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1.
Int J Nanomedicine ; 15: 6791-6811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982234

RESUMO

Purpose: Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated. Materials and Methods: The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD+/NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated. Results: The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD+/NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis. Conclusion: E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Epirubicina/administração & dosagem , Indóis/química , Nanopartículas/administração & dosagem , Fototerapia/métodos , Polímeros/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Epirubicina/farmacocinética , Feminino , Humanos , Hipertermia Induzida/métodos , Indóis/administração & dosagem , Lasers , Camundongos Endogâmicos BALB C , NAD/metabolismo , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Polímeros/administração & dosagem , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Temperatura , Distribuição Tecidual , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
2.
AAPS PharmSciTech ; 21(6): 217, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32743738

RESUMO

Currently, there is no specific treatment for acute lung injury (ALI) in clinical practice. In order to efficiently and accurately treat ALI, the advantages of cationic carriers were combined to accelerate the cell uptake. Polycaprolactone-polyethylene glycol carrier (PCL-PEG-COOH, PPC) with good biocompatibility, polycaprolactone-polyethylmethacrylate cationic carrier (PCL-PDMAEMA, PCD), and polycaprolactone-polyethylene glycol carrier connected with high-affinity targeting peptide (Esbp) targeting inflammatory endothelial cells (PCL-PEG-Esbp, PPE) were used to construct the high-molecular polymer micelles (PCD/PPC/PPE). The particle size of the prepared DEX-loaded micelles was 130 ± 4.41 nm, and the Zeta potential was 28.3 ± 0.76 mV. The CMC value of the prepared polymer micelles was 0.643 µg/mL, and it was not easy to depolymerize in the blood circulation. Only about 40% DXM was released from the drug-loaded polymer micelles after 12 h compared with free DXM, indicating that the micelle material had a certain sustained-release performance in vitro release experiments. The safe concentration range of polymer was determined by biocompatibility test. It was recommended that the concentration of polymer micelles should not exceed 0.40 mg/mL to obtain a good compatibility in organisms. The results of cytotoxicity measurement showed that when the content of PCD increased to 50%, the concentration of blank micelles should not exceed 500 µg/mL and the concentration of DXM-loaded micelles should not be higher than 100 µg/mL. It was proved in the cell uptake experiment that the cation carrier of the micelles accelerated the cell uptake. The targeting ability of the targeted micelle group was higher compared with the non-targeted micelle group (P < 0.01, **). Meanwhile, the targeting ability of the non-targeted micelle group was higher compared with the free group (P < 0.001, ***). The targeting ability of the non-targeted micelle group was about 2.30 times and the targeted micelle group was about 3.16 times larger than that of the free group. It was also proved in the in vivo targeting experiments that the targeted micelles had a good targeting ability. The results of in vivo imaging of mice showed that the DXM of the micelle group gathered more in the lungs, and the micelle group had a better targeting ability compared with the free DID group. The order of lung targeting intensity was targeted micelles > non-targeted micelles >> free DID group. The targeting ability of polypeptide Esbp to ALI was confirmed. In conclusion, the prepared PCD/PPC/PPE polymer micelles had obvious in vitro and in vivo targeting ability and good biocompatibility. They could be used as a new targeted delivery system for the treatment of ALI in the future.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Inflamação/tratamento farmacológico , Micelas , Polímeros/administração & dosagem , Animais , Dexametasona/administração & dosagem , Portadores de Fármacos/química , Humanos , Camundongos , Tamanho da Partícula , Polímeros/química , Polímeros/uso terapêutico
3.
Crit Rev Ther Drug Carrier Syst ; 37(3): 271-303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749140

RESUMO

Nanotechnology has made great contributions in the development of materials with potential application in different areas, especially in the pharmaceutical sector, where nano-systems are being intensely studied for controlled drug release. These innovative systems are composed of structures such as nanoparticles, nanoemulsions, and cyclodextrins, with the aim of promoting enhanced bioavailability of bioactive molecules. Among these nanocarriers, vesicles such as liposomes and polymersomes are considered to be promising alternatives in delivering hydrophilic and lipophilic drugs. They have different classifications according to their composition, among which are hybrid vesicles, which unlike liposomes are composed of both lipids and polymers. These vesicular systems stand out for combining the advantages of both components, overcoming the limitations of traditional systems imposed by low stability and premature release of the encapsulated active substance. The polymers applied in hybrid vesicles can make up the membrane structure itself or be employed to coat preformed vesicles. Due to the relevance of these systems, this work covers their characteristics and summarizes recent articles about them in the literature.


Assuntos
Cosméticos/administração & dosagem , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Polímeros/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Cosméticos/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipídeos/química , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/química , Polímeros/química
4.
AAPS PharmSciTech ; 21(5): 184, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632735

RESUMO

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.


Assuntos
Monoterpenos Acíclicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fibromialgia/tratamento farmacológico , Nanocápsulas , Polímeros/administração & dosagem , Monoterpenos Acíclicos/farmacocinética , Monoterpenos Acíclicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula , Solubilidade
5.
AAPS PharmSciTech ; 21(3): 101, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152890

RESUMO

The hydrophobicity of bioactive molecules poses a considerable problem in the pharmaceutical and the food industry. Using food-based protein nanocarriers is one promising way to deliver hydrophobic molecules. These types of protein possess many functional properties such as surface activity, water-binding capacity, emulsification, foaming, gelation, and antioxidant activity, as well as their incorporation in the food industry as ingredients. Besides, they express low toxicity, are less expensive compared to synthetic polymers, and are biodegradable. This review aims to give a brief overview of the recent studies done using food proteins as colloidal delivery systems for hydrophobic and poorly soluble compounds.


Assuntos
Proteínas na Dieta/administração & dosagem , Proteínas na Dieta/química , Sistemas de Liberação de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Sistemas de Liberação de Medicamentos/tendências , Géis , Humanos , Polímeros/administração & dosagem , Polímeros/química , Solubilidade , Água
7.
Chem Commun (Camb) ; 56(16): 2415-2418, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31994584
8.
AAPS PharmSciTech ; 21(3): 78, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970547

RESUMO

Protein drugs were considered to be the first choice to treat many human diseases, but their clinical application was usually limited by their short half-life and lack of validated targeted therapy. Here, a series of folate-functionalized poly(ethylene glycol)-b-(poly(2-aminoethyl-L-glutamate)-g-poly(L-glutamic acid))s (FA-PEG-b-(PELG-g-PLGA)s) were designed as tumor-targeted carriers for cationic protein delivery. Compared with traditional copolymers consisting of PEG and linear charged hydrophilic blocks, FA-PEG-b-(PELG-g-PLGA) with brush-like polyelectrolyte segments were beneficial to improving their electrostatic interactions with loading protein molecules, thus increasing drug-loading stability and protecting encapsulated proteins from degradation. The designed polymer brushes could efficiently encapsulate cytochrome C (CytC), a cationic model protein, to form polyion complex (PIC) micelles with an average particle size of approximately 200 nm. An in vitro drug release study showed that the drug-loading stability of the formed PIC micelles was largely improved. The functionalization of the block copolymer carriers with a targeting folate group enhanced the tumor cell growth inhibition and total apoptotic rates induced by CytC. Our results shed light on the unique advantages of brush-like polymer carriers in delivering cationic proteins, and the poly(L-glutamic acid)-based linear-brush diblock copolymers could be applied as a versatile delivery platform for molecular targeting in cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ácido Glutâmico/síntese química , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Proteínas/síntese química , Animais , Cátions , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/metabolismo , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Células NIH 3T3 , Tamanho da Partícula , Poliésteres/administração & dosagem , Poliésteres/metabolismo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/metabolismo , Proteínas/administração & dosagem , Proteínas/metabolismo
10.
Postgrad Med ; 132(2): 176-183, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31971043

RESUMO

Objective: Patiromer is a sodium-free, non-absorbed, potassium (K+) binder approved for the treatment of hyperkalemia (HK). Among US Veterans with HK, this retrospective, observational cohort study evaluated patiromer utilization, RAASi continuation, and K+ concentration change following patiromer initiation.Methods: Using data from the Veterans Affairs Corporate Data Warehouse, Veterans with HK (K+ ≥5.1 mmol/L) were included upon patiromer initiation (index date) during the study period (1/2016-8/2018). All patients had heart failure (HF), diabetes, or chronic kidney disease (CKD). Patients with end-stage renal disease were excluded. The following outcomes were assessed within 6-months post-patiromer initiation: patiromer utilization (using proportion of days covered); K+ concentration change (pre- vs post-initiation); and RAASi continuation.Results: 288 Veterans with HK were included. Baseline characteristics were: median age 70 years, African-American race 24%, diabetes 83%, HF 32%, CKD 95%, and median K+ concentration 5.7 mmol/L. At 1, 3, and 6 months post-index, the median patiromer PDC was 100%, 66%, and 44%, respectively. K+ concentration reductions post-patiromer initiation were, on average, - 1.0 mmol/L (P < 0.001). At 3-6 months, 71% of patiromer initiators had K+ <5.1 mmol/L and 95% had K+ <5.5 mmol/L. RAASi therapy was continued in >80%-90% of patiromer-treated patients.Conclusions: The real-world utilization results suggest patiromer is used for the chronic management of HK. Clinically relevant K+ concentration reductions were observed at all study time points. The successful management of HK may have contributed to the observed high rate of RAASi therapy continuation. Further research is warranted to corroborate and extend these findings.


Assuntos
Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/epidemiologia , Polímeros/uso terapêutico , Fatores Etários , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Grupos de Populações Continentais , Diabetes Mellitus/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Polímeros/administração & dosagem , Potássio/sangue , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Estados Unidos , Veteranos
11.
Nutrients ; 12(1)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963440

RESUMO

Melanoidins are the final Maillard reaction products (protein-carbohydrate complexes) produced in food by prolonged and intense heating. We assessed the impact of the consumption of melanoidins from barley malts on gut microbiota. Seventy-five mice were assigned into five groups, where the control group consumed a non-melanoidin malt diet, and other groups received melanoidin-rich malts in increments of 25% up to 100% melanoidin malts. Feces were sampled at days 0, 1, 2, 3, 7, 14, and 21 and the microbiota was determined using V4 bacterial 16S rRNA amplicon sequencing and short-chain fatty acids (SCFA) by gas chromatography. Increased melanoidins was found to result in significantly divergent gut microbiota profiles and supported sustained SCFA production. The relative abundance of Dorea, Oscillibacter, and Alisitpes were decreased, while Lactobacillus, Parasutterella, Akkermansia, Bifidobacterium, and Barnesiella increased. Bifidobacterium spp. and Akkermansia spp. were significantly increased in mice consuming the highest melanoidin amounts, suggesting remarkable prebiotic potential.


Assuntos
Bactérias/metabolismo , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal , Produtos Finais de Glicação Avançada/administração & dosagem , Hordeum , Polímeros/administração & dosagem , Prebióticos/administração & dosagem , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bactérias/classificação , Ingestão de Alimentos , Fezes/microbiologia , Produtos Finais de Glicação Avançada/metabolismo , Temperatura Alta , Reação de Maillard , Masculino , Camundongos Endogâmicos C57BL , Polímeros/metabolismo , Ganho de Peso
12.
Biomater Sci ; 8(6): 1604-1614, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-31967113

RESUMO

Autografts are still regarded as the gold standard treatment for bone defects but they require additional surgery that causes pain for the patient. Thus, alternatives that can substitute for grafts are required. In the present study, a novel poly-GLP-1 molecule was developed using a polymeric pro-drug strategy which was found to accelerate bone healing in a mouse femoral defect model. Furthermore, the poly-GLP-1 molecule induced osteogenesis and inhibited adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). The results demonstrate that poly-GLP-1 promoted M2 polarization of bone marrow-derived macrophages (BMDMs) and increased the levels of TGF-ß1 in the bone marrow, resulting in the migration of an increased number of CD29 + Sca-1 + BMSCs to the bone surface. Finally, we found that poly-GLP-1 facilitated the migration of BMSCs due to transduction of the Smad2 signaling pathway, causing increased numbers of CD31 + Endomucin + endothelial cells in bone marrow that promoted bone formation. These results support poly-GLP-1 as a potential bone-healing agent and suggest that it may play a promising role in the clinical treatment of fracture repair.


Assuntos
Fêmur/lesões , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Células-Tronco Mesenquimais/citologia , Osteogênese , Polímeros/administração & dosagem , Adipogenia/efeitos dos fármacos , Animais , Polaridade Celular/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Polímeros/química , Polímeros/farmacologia , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
13.
Carbohydr Polym ; 227: 115333, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590864

RESUMO

The gold nanoparticles surface was modified by thioglycolic acid ligand and their surface was coated by the chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) copolymer. The cisplatin anticancer drug was loaded into the synthesized nanocarriers and its performance was investigated for the treatment of MCF-7 breast cancer cells in vitro. The synthesized nanoparticles were characterized using FTIR, DLS, TEM, SEM, EDX and TGA analysis. The lower critical solution temperature (LCST) of PNVCL/chitosan and PNVCL/chitosan coated gold nanoparticles were found to be 38 and 39 °C, respectively. The cisplatin loading efficiency, cisplatin release from nanoparticles at different temperatures and pH values as well as the pharmacokinetic studies were examined. The maximum cisplatin release from nanoparticles was achieved at T > LCST (42 °C) and pH of 5. The Korsemeyer-Peppas model was best described the cisplatin release from nanoparticles. The maximum MCF cell death was found to be 92% using cisplatin loaded-gold/TGA/chitosan-g-PNVCL nanoparticles under an induction heating system.


Assuntos
Antineoplásicos , Caprolactama/análogos & derivados , Quitosana , Cisplatino , Ouro , Nanopartículas Metálicas , Polímeros , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Caprolactama/administração & dosagem , Caprolactama/química , Caprolactama/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Quitosana/química , Quitosana/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/química , Cisplatino/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Ouro/administração & dosagem , Ouro/química , Humanos , Células MCF-7 , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacocinética
14.
Colloids Surf B Biointerfaces ; 185: 110578, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678812

RESUMO

Pseudo-binary mixtures of different glycolipids, four different rhamnolipids (RL) and an alkyl polyglucoside (APG), with poly(diallyl-dimethylammonium chloride) (PDADMAC) have been studied in relation to their adsorption onto negatively charged surfaces to shed light on the impact of the molecular structure of surfactants from natural sources (instead of synthetic surfactant, such as sodium laureth sulfate) on the adsorption of hair-conditioning polymers. For this purpose, the self-assembly of such mixtures in aqueous solution and their adsorption onto negatively charged surfaces mimicking the negative charge of damaged hair fibres have been studied combining experiments and self-consistent field (SCF) calculations. The results show that the specific physico-chemical properties of the surfactants (charge, number of sugar rings present in surfactant structure and length of the hydrocarbon length) play a main role in the control of the adsorption process, with the adsorption efficiency and hydration being improved in relation to conventional sulfate-based systems for mixtures of PDADMAC and glycolipids with the shortest alkyl chains. SCF calculations and Energy Dispersive X-Ray Spectroscopy (EDS) analysis on real hair confirmed such observations. The results allow one to assume that the characteristic of the surfactants, especially rhamnolipids, conditions positively the adsorption potential of polyelectrolytes in these model systems. This study provides important insights on the mechanisms underlying the performance of more complex but eco-friendly washing formulations.


Assuntos
Glicolipídeos/química , Cabelo/efeitos dos fármacos , Teste de Materiais , Polietilenos/química , Polímeros/química , Compostos de Amônio Quaternário/química , Tensoativos/química , Adsorção , Biomimética , Glicolipídeos/metabolismo , Cabelo/química , Humanos , Modelos Moleculares , Estrutura Molecular , Polímeros/administração & dosagem , Tensoativos/metabolismo
15.
Toxicol Appl Pharmacol ; 386: 114833, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756429

RESUMO

One of the main problems for the development of pulmonary formulations is the low availability of approved excipients. Polyglycerol esters of fatty acids (PGFA) are promising molecules for acting as excipient for formulation development and drug delivery to the lung. However, their biocompatibility in the deep lung has not been studied so far. Main exposed cells include alveolar epithelial cells and alveolar macrophages. Due to the poor water-solubility of PGFAs, the exposure of alveolar macrophages is expected to be much higher than that of epithelial cells. In this study, two PGFAs and their mixture were tested regarding cytotoxicity to epithelial cells and cytotoxicity and functional impairment of macrophages. Cytotoxicity was assessed by dehydrogenase activity and lactate dehydrogenase release. Lysosome function, phospholipid accumulation, phagocytosis, nitric oxide production, and cytokine release were used to evaluate macrophage function. Cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/ml accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs in concentrations up to 1 mg/ml can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.


Assuntos
Excipientes/farmacologia , Excipientes/toxicidade , Ácidos Graxos/toxicidade , Glicerol/toxicidade , Polímeros/toxicidade , Células A549 , Administração por Inalação , Proteínas Aviárias/metabolismo , Citocinas/metabolismo , Excipientes/administração & dosagem , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Glicerol/administração & dosagem , Glicerol/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Polímeros/administração & dosagem , Polímeros/farmacologia , Alvéolos Pulmonares/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Testes de Toxicidade
16.
Curr Opin Gastroenterol ; 36(2): 147-154, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31850930

RESUMO

PURPOSE OF REVIEW: Fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) dietary restriction ameliorates irritable bowel syndrome (IBS) symptoms; however, not all individuals with IBS respond. Given the gut microbiome's role in carbohydrate fermentation, investigators have evaluated whether the gut microbiome may predict low FODMAP diet efficacy. RECENT FINDINGS: Gut microbiome fermentation, even to the same carbohydrate, is not uniform across all individuals with several factors (e.g. composition) playing a role. In both children and adults with IBS, studies are emerging suggesting the gut microbiome may predict low FODMAP diet efficacy. However, there is significant heterogeneity in the approaches (study population, microbiome assessment methods, statistical techniques, etc.) used amongst these studies. SUMMARY: The gut microbiome holds promise as a predictor of low FODMAP diet efficacy. However, further investigation using standardized approaches to evaluate the microbiome while concomitantly assessing other potential predictors are needed to more rigorously evaluate this area.


Assuntos
Dieta com Restrição de Carboidratos/métodos , Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/dietoterapia , Monossacarídeos/administração & dosagem , Oligossacarídeos/administração & dosagem , Polímeros/administração & dosagem , Dissacarídeos/administração & dosagem , Dissacarídeos/metabolismo , Fermentação , Gastroenteropatias/dietoterapia , Gastroenteropatias/metabolismo , Gastroenteropatias/fisiopatologia , Humanos , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Monossacarídeos/metabolismo , Oligossacarídeos/metabolismo , Polímeros/metabolismo , Resultado do Tratamento
17.
Int J Pharm ; 575: 118898, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31846730

RESUMO

Although RNA interference (RNAi) technology shows great potential in cancer treatment, the tumor target delivery and sufficient cytosolic transport of RNAi agents are still the main obstacles for its clinical applications. Herein, we report a functional supramolecular self-assembled nanoparticle vector for RNAi agent loading and tumor target therapy. Molecular block adamantane-grafted poly(ethylene glycol) (Ad-PEG) was modified with epidermal growth factor receptor (EGFR)-specific binding ligand GE11 or pH-sensitive fusogenic peptide GALA and then used for self-assembly with cyclodextrin-grafted branched polyethylenimine (CD-PEI), adamantane-grafted polyamidoamine dendrimer (Ad-PAMAM), and plasmid DNA containing a small hairpin RNA expression cassette against vascular endothelial growth factor (VEGF) into functional DNA-loaded supramolecular nanoparticles (GE11&GALA-pshVEGF@SNPs) based on molecular recognition and charge interaction. These functional peptides facilitated the target cell binding, internalization, and endosomal escape of GE11&GALA-pshVEGF@SNPs, resulting in increased reporter gene expression and efficient targeted gene silencing. The systemic delivery of the GE11&GALA-pshVEGF@SNPs can efficiently downregulate the intratumoral VEGF protein levels, reduce blood vessel formation, and significantly inhibit A549 xenograft tumor growth. These results reveal the potential of these multifunctional self-assembled nanoparticles as a nucleic acid drug delivery system for the treatment of lung cancer.


Assuntos
DNA/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias/terapia , Neovascularização Patológica/tratamento farmacológico , Peptídeos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Células A549 , Adamantano/administração & dosagem , Animais , Feminino , Inativação Gênica , Humanos , Camundongos Nus , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Plasmídeos , Polímeros/administração & dosagem , Carga Tumoral/efeitos dos fármacos
18.
Int J Nanomedicine ; 14: 8647-8663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31806962

RESUMO

Background: Chemo-photothermal therapy has attracted intensive attention because of its low side effects and better therapeutic efficiency. Although many photothermal agents have been loaded with chemotherapeutic drugs for chemo-photothermal therapy, their applications are limited by complex synthetic protocols and long-term safety. Therefore, there is significant clinical value in the development of a simple system of biocompatible and biodegradable photothermal nanomaterials with high payloads of chemotherapeutic drugs for chemo-photothermal synergistic therapy. Materials and methods: In this study, PEG-modified polydopamine nanoparticles with mesoporous structure (MPDA-PEG) were successfully obtained by an emulsion-induced interface assembly strategy. Subsequently, paclitaxel (PTX) dissolved in acetone was loaded into the mesoporous channels of MPDA-PEG nanoparticles by solution absorption method. A PTX-loaded MPDA-PEG (MPDA-PEG-PTX) nanoplatform for combination of photothermal therapy (PTT) and chemotherapy was developed. Results: The synthesized MPDA-PEG nanoparticles had a great photothermal effect under near-infrared (NIR) laser irradiation and exhibited an enhanced photothermal effect with the increase of particle size. Meanwhile, MPDA-PEG nanoparticles also had a high payload of PTX, and the PTX release could be greatly accelerated by elevated temperature from photothermal effect. In MTT cytotoxicity assay, A549 cells incubated with MPDA-PEG-PTX under NIR laser irradiation (PTT + chemotherapy group) exhibited better therapeutic effect than single chemotherapy (MPDA-PEG-PTX group) and PTT (MPDA-PEG + Laser group). The synergistic therapeutic effect of MPDA-PEG-PTX with NIR laser irradiation in vivo was further investigated under the guidance of photoacoustic imaging (PAI), tumors of nude mice treated with MPDA-PEG-PTX with NIR laser irradiation were completely eliminated with minimal side effect. Conclusion: The MPDA-PEG-PTX nanoplatform is a simple and effective platform which can completely inhibit tumor growth with minimal side effects under NIR irradiation, and it exhibits better therapeutic effect than single chemotherapy and PTT.


Assuntos
Indóis/farmacologia , Nanopartículas/química , Paclitaxel/farmacologia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Polímeros/farmacologia , Células A549 , Animais , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Indóis/administração & dosagem , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Tamanho da Partícula , Polímeros/administração & dosagem , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Nanobiotechnology ; 17(1): 113, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699100

RESUMO

BACKGROUND: Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity. RESULTS: In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(L-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 µg/mL) and better therapeutic efficacy than that of free EPI in vivo. CONCLUSIONS: This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Epirubicina/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/uso terapêutico , Liberação Controlada de Fármacos , Epirubicina/farmacocinética , Epirubicina/uso terapêutico , Transferência Ressonante de Energia de Fluorescência , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/administração & dosagem , Polímeros/farmacocinética , Polímeros/uso terapêutico
20.
Int J Pharm ; 572: 118731, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31669213

RESUMO

Most pathogens enter the body through mucosal surfaces. Therefore, vaccination through the mucosal route can greatly enhance the mucosal immune response. Vaccination via the mucosal surface is the most effective way to trigger a protective mucosal immune response, but the vast majority of vaccines used are administered by injection. Strategies to enhance the mucosal immunity have been developed by using vaccine adjuvants, delivery systems, bacterial or viral vectors, and DNA vaccines. Appropriate vaccine adjuvants and drug delivery systems can improve the immunogenicity of antigens, induce a stronger immune response, and reduce the vaccine dose and production cost. In recent years, many studies have focused on finding safe and effective vaccine adjuvants and drug delivery systems to formulate the mucosal vaccines for solving the above problems. Great progress has also been made in vaccine adjuvants and drug delivery systems based on biodegradable polymer nanoparticles. In this paper, the research progress of the mucosal vaccine and its related adjuvants and drug delivery systems in recent years was reviewed, and the application of polymers as adjuvants and drug delivery system in vaccine was prospected. This review provides a fundamental knowledge for the application of biodegradable polymer nanoparticles as adjuvants and carriers in mucosal vaccines and shows great application prospects.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Membrana Mucosa/imunologia , Nanopartículas/administração & dosagem , Polímeros/administração & dosagem , Vacinas/administração & dosagem , Animais , Humanos , Vacinação
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