecular
10.
Chem Pharm Bull (Tokyo) ; 67(8): 816-823, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366831

RESUMO

In this present study a new co-crystals of zoledronic acid with DL-tartaric acid and nicotinamide has been developed with improved solubility. Zoledronic acid is a class III drug with poor oral bioavailability due to its poor permeability and low aqueous solubility; hence an attempt has been made to improve its solubility by co-crystallization technology. Pharmaceutical cocrystals are multi-component crystals with a stoichiometric ratio of active pharmaceutical ingredients (APIs) and cocrystal coformers (CCFs) that are assembled by noncovalent interactions such as hydrogen bonds, π-π packing, and Vander Waals forces. In this study the coformers selected were DL-tartaric acid and nicotinamide based on ease of hydrogen bond formation. The co-crystal of zoledronic acid with DL-tartaric acid were prepared in three ratios (1 : 1, 1 : 2 and 2 : 1) by slow solvent evaporation method and with nicotinamide in 1 : 1 ratio by dry grinding method. The formation of co-crystal was confirmed by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT)IR. The dynamic solubility of co-crystals with DL-tartaric acid in the ratios 1 : 1, 1 : 2 and 2 : 1 increased by fold as compared to pure drug.


Assuntos
Desenho de Drogas , Niacinamida/química , Tartaratos/química , Ácido Zoledrônico/química , Varredura Diferencial de Calorimetria , Cristalização , Estrutura Molecular , Difração de Pó , Solubilidade , Ácido Zoledrônico/síntese química
11.
Food Chem ; 299: 125133, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31323441

RESUMO

The aim of this study was to investigate the effect of NaCl on the formation, structure and property of samples formed from wheat starch (WS) and the fatty acids (lauric acid (LA), myristic acid (MA), palmitic acid (PA) and stearic acid (SA)). Results from RVA, DSC, XRD and Raman analyses showed that LA, and to a lesser extent MA, formed complexes with WS. Under the experimental conditions used, only minor amounts of WS-PA and WS-SA complexes formed. The low solubility of PA and SA, and to some extent MA, in water caused these fatty acids to mostly self-aggregate. The presence of NaCl promoted the formation of WS-LA complexes and, to a lesser extent complexes with MA, but had little effect on the formation of WS-PA and WS-SA complexes. Solubility of fatty acids in aqueous medium was proposed to be a major factor for the formation of starch-fatty acid complexes.


Assuntos
Ácidos Graxos/química , Lipídeos/química , Cloreto de Sódio/química , Amido/química , Triticum/química , Varredura Diferencial de Calorimetria , Solubilidade , Análise Espectral Raman , Viscosidade , Difração de Raios X
12.
Int J Nanomedicine ; 14: 4383-4395, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354267

RESUMO

Background: The bioactive compounds glycyrrhizin (GL) and thymoquinone (TQ) have been reported for antidiabetic activity in pure and nanoformulation (NF) form. However, the antidiabetic effect of a combined nanoformulation of these two has not been reported in the literature. Here, a combinational nanomedicine approach was investigated to enhance the antidiabetic effects of the two bioactive compounds of GL and TQ (GT), in type 2 diabetic rats in reference to metformin. Methods: Two separately prepared NFs of GL (using polymeric nanoparticles) and TQ (using polymeric nanocapsules) were mixed to obtain a therapeutic cargo of nanomedicine and then characterized with respect to particle size, stability, morphology, chemical interaction, and in vivo behavior. Additionally, NFs were evaluated for their cytotoxic effect on Vero cell lines compared to the pure form. This nanomedicine was administered orally, both independently and in combination (pure form or NF) for 21 successive days to type 2 diabetic rats and the effect assessed in term of body weight, fasting blood-glucose level, and various biochemical parameters (such as lipid-profile parameters and HbA1c). Results: When these nanomedicines were applied in combined rather than individual forms, significant decreases in blood glucose and HbA1c and significant improvements in body weight and lipid profile were observed, despite them containing lower amounts than the pure forms. The treatment of diabetic rats with GL and TQ, when administered independently in either pure or NF forms, did not lead to favorable trends in any studied parameters. Conclusion: The administration of combined GT NFs exhibited significant improvement in studied parameters. Improvements in antidiabetic activity could have been due to a synergistic effect of combined NFs, leading to enhanced absorption of NFs and lesser cytotoxic effects compared to pure bioactive compounds. Therefore, GT NFs demonstrated potential as a new medicinal agent for the management of diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Composição de Medicamentos , Hipoglicemiantes/uso terapêutico , Nanopartículas/química , Polímeros/química , Animais , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Feminino , Hemoglobina A Glicada/metabolismo , Ácido Glicirrízico/uso terapêutico , Hipoglicemiantes/administração & dosagem , Lipídeos/química , Nanopartículas/ultraestrutura , Niacinamida , Polímeros/efeitos adversos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Estreptozocina
13.
Food Chem ; 298: 125045, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31261002

RESUMO

In this study, sacha inchi oil (SIO) (Plukenetia volubilis L.) was microencapsulated via complex coacervation of ovalbumin (OVA) and sodium alginate (AL), and the microcapsule properties were characterized. The omega-3 content in the SIO was evaluated after in vitro gastric simulation and microencapsulation. The coacervate complex between OVA and AL was evaluated based on electrostatic interactions and developed for use as a wall material via the SIO microencapsulation process. The best mass ratio for the biopolymers (OVA:AL) was 4:1 at pH 3.8, and the complex exhibited a thermal resistance at 189.86 °C. The SIO microcapsules showed a high encapsulation efficiency of approximately 94.12% in the ratio (OVA:AL) of 1:1. Furthermore, microencapsulated SIO presented resistance under gastric conditions with a low release of acyl (ω-3) units. These results demonstrate that it is possible to use OVA:AL as encapsulating agents to protect bioactive compounds and to improve the thermal behavior of microcapsules.


Assuntos
Composição de Medicamentos/métodos , Euphorbiaceae/metabolismo , Óleos Vegetais/química , Alginatos/química , Varredura Diferencial de Calorimetria , Cápsulas/química , Euphorbiaceae/química , Ácidos Graxos Ômega-3/química , Concentração de Íons de Hidrogênio , Ovalbumina/química , Eletricidade Estática
14.
Int J Nanomedicine ; 14: 4589-4599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296988

RESUMO

Purpose: Ferulic acid (FA) is a poorly water-soluble natural antioxidant with anticancer activity. This poor solubility limits the application of FA in the food and pharmaceutical industry. Cyclodextrin nanosponges (CD-NSs) are a novel group of cross-linked CD derivatives which can be used to enhance the solubility of low-soluble bioactive compounds. Methods: In this study, FA was encapsulated into the NSs in the proportion of 1:4 (FA:NS). Diphenyl carbonate was used as a cross-linker in different proportions with ß-CD. Characterization of obtained NSs was performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis. Results: Our results revealed that the solubility of encapsulated FA was increased up to fifteenfold compared with pure FA in the proportion of 1:4 (CD:cross-linker). The results of FTIR, XRD, and DSC confirmed the interaction of FA with NSs. The cytotoxicity of encapsulated FA against MCF7 and 4T1 breast cancer cell lines was investigated using different concentrations of FA in 24, 48, and 72 hrs. The cytotoxicity assay indicated that FA treatment reduced viability and enhanced apoptosis of cancer cells. IC50 value of encapsulated FA (250 ppm) was decreased by threefold when compared with pure FA (750 ppm). Conclusion: In general, CD-NS was found to be a suitable delivery system for poorly soluble bioactives such as FA.


Assuntos
Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Ciclodextrinas/química , Nanoestruturas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Varredura Diferencial de Calorimetria , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Microscopia Eletrônica de Varredura , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X
15.
Food Chem ; 298: 125064, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260954

RESUMO

Edible films based on gelatin and chitosan have high gas and aroma barrier properties. This study focused on their capability to sorbed/retain aroma compounds (1-hexanal, 2-hexen-1-ol, 1-hexanol, 3-hexanone and phenol) at three relative humidity level (≤2%, 53% or 84% RH). Whatever the relative humidity condition, the order of sorption is keton (3-hexanone) < aldehyde (1-hexanal) < aliphatic alcohols (2-hexen-1-ol and 1-hexanol) < phenol. This order could be related to the intrinsic chemical properties of aroma compounds. The increase in moisture enhanced the sorption at the highest RH for all the aroma compounds. However, a competition between water and aliphatic alcohols is observed at 53%RH. All compounds have an ideal sorption behaviour (logarithmic increase) except 1-hexanal. The sorption of 1-hexanal, 1-hexanol, 2-hexen-1-ol and 3-hexanone induced an antiplasticization of the network by increasing the film Tg by more than 5 °C. On the contrary, phenol was an efficient plasticizer at least as high as moisture.


Assuntos
Quitosana/química , Gelatina/química , Compostos Orgânicos Voláteis/química , Adsorção , Álcoois/química , Varredura Diferencial de Calorimetria , Cromatografia Gasosa , Umidade , Cetonas/química , Cinética , Fenol/química , Temperatura Ambiente
16.
Food Chem ; 299: 125122, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31288165

RESUMO

To ease the mass exchange in fruit tissues, cutting and blanching are traditionally performed. However, recently, unconventional methods such as sonication are becoming more popular, which cause several alterations of physical and chemical properties as well as microstructure changes. The aim of this work was to evaluate the distribution of water inside the cranberry fruits, microstructural changes and sugars content, following traditional and sonication pre-treatments in osmotic solutions. TD-NMR spectroscopy was used to measure the transverse relaxation time (T2) and intensity of proton pools in different cellular compartments. The microstructure of the samples was evaluated by SEM microscopy, sugars content by HPLC and sucrose melting temperature and enthalpy by DSC. Different pre-treatments appeared to promote microstructure alterations and loss of water from vacuole and cytoplasm/extracellular space, more pronounced in cut and blanched samples. Cutting and blanching followed by osmotic dehydration with assisted sonication eased sucrose penetration into the tissue.


Assuntos
Conservação de Alimentos/métodos , Frutas/química , Açúcares/análise , Vaccinium macrocarpon/química , Água/metabolismo , Varredura Diferencial de Calorimetria , Dessecação , Frutas/ultraestrutura , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Osmose , Sonicação , Sacarose/análise , Temperatura Ambiente , Vaccinium macrocarpon/ultraestrutura
17.
Int J Nanomedicine ; 14: 4649-4666, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303753

RESUMO

Introduction: Herein, a hyaluronic acid (HA)-coated redox-sensitive chitosan-based nanoparticle, HA(HECS-ss-OA)/GA, was successfully developed for tumor-specific intracellular rapid delivery of gambogic acid (GA). Materials and methods: The redox-sensitive polymer, HECS-ss-OA, was prepared through a well-controlled synthesis procedure with a satisfactory reproducibility and stable resulted surface properties of the assembled cationic micelles. GA was solubilized into the inner core of HECS-ss-OA micelles, while HA was employed to coat outside HECS-ss-OA/GA for CD44-mediated active targeting along with protection from cation-associated in vivo defects. The desirable redox-sensitivity of HA(HECS-ss-OA)/GA was demonstrated by morphology and particle size changes alongside in vitro drug release of nanoparticles in different simulated reducing environments. Results: The results of flow cytometry and confocal microscopy confirmed the HA-receptor mediated cellular uptake and burst drug release in highly reducing cytosol of HA(HECS-ss-OA)/GA. Consequently, HA(HECS-ss-OA)/GA showed the highest apoptosis induction and cytotoxicity over the non-sensitive (HA(HECS-cc-OA)/GA) and HA un-coated (HECS-ss-OA/GA) controls against A549 NSCLC model both in vitro and in vivo. Furthermore, a diminished systemic cytotoxicity was observed in HA(HECS-ss-OA)/GA treated mice compared with those treated by HA un-coated cationic ones and GA solution.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Hialurônico/química , Micelas , Neoplasias/tratamento farmacológico , Xantonas/administração & dosagem , Xantonas/uso terapêutico , Células A549 , Animais , Antineoplásicos/farmacologia , Apoptose , Varredura Diferencial de Calorimetria , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/síntese química , Humanos , Ácido Hialurônico/síntese química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias/patologia , Oxirredução , Propionatos/síntese química , Propionatos/química , Espectroscopia de Prótons por Ressonância Magnética , Reprodutibilidade dos Testes , Distribuição Tecidual/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Xantonas/farmacologia
18.
Int J Nanomedicine ; 14: 4949-4960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308665

RESUMO

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Luz , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Metotrexato/sangue , Metotrexato/farmacocinética , Petróleo , Transição de Fase , Ratos Sprague-Dawley , Solubilidade , Difração de Raios X
19.
Int J Nanomedicine ; 14: 4961-4974, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308666

RESUMO

Background: Lipid polymer hybrid nanoparticles (LPHNPs) for the controlled delivery of hydrophilic doxorubicin hydrochloride (DOX.HCl) and lipophilic DOX base have been fabricated by the single step modified nanoprecipitation method. Materials and methods: Poly (D, L-lactide-co-glicolide) (PLGA), lecithin, and 1,2-distearoyl-Sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000 (DSPE-PEG 2000) were selected as structural components. Results: The mean particle size was 173-208 nm, with an encapsulation efficiency of 17.8±1.9 to 43.8±4.4% and 40.3±0.6 to 59. 8±1.4% for DOX.HCl and DOX base, respectively. The drug release profile was in the range 33-57% in 24 hours and followed the Higuchi model (R2=0.9867-0.9450) and Fickian diffusion (n<0.5). However, the release of DOX base was slower than DOX.HCl. The in vitro cytotoxicity studies and confocal imaging showed safety, good biocompatibility, and a higher degree of particle internalization. The higher internalization of DOX base was attributed to higher permeability of lipophilic component and better hydrophobic interaction of particles with cell membranes. Compared to the free DOX, the DOX.HCl and DOX base loaded LPHNPs showed higher antiproliferation effects in MDA-MB231 and PC3 cells. Conclusion: Therefore, LPHNPs have provided a potential drug delivery strategy for safe, controlled delivery of both hydrophilic and lipophilic form of DOX in cancer cells.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Nanopartículas/química , Polímeros/química , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Coloides/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Cinética , Nanopartículas/ultraestrutura , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
20.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2236-2243, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359648

RESUMO

The single-factor test was used to optimize the high-pressure homogenization method to prepare the phenolic extract nanosuspensions(DBNs). The physicochemical properties of the obtained nanosuspensions were characterized and the cumulative release in vitro was evaluated. The results showed that the drug concentration was 0.5 g·L~(-1), the mass concentrations of PVPK30 and SDS were 0.5 and 0.25 g·L~(-1), respectively, the probe ultrasonic time was 5 min, the homogenization pressure was 900 bar, and the number of homogenization was 2 times. The prepared DBNs had an average particle size of(168.80±0.36) nm, polydispersity index(PDI) of 0.09±0.04, stability index(SI) of 0.85, and DBNs were stable for storage within 30 days. Scanning electron microscopy showed that the particle size of the dragon's blood extract was reduced and the uniformity was improved in the obtained nanosuspensions. X-ray diffraction pattern and differential scanning calorimetry showed that the phenolic extract of dragon's blood was still in an amorphous state after being prepared into nanosuspensions. The results of saturated solubility measurement showed that the solubility of DBNs lyophilized powder reached 6.25 g·L~(-1), while the solubility of DB raw powder was only 28.67 mg·L~(-1). The in vitro dissolution experiments showed that DBNs lyophilized powder accumulated in gastrointestinal fluid for 8 h. The release amount was 90%,the cumulative release of the raw powder in the gastrointestinal fluid for 24 h was less than 1%, and the solubility and dissolution rate of the DBNs lyophilized powder were significantly higher than the DB raw powder. The method is simple in process and convenient in operation, and can successfully prepare uniform and stable nanosuspensions to improve its solubility, and provides a research basis for solving the application limitation of dragon's blood extract.


Assuntos
Nanopartículas , Extratos Vegetais/química , Varredura Diferencial de Calorimetria , Tamanho da Partícula , Solubilidade , Suspensões , Difração de Raios X
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