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1.
Biosensors (Basel) ; 12(9)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36140080

RESUMO

In the present work, we described the preparation and characterization of the micelles based on amphiphilic poly(ε-caprolactone-block-ethylene glycol) block copolymer (PCL-b-PEG) loaded with non-symmetric [Pt(C^N*N'^C')] complex (Pt1) (where C^N*N'^C': 6-(phenyl(6-(thiophene-2-yl)pyridin-2-yl)amino)-2-(tyophene-2-yl)nicotinate). The obtained nanospecies displayed the ignition of near-infrared (NIR) phosphorescence upon an increase in the content of the platinum complexes in the micelles, which acted as the major emission component at 12 wt.% of Pt1. Emergence of the NIR band at 780 nm was also accompanied by a 3-fold growth of the quantum yield and an increase in the two-photon absorption cross-section that reached the value of 450 GM. Both effects are believed to be the result of progressive platinum complex aggregation inside hydrophobic poly(caprolactone) cores of block copolymer micelles, which has been ascribed to aggregation induced emission (AIE). The resulting phosphorescent (Pt1@PCL-b-PEG) micelles demonstrated pronounced sensitivity towards molecular oxygen, the key intracellular bioanalyte. The detailed photophysical analysis of the AIE phenomena revealed that the NIR emission most probably occurred due to the excimeric excited state of the 3MMLCT character. Evaluation of the Pt1@PCL-b-PEG efficacy as a lifetime intracellular oxygen biosensor carried out in CHO-K1 live cells demonstrated the linear response of the probe emission lifetime towards this analyte accompanied by a pronounced influence of serum albumin on the lifetime response. Nevertheless, Pt1@PCL-b-PEG can serve as a semi-quantitative lifetime oxygen nanosensor. The key result of this study consists of the demonstration of an alternative approach for the preparation of NIR biosensors by taking advantage of in situ generation of NIR emission due to the nanoconfined aggregation of Pt (II) complexes inside the micellar nanocarriers.


Assuntos
Técnicas Biossensoriais , Niacina , Caproatos , Etilenoglicóis/química , Lactonas , Micelas , Oxigênio , Platina , Poliésteres , Polietilenoglicóis/química , Polímeros/química , Albumina Sérica , Tiofenos
2.
Molecules ; 27(3)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35164335

RESUMO

Recent studies have highlighted the benefit of repurposing oral erlotinib (ERL) treatment in some rare skin diseases such as Olmsted syndrome. The use of a topical ERL skin treatment instead of the currently available ERL tablets may be appealing to treat skin disorders while reducing adverse systemic effects and exposure. A method to prepare 0.2% ERL cream, without resorting to a pure active pharmaceutical ingredient, was developed and the formulation was optimized to improve ERL stability over time. Erlotinib extraction from tablets was incomplete with Transcutol, whereas dimethyl sulfoxide (DMSO) allowed 100% erlotinib recovery. During preliminary studies, ERL was shown to be sensitive to oxidation and acidic pH in solution and when added to selected creams (i.e., Excipial, Nourivan Antiox, Pentravan, and Versatile). The results also showed that use of DMSO (5% v/w), neutral pH, as well as a topical agent containing antioxidant substances (Nourivan Antiox) were key factors to maintain the initial erlotinib concentration. The proposed ERL cream formulation at neutral pH contains a homogeneous amount of ERL and is stable for at least 42 days at room temperature in Nourivan cream with antioxidant properties.


Assuntos
Antioxidantes/química , Cloridrato de Erlotinib/síntese química , Creme para a Pele/síntese química , Cromatografia Líquida de Alta Pressão , Dimetil Sulfóxido/química , Composição de Medicamentos , Estabilidade de Medicamentos , Cloridrato de Erlotinib/química , Etilenoglicóis/química , Concentração de Íons de Hidrogênio , Creme para a Pele/química , Comprimidos
3.
Molecules ; 26(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34834144

RESUMO

Between 293.2 and 313.2 K and at 0.1 MPa, the solubility of the weak base, cinnarizine (CNZ) (3), in various {Transcutol-P (TP) (1) + water (2)} combinations is reported. The Hansen solubility parameters (HSP) of CNZ and various {(TP) (1) + water (2)} mixtures free of CNZ were also predicted using HSPiP software. Five distinct cosolvency-based mathematical models were used to link the experimentally determined solubility data of CNZ. The solubility of CNZ in mole fraction was increased with elevated temperature and TP mass fraction in {(TP) (1) + water (2)} combinations. The maximum solubility of CNZ in mole fraction was achieved in neat TP (5.83 × 10-2 at 313.2 K) followed by the minimum in neat water (3.91 × 10-8 at 293.2 K). The values of mean percent deviation (MPD) were estimated as 2.27%, 5.15%, 27.76%, 1.24% and 1.52% for the "Apelblat, van't Hoff, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models", respectively, indicating good correlations. The HSP value of CNZ was closed with that of neat TP, suggesting the maximum solubilization of CNZ in TP compared with neat water and other aqueous mixtures of TP and water. The outcomes of the apparent thermodynamic analysis revealed that CNZ dissolution was endothermic and entropy-driven in all of the {(TP) (1) + water (2)} systems investigated. For {(TP) (1) + water (2)} mixtures, the enthalpy-driven mechanism was determined to be the driven mechanism for CNZ solvation. TP has great potential for solubilizing the weak base, CNZ, in water, as demonstrated by these results.


Assuntos
Cinarizina/química , Etilenoglicóis/química , Termodinâmica , Água/química , Solubilidade
4.
Pharm Dev Technol ; 26(5): 549-558, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33688786

RESUMO

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0-τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs.


Assuntos
Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Excipientes/química , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica/métodos , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Emulsões , Etilenoglicóis/química , Ácidos Oleicos/química , Polietilenoglicóis/química , Coelhos , Solubilidade , Tecnologia Farmacêutica
5.
Biologicals ; 69: 15-21, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33454194

RESUMO

A new, simple and rapid method for the quantitative determination of the antimicrobial preservative 2-phenoxyethanol, based on reverse phase ultra-high-performance liquid chromatography has been developed. The validation was performed according the ICH Q2 guideline "Validation of Analytical Procedures". The desired chromatographic separation was achieved on a Waters Symmetry C18 (150 × 4.6 mm, 5 µm) column using an isocratic elution, with detection at 270 nm wavelength. The mobile phase consisted of acetonitrile/water (55:45, v/v), pumped at a flow rate of 1 mL/min. The calibration curve and the analytical procedure are linear (r2 = 0.999) from the concentration of 0.07 mg/mL to 1.1 mg/mL. The percent relative standard deviation for intra- and inter-day precision was <1%. The recovery of 2-phenoxyethanol in vaccines ranged between 96.5 and 100.60%. The limits of detection and quantitation were 1.3 × 10-4 and 2.7 × 10-4 mg/mL, respectively. The method was found to be robust by changing the column working temperature, the percentage of acetonitrile of the mobile phase and the flow rate. The validated method can be successfully and reliably used to quantify as well as to exclude presence of 2-phenoxyethanol preservative in marketed vaccines.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Etilenoglicóis , Conservantes Farmacêuticos , Vacinas , Acetonitrilas , Etilenoglicóis/química , Humanos , Conservantes Farmacêuticos/química , Vacinas/química
6.
ACS Appl Mater Interfaces ; 13(2): 3089-3097, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33400490

RESUMO

Numerous efforts to fabricate antimicrobial surfaces by simple yet universal protocols with high efficiency have attracted considerable interest but proved to be particularly challenging. Herein, we designed and fabricated a series of antimicrobial polymeric coatings with different functions from single to multiple mechanisms by selectively utilizing diethylene glycol diglycidyl ether (PEGDGE), polylysine, and poly[glycidylmethacrylate-co-3-(dimethyl(4-vinylbenzyl)ammonium)propyl sulfonate] (poly(GMA-co-DVBAPS)) via straightforward mussel-inspired codeposition techniques. Bactericidal polylysine endowed the modified surfaces with a high ability (∼90%) to kill attached bacteria, while PEGDGE components with unique surface hydration prevented bacterial adhesion, avoiding the initial biofilm formation. Moreover, excellent salt-responsive poly(GMA-co-DVBAPS) enabled reactant polymeric coatings to change chain conformations from shrinkable to stretchable state and subsequently release >90% attached bacteria when treated with NaCl solution, even after repeated cycles. Therefore, the obtained polymeric coatings, polydopamine/poly(GMA-co-DVBAPS) (PDA/PDV), polydopamine/polylysine/poly(GMA-co-DVBAPS) (PDA/l-PDV), and polydopamine/polylysine/poly(GMA-co-DVBAPS)/diethylene glycol diglycidyl ether (PDA/l-PDV-PEGDGE), controllably realized functions from single and dual to multiple antimicrobial mechanisms, as evidenced by long-term antifouling activity to bacteria, high bactericidal efficiency, and salt-responsive bacterial regeneration performance with several bacterial killing-release cycles. This study not only contributes to mussel-inspired chemistry for polymeric coatings with controllable functions but also provides a series of reliable and highly efficient antimicrobial surfaces for potential biomedical applications.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Polímeros/química , Polímeros/farmacologia , Animais , Aderência Bacteriana/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Bivalves/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Etilenoglicóis/química , Etilenoglicóis/farmacologia , Humanos , Indóis/química , Indóis/farmacologia , Polilisina/química , Polilisina/farmacologia , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Propriedades de Superfície
7.
J Cereb Blood Flow Metab ; 41(3): 569-578, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32321347

RESUMO

Accumulation of amyloid beta (Aß) is one of the pathological hallmarks of Alzheimer's disease (AD), which can be visualized using [18F]florbetapir positron emission tomography (PET). The aim of this study was to evaluate various parametric methods and to assess their test-retest (TRT) reliability. Two 90 min dynamic [18F]florbetapir PET scans, including arterial sampling, were acquired (n = 8 AD patient, n = 8 controls). The following parametric methods were used; (reference:cerebellum); Logan and spectral analysis (SA), receptor parametric mapping (RPM), simplified reference tissue model2 (SRTM2), reference Logan (rLogan) and standardized uptake value ratios (SUVr(50-70)). BPND+1, DVR, VT and SUVr were compared with corresponding estimates (VT or DVR) from the plasma input reversible two tissue compartmental (2T4k_VB) model with corresponding TRT values for 90-scan duration. RPM (r2 = 0.92; slope = 0.91), Logan (r2 = 0.95; slope = 0.84) and rLogan (r2 = 0.94; slope = 0.88), and SRTM2 (r2 = 0.91; slope = 0.83), SA (r2 = 0.91; slope = 0.88), SUVr (r2 = 0.84; slope = 1.16) correlated well with their 2T4k_VB counterparts. RPM (controls: 1%, AD: 3%), rLogan (controls: 1%, AD: 3%) and SUVr(50-70) (controls: 3%, AD: 8%) showed an excellent TRT reliability. In conclusion, most parametric methods showed excellent performance for [18F]florbetapir, but RPM and rLogan seem the methods of choice, combining the highest accuracy and best TRT reliability.


Assuntos
Doença de Alzheimer/diagnóstico , Compostos de Anilina/química , Etilenoglicóis/química , Compostos Radiofarmacêuticos/química , Idoso , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Radioisótopos de Flúor/química , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
8.
Int J Biol Macromol ; 167: 1290-1296, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33202278

RESUMO

Poly((R)-3-hydroxybutyrate) (P(3HB)) is a polyester that is synthesized and accumulated in many prokaryotic cells. Recently, a new culture method for the secretion of the intracellularly synthesized (R)-3-hydroxybutyrate oligomer (3HBO) from recombinant Escherichia coli cells was developed. In this study, we attempted to produce microbial 3HBO capped with a diethylene glycol terminal (3HBO-DEG) as a macromonomer for polymeric materials. First, we prepared recombinant E. coli strains harboring genes encoding various polyhydroxyalkanoate (PHA) synthases (PhaC, PhaEC or PhaRC) that can incorporate chain transfer (CT) agents such as DEG into the polymer's terminal and generate CT end-capped oligomers. To this end, each strain was cultivated under DEG supplemental conditions, and the synthesis of 3HBO-DEG was confirmed. As a result, the highest secretory production of 3HBO-DEG was observed for the PHA synthase derived from Bacillus cereus YB-4 (PhaRCYB4). To evaluate the usability of the secreted 3HBO-DEG as a macromonomer, 3HBO-DEG was purified from the culture medium and polymerized with 4,4'-diphenylmethane diisocyanate as a spacer compound. Characterization of the polymeric products revealed that 3HBO-based polyurethane was successfully obtained and was a flexible and transparent noncrystalline polymer, unlike P(3HB). These results suggested that microbial 3HBO-DEG is a promising platform building block for synthesizing polyurethane and various other polymers.


Assuntos
Ácido 3-Hidroxibutírico/biossíntese , Aciltransferases/genética , Bacillus cereus/genética , Escherichia coli/genética , Etilenoglicóis/metabolismo , Poliuretanos/química , Poliuretanos/síntese química , Ácido 3-Hidroxibutírico/análise , Ácido 3-Hidroxibutírico/química , Aciltransferases/metabolismo , Cromatografia em Gel , Meios de Cultura , Escherichia coli/metabolismo , Etilenoglicóis/química , Isocianatos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Microrganismos Geneticamente Modificados , Via Secretória/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Termografia
9.
Int J Nanomedicine ; 15: 10453-10467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380795

RESUMO

PURPOSE: Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson's disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD. METHODS AND RESULTS: Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood-brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP+)-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB. CONCLUSION: In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo.


Assuntos
Ginkgolídeos/administração & dosagem , Ginkgolídeos/farmacologia , Lactonas/administração & dosagem , Lactonas/farmacologia , Nanopartículas/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Administração Oral , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cães , Embrião não Mamífero/efeitos dos fármacos , Etilenoglicóis/química , Feminino , Ginkgolídeos/farmacocinética , Humanos , Lactonas/farmacocinética , Células Madin Darby de Rim Canino , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Fármacos Neuroprotetores/administração & dosagem , Poliésteres/química , Ratos Sprague-Dawley , Peixe-Zebra/embriologia
10.
Chem Commun (Camb) ; 56(95): 14962-14975, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33188672

RESUMO

Peroxidase mimics of nanoscale materials as alternatives to natural peroxidases have found widespread uses in biomedicine. Among various types of peroxidase mimics, platinum-group metal (PGM) nanocrystals have drawn considerable attention in recent years due to their superior properties. Particularly, PGM nanocrystals display high catalytic efficiencies, allow for facile surface modifications, and possess excellent stabilities. This feature article summarizes our recent work on development of PGM nanocrystals as peroxidase mimics and exploration of their applications in in vitro diagnostics. We begin with a brief introduction to controlled synthesis of PGM nanocrystals in solution phase. We then elaborate on a variety of physicochemical parameters that can be carefully tuned to optimize the peroxidase-like properties of PGM nanocrystals. Then, we highlight the applications of PGM nanocrystals in different in vitro diagnostic platforms. We conclude this article with personal perspectives on future research directions in this emerging field, where challenges and opportunities are remarked.


Assuntos
Materiais Biomiméticos/química , Corantes/química , Nanopartículas Metálicas/química , Metais/química , Peroxidases/química , Técnicas Biossensoriais , Catálise , Etilenoglicóis/química , Ouro/química , Humanos , Irídio/química , Oxirredução , Paládio/química , Tamanho da Partícula , Platina/química , Polietilenoglicóis/química , Solventes/química , Propriedades de Superfície
11.
Molecules ; 25(21)2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33105792

RESUMO

With the increasing debate on sustainability, there is a strong market trend to formulate more sustainable products for topical application. Several studies emphasize the potential applications of natural, organic, or green chemistry-derived ingredients, but comparative studies between conventional ingredients and sustainable alternatives are lacking. This type of study is considered an excellent baseline and time-saving strategy for future studies. In addition, one of the main challenges of replacing ingredients by sustainable alternatives in topical vehicles is to maintain high-quality products. Thus, the main goal of this research study was to create a well-defined strategy supported by specific experimental data for the development of sustainable topical vehicles with high-quality standards. The study was designed to evaluate the effects of replacing conventional ingredients (e.g., hydrocarbons, silicones, and preservatives) by sustainable ones on the physical, chemical, and microbiological features of topical emulsions. Additionally, in vivo assessment studies were performed to evaluate the safety, biological efficacy, and sensorial aspects of the developed formulations. The results obtained showed that the replacement of ingredients by sustainable alternatives has an effective impact on the physicochemical and structural properties of the emulsions, mainly on their rheological behavior. However, using appropriate strategies for ingredient selection and rheological adjustment, it is possible to overcome some barriers created by the use of natural raw materials, thus developing appealing and high-quality sustainable topical vehicles.


Assuntos
Portadores de Fármacos/química , Emulsões/química , Excipientes/química , Administração Tópica , Dimetilpolisiloxanos/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/efeitos adversos , Composição de Medicamentos , Emulsões/administração & dosagem , Emulsões/efeitos adversos , Etilenoglicóis/química , Vidro/química , Humanos , Hidrocarbonetos/química , Óleos/química , Vaselina/química , Poliésteres/química , Polietilenotereftalatos/química , Reologia , Silicones/química , Ceras/química
12.
Nanotechnology ; 31(47): 475101, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32886644

RESUMO

Nanotherapeutics in cancer treatment are dominating global science and research, and have been recognized as the pioneering medical care regimen. Raloxifene (RLN) has been used for its anti-proliferative action on mammary tissue, however, it suffers from poor oral bioavailability. This investigation gives an account of the design and development of RLN-loaded nanostructured lipid carriers (RLN-NLCs) using a simple and scalable ultrasonication method for improved oral efficacy and limited offsite toxicity using Compritol® 888 ATO as a solid lipid and Transcutol® HP as a liquid lipid. In addition, the optimized RLN-NLCs were in the nanometric range (121 nm) with high % entrapment efficiency (%EE) (81%) for RLN, and were further freeze-dried in the presence of mannitol to enhance the stability of RLN-NLCs in the dry state for long-term use. Morphological observation under a transmission electron microscope and scanning electron microscope revealed the spherical smooth surface nanometric size of RLN-NLCs. Powder x-ray diffraction confirmed the encapsulation of RLN into the RLN-NLC's matrix with reduced crystallinity of the drug. The in vitro release study showed a burst release for an initial 4 h, and sustained release for up to 24 h. Furthermore, the RLN-NLCs showed higher cytotoxicity towards MCF-7 cells in vitro in comparison to RLN suspension, and an ex vivo intestinal permeation study demonstrated improved intestinal permeability of RLN-NLCs. Moreover, the in vivo pharmacokinetic study in female Wistar rats showed a 4.79-fold increment in oral bioavailability of RLN from RLN-NLCs compared to RLN suspension. Taken together, our results pave the way for a new nanotherapeutic approach towards breast cancer treatment.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Etilenoglicóis/química , Ácidos Graxos/química , Cloridrato de Raloxifeno/administração & dosagem , Administração Oral , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Nanoestruturas/química , Cloridrato de Raloxifeno/farmacocinética , Cloridrato de Raloxifeno/farmacologia , Ratos Wistar , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/farmacocinética , Moduladores Seletivos de Receptor Estrogênico/farmacologia
13.
Pharmazie ; 75(9): 417-423, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32797766

RESUMO

Investigation and identification of potential lipids for the manufacture of efavirenz loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) was undertaken. Polymorphic modification and characteristics of the lipids with the best solubilising potential for efavirenz was explored using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Wide-angle X-ray Scattering (WAXS). Lipid screening revealed that EFV is highly soluble in solid and liquid lipids, with glyceryl monostearate (GM) and Transcutol® HP (THP) exhibiting the best solubilising potential for EFV. GM exists in a stable ß-polymorphic modification prior to exposure to heat, but exists in an α-polymorphic modification following exposure to heat. However, it was established that the addition of THP to GM revealed the co-existence of the α- and ß'-polymorphic modifications of the lipid. EFV (60% w/w) exists in a crystalline state in a 70:30 mixture of GM and THP. Investigation of binary mixtures of EFV/GM and GM/THP, in addition to eutectic mixtures of EFV, GM and THP using FT-IR, DSC and WAXS revealed no potential interactions between EFV and the lipids selected for the production of the nanocarriers.


Assuntos
Alcinos/administração & dosagem , Benzoxazinas/administração & dosagem , Ciclopropanos/administração & dosagem , Excipientes/química , Lipídeos/química , Nanopartículas , Alcinos/química , Benzoxazinas/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cristalização , Ciclopropanos/química , Portadores de Fármacos/química , Etilenoglicóis/química , Glicerídeos/química , Temperatura Alta , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/química , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Drug Dev Ind Pharm ; 46(9): 1468-1476, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32715801

RESUMO

OBJECTIVE: Transcutol® is a perfect solubilizer and an effective permeation enhancer of many active substances commonly used in cosmetics. Microemulsions due to the content of surfactant and co-surfactant could be also considered as chemical permeation enhancers that may support transdermal delivery of poorly water- soluble drugs. The purpose of this study was to investigate the effect of Transcutol® and potential microemulsions on diffusion of poorly soluble indomethacin through an artificial membrane and excised rat skin. METHODS: After drug solubilization in different enhancers, drug was dispersed in sodium alginate or carbopol gel used as dermal basis. For characterization of the microemulsions, the basic physico-chemical properties were determined. In vitro as well as ex vivo drug release was determined by vertical Franz cells. RESULTS: Enhancing effect of the examined microemulsions was observed only in carbopol gel. There was an increase in cumulative drug amount released through synthetic membrane by 37.7-39.8% from the microemulsion formulation and 90.6% from Transcutol® formulation within 6 h compared to the control samples. The differences between the permeation curves with or without the content of the enhancers were statistically significant (p < .05). Pearson correlation coefficients indicate a very high degree of dependence (r > 0.9) between in vitro and ex vivo drug release from all dermal vehicles used. CONCLUSION: It can be stated that Transcutol® is the best solubilizer and also penetration enhancer from the examined, and therefore it seems to be effective excipient/solubilizer in topical IND formulation.


Assuntos
Etilenoglicóis/química , Indometacina , Absorção Cutânea , Administração Cutânea , Animais , Géis/química , Géis/metabolismo , Ratos , Pele/metabolismo
15.
Int J Nanomedicine ; 15: 4591-4606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612358

RESUMO

OBJECTIVE: Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study. MATERIALS AND METHODS: Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology. RESULTS: The zeta potential of the mPEG-PCL-ART-NPs was about -38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM. CONCLUSION: These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.


Assuntos
Artemisininas/administração & dosagem , Artemisininas/farmacologia , Gentamicinas/efeitos adversos , Perda Auditiva/tratamento farmacológico , Hidrogéis/administração & dosagem , Animais , Artemisininas/farmacocinética , Sistemas de Liberação de Medicamentos , Etilenoglicóis/química , Gelatina , Cobaias , Células HeLa , Perda Auditiva/induzido quimicamente , Humanos , Hidrogéis/química , Metacrilatos/química , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química
16.
Molecules ; 25(12)2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32545724

RESUMO

The solubility values and thermodynamic parameters of a natural phytomedicine/nutrient piperine (PPN) in Transcutol-HP (THP) + water combinations were determined. The mole fraction solubilities (xe) of PPN in THP + water combinations were recorded at T = 298.2-318.2 K and p = 0.1 MPa by the shake flask method. Hansen solubility parameters (HSPs) of PPN, pure THP, pure water and THP + water mixtures free of PPN were also computed. The xe values of PPN were correlated well with "Apelblat, Van't Hoff, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-Van't Hoff" models with root mean square deviations of < 2.0%. The maximum and minimum xe value of PPN was found in pure THP (9.10 × 10-2 at T = 318.2 K) and pure water (1.03 × 10-5 at T = 298.2 K), respectively. In addition, HSP of PPN was observed more closed with that of pure THP. The thermodynamic parameters of PPN were obtained using the activity coefficient model. The results showed an endothermic dissolution of PPN at m = 0.6-1.0 in comparison to other THP + water combinations studied. In addition, PPN dissolution was recorded as entropy-driven at m = 0.8-1.0 compared with other THP + water mixtures evaluated.


Assuntos
Alcaloides/química , Benzodioxóis/química , Etilenoglicóis/química , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Água/química , Solubilidade , Termodinâmica
17.
Sensors (Basel) ; 20(12)2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32545867

RESUMO

Polymer microgels that respond in a range of neutral pH can be useful for the development of molecular imaging tools and drug-delivery carriers. Here, we describe a simple approach in developing microgels that undergo volume phase transitions and substantial nuclear magnetic resonance (NMR) relaxometric changes within a narrow pH range of 6.4 to 7.4. The pH-responsive microgels were synthesized using methacrylic acid and a series of ethylene glycol dimethacrylate cross-linkers with repeating units of ethylene glycol that range from one to four. NMR relaxometry demonstrated that the transverse relaxation time (T2) of a suspension containing microgels that were cross-linked with diethylene glycol dimethacrylate sharply decreases at the pH where volume phase transition occurs. The polymer microgels cross-linked with 40 and 45 mol% of diethylene glycol dimethacrylate caused about 50% T2 reduction with decreasing pH from 6.8 to 6.4. These results demonstrated that responses of microgels to a range of neutral pH can be easily tuned by using appropriate cross-linkers with certain cross-linking degree. This approach can be useful in developing highly sensitive molecular sensors for magnetic resonance imaging (MRI) of tissue pH values.


Assuntos
Etilenoglicóis/química , Microgéis/química , Ácidos Polimetacrílicos/química , Concentração de Íons de Hidrogênio
18.
Molecules ; 25(11)2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32481525

RESUMO

Digital inkjet printing has been widely used in textile industry. The quality of dye solutions and ink-jet droplets limits the ink-jet printing performance, which is very important for obtaining high-quality ink-jet printing images on fabrics. In this paper, we introduced diethylene glycol (DEG) into the dye solutions of Reactive Blue 49 and Reactive Orange 13, respectively, and investigated the interaction between dye chromophores and DEG molecules. Results indicated that the dye chromophores were featured in the aggregation. Adding DEG into the dye solution could effectively disaggregate clusters of reactive dyes, and eliminate satellite ink droplets, thus improving the resolution of the ink-jet printing image on fabrics. Under the same DEG concentration, the disaggregation effect was more obvious in Orange 13 than in Reactive Blue 49. Higher DEG concentration was required in Reactive Orange 13 solution for creating complete and stable ink drops. The surface tension and viscosity of the dye solutions were measured, and printing performance on cotton fabrics was evaluated. The interaction mechanism between dye chromophores and DEG molecules was also investigated. Results from this work are useful for high-quality ink-jet printing images on fabrics.


Assuntos
Etilenoglicóis/química , Corantes/química , Tensão Superficial , Viscosidade
19.
J Occup Environ Hyg ; 17(7-8): 334-342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469690

RESUMO

Double gloving of disposable gloves is now commonplace in healthcare settings when extra protection is needed against aqueous solutions and especially for antineoplastic drugs in isotonic aqueous media. In the present study, an ASTM F739 2.54 cm cell with closed-loop water collection without recirculation at 35 °C in a moving tray water bath was used to test the permeation of diethylene glycol mono-n-butyl ether (DGBE) through four types of disposable nitrile gloves that were singly and doubly layered in the permeation cell. Samples were taken over 8 hr for capillary gas chromatograph-mass spectrometer quantitation. The breakthrough time (tn) at a permeation of 250 ng/cm2 increased as thickness increased for single layers, but the steady-state permeation rates Ps in µg/cm2/min did not always decrease with increasing thickness. The double-layer tn, Ps and thickness were also more variable relative to a single layer. The thinnest glove with 80 [Formula: see text]m thickness showed a tn = 0-5 min whereas its double layer was 15-20 min. The thickest glove of 132 µm exhibited a tn = 10-15 min but its double layer was tn = 45-55 min. The adjusted double-layer average tn divided by the adjusted single-layer average tn was 4.0 ± 0.8. The adjusted average single-layer Ps divided by the adjusted average double-layer Ps was 3.5 ± 0.8. Other results showed that the average glove swelling was <10%; microscopic and leak testing indicated no penetration and reflectance infrared analysis also showed no chemical changes on the inside glove surfaces. Thus, the permeations were adjudged to obey Fick's First Law of Diffusion to allow calculation of diffusion coefficients D in cm2/min. The average single-layer D divided by the average double-layer D was 1.3 ± 0.2. Double gloving in the field is therefore also probably more protective than single gloving against DGBE for the four types of disposable nitrile gloves tested.


Assuntos
Etilenoglicóis/química , Luvas Protetoras , Teste de Materiais , Nitrilas , Permeabilidade
20.
Drug Dev Ind Pharm ; 46(6): 910-915, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32339003

RESUMO

The solubility profile of codeine phosphate in the carbitol and 2-propanol mixtures at 293.2-313.2 K are determined and correlated with some developed cosolvency models. Moreover, the density values of codeine phosphate saturated solutions are also determined and fitted with the Jouyban-Acree model. The model accuracy is investigated by calculating the mean relative deviations (MRDs%). The thermodynamic parameters of codeine phosphate dissolution in the non-aqueous mixtures of carbitol and 2-propanol are also computed by using van't Hoff and Gibbs equations.


Assuntos
1-Propanol , 2-Propanol , Codeína/química , Etilenoglicóis/química , Solubilidade , Solventes , Temperatura , Termodinâmica
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