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1.
Nanoscale ; 11(39): 18209-18223, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31560010

RESUMO

Rheumatoid arthritis (RA) is a degenerative joint disease caused by autoimmunity; for the effective treatment of RA while avoiding the side effects of conventional drugs, we have proposed a new therapeutic strategy to eliminate the inflammatory response in RA by regulating the immune system that promotes the transformation of M1-type macrophages to M2-type macrophages. Herein, we designed and synthesized a core-shell nanocomposite (QRu-PLGA-RES-DS NPs), which showed an effective therapeutic effect on RA by accurately inducing the polarization of M2 macrophages. In this system, the quadrilateral ruthenium nanoparticles (QRuNPs) with a photothermal effect were utilized as a core and the thermosensitive molecular poly (lactic-co-glycolic acid) (PLGA) modified with the targeted molecule dextran sulfate (DS) was employed as a shell. Then, the nanocarrier QRu-PLGA-DS NPs effectively improved the water solubility and targeting of resveratrol (RES) through self-assembly. Therefore, the QRu-PLGA-RES-DS NPs significantly enhanced the ability of RES to reverse the M1 type macrophages to the M2 type macrophages through an accurate release. In vivo experiments further demonstrated that the QRu-PLGA-RES-DS NPs could effectively accumulate in the lesion area with an exogenous stimulus, and this significantly enhanced the transformation of the M2 type macrophages and decreased the recruitment of the M1 type macrophages. Furthermore, the QRu-PLGA-RES-DS NPs effectively treated RA by eliminating the inflammatory response; in addition, photoacoustic imaging (PA) of the QRu NPs provided image guidance for the distribution and analysis of nanomedicine in inflammatory tissues. Hence, this therapeutic strategy promotes the biological applications of Ru-based nanoparticles in disease treatment.


Assuntos
Hipertermia Induzida , Macrófagos/metabolismo , Nanocompostos , Fototerapia , Resveratrol , Febre Reumática/terapia , Animais , Células Endoteliais da Veia Umbilical Humana , Humanos , Macrófagos/patologia , Camundongos , Nanocompostos/química , Nanocompostos/uso terapêutico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Células RAW 264.7 , Resveratrol/farmacocinética , Resveratrol/farmacologia , Febre Reumática/metabolismo , Febre Reumática/patologia , Rutênio/química , Rutênio/farmacocinética , Rutênio/farmacologia
3.
Microsurgery ; 39(5): 395-399, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30562848

RESUMO

BACKGROUND: In this study, we evaluated the clinical efficacy of a biodegradable nerve conduit constructed of polyglycolic acid (PGA) tube with external and internal collagen scaffolding for digital nerve repair. PATIENTS AND METHODS: A multi-center registry study was conducted in 11 locations between July 2013 and May 2016. Multiple mechanisms of injury included clean-cut (12 patients), crush (5 patients), and avulsion (3 patients) types of injuries. These patients underwent nerve repair with a biodegradable nerve conduit, with 9 patients having a primary repair and 11 patients having delayed repair. Average nerve gap was 16.7 mm (range: 1-50 mm). An average of 13 months follow-up (range: 12-15 months) was available including sensory assessments. RESULTS: Improved s2PD was found with less severe injury as in clean-cut (7.5 ± 1.5 mm), which was statistically significant in comparison to those in crush (9.8 ± 1.9 mm, P = .0384) and in avulsion (10.7 ± 4.7 mm, P = .0013) type injuries. A meaningful recovery (S3+ or S4) was observed in 90% of the 20 digital nerve repairs with a biodegradable nerve conduit of PGA with external and internal collagen scaffolding. Avulsion injuries had significantly lower levels of meaningful recovery (67%) in comparison to those of clean-cut (P = .0291) and crush (P = .0486) types of injury. No adverse effects were reported postoperatively. CONCLUSION: These results indicate that a biodegradable nerve conduit of PGA with external and internal collagen scaffolding is suitable for digital nerve repair of short nerve gaps with high levels of sensory recovery as measured by two-point discrimination.


Assuntos
Implantes Absorvíveis , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/cirurgia , Ácido Poliglicólico/farmacologia , Sistema de Registros , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Traumatismos dos Dedos/cirurgia , Dedos/inervação , Dedos/cirurgia , Seguimentos , Força da Mão/fisiologia , Humanos , Escala de Gravidade do Ferimento , Japão , Masculino , Pessoa de Meia-Idade , Traumatismos dos Nervos Periféricos/diagnóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Tecidos Suporte , Cicatrização/fisiologia , Adulto Jovem
4.
Artif Cells Nanomed Biotechnol ; 46(sup3): S481-S491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30299174

RESUMO

In our study, we have established a novel liquid-driven co-flow focusing (LDCF) process to fabricate curcumin (CUR)-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (CPMs). LDCF-CPMs of size 20.26 ± 2.37 µm have high encapsulation efficiency (>70%) and were intended for application in ovarian cancer by intraperitoneal (IP) administration. LDCF-CPMs have smooth surface with narrow size distribution and a core-shell structured verified by confocal microscopy which can be precisely controlled by changing the flow rates of focusing, outer and inner phases. The LDCF-CPMs reveal the physiochemical stability with sustained release profile corresponding to 95% CUR release over a period of 14 days in an in vitro release medium. Moreover, LDCF-CPMs were testified for cytotoxicity against SKOV-3 ovarian cancer cell lines and peritoneal delivery advantages by animal experiments. The pharmacokinetics of LDCF-CPMs in rats following IP injection shows slow systemic absorption with mean residence time (MRT) of 13.54 h in comparison with 9.82 and 6.74 h for SE-CPMs and free CUR, respectively. In addition, IP delivery of CUR can expose the ovarian tumour to higher concentration for a longer duration by programming the thickness of the shell. The study provides compelling evidence for LDCF-CPMs having high therapeutic opportunity in the treatment of peritoneal cancers, such as ovarian, that reside in the peritoneal cavity.


Assuntos
Antineoplásicos Fitogênicos , Curcumina , Nanopartículas , Neoplasias Ovarianas , Ácido Poliglicólico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Ratos , Ratos Wistar , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Acta Biomater ; 81: 208-218, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30267881

RESUMO

Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. STATEMENT OF SIGNIFICANCE: The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.


Assuntos
Citotoxinas , Portadores de Fármacos , Receptores de Hialuronatos/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias , Ácido Poliglicólico , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Nanopartículas , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia
6.
Wound Repair Regen ; 26(6): 446-455, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30118577

RESUMO

Adipose-derived stem cells (ADSCs) and the stromal vascular fraction (SVF) promote nerve regeneration. Biodegradable nerve conduits are used to treat peripheral nerve injuries, but their efficiencies are lower than those of autologous nerve grafts. This study developed biodegradable nerve conduits containing ADSCs and SVF and evaluated their facial nerve regenerating abilities in a rat model with a 7-mm nerve defect. SVF and ADSCs were individually poured into nerve conduits with polyglycolic acid-type I collagen as a scaffold (ADSCs and SVF groups). The conduits were grafted on to the nerve defects. As the control, the defect was bridged with polyglycolic acid-collagen nerve conduits without cells. At 13 weeks, after transplantation, the regenerated nerves were evaluated physiologically and histologically. The compound muscle action potential of the SVF group was significantly higher in amplitude than that of the control group. Electron microscopy showed that the axon diameter of the SVF group was the largest, followed by the ADSC group and control group with significant differences among them. The SVF group had the largest fiber diameter, followed by the ADSC group and control group with significant differences among them. The ADSC group had the highest myelin thickness, followed by the SVF group and control group with significant differences among them. Identical excellent promoting effects on nerve regeneration were observed in both the ADSC and SVF groups. Using SVF in conduits was more practical than using ADSCs because only the enzymatic process was required to prepare SVF, indicating that SVF could be more suitable to induce nerve regeneration.


Assuntos
Tecido Adiposo/citologia , Colágeno/farmacologia , Nervo Facial/fisiopatologia , Regeneração Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/terapia , Ácido Poliglicólico/farmacologia , Células-Tronco/citologia , Adipócitos/citologia , Adipócitos/transplante , Tecido Adiposo/transplante , Animais , Modelos Animais de Doenças , Regeneração Nervosa/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/fisiopatologia , Ratos , Recuperação de Função Fisiológica/fisiologia , Células-Tronco/efeitos dos fármacos
7.
J Mater Sci Mater Med ; 29(8): 133, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30094505

RESUMO

Chronic wounds and related infections cause physical and psychological distress in patients, increased mortality, disability and high health care costs. The healing process can be delayed by several factors and in particular by the risk of infections, which can be further complicated by the increasing number of antibiotic-resistant microorganisms. New approaches in wounds management have been encouraged, aiming at preventing infections and improving wound healing. In this scenario, silver has emerged as an ideal antimicrobial agent due to its recognized efficacy against bacteria, viruses and fungi. Moreover, silk and in particular silk sericin from Bombyx mori has demonstrated excellent biological properties and can be considered a good candidate for skin tissue engineering. In this study absorbable PLGA sutures were functionalized with silk sericin and, then, they were treated with silver through an in situ photochemical deposition technology in order to develop an antibacterial and regenerative biomedical device. Morphological analysis was performed by Scanning Electron Microscopy and Energy Dispersive X-Ray Spectroscopy (SEM-EDX) in order to evaluate the presence and distribution of silver deposited on the sutures. The stability and durability of the sericin/silver coatings were tested and the results were related to both antibacterial properties and sample degradation. The biological analyses also aimed at studying the biocompatibility and wound healing properties of the device, evaluating the synergistic effect between sericin and silver.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Sericinas/química , Prata/química , Suturas , Animais , Bactérias/efeitos dos fármacos , Materiais Biocompatíveis , Fibroblastos/efeitos dos fármacos , Regeneração Tecidual Guiada , Ácido Láctico/química , Ácido Láctico/farmacologia , Microscopia Eletrônica de Varredura/métodos , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espectrometria por Raios X/métodos
8.
Int J Mol Sci ; 19(7)2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30011926

RESUMO

Cell responses depend on the stimuli received by the surrounding extracellular environment, which provides the cues required for adhesion, orientation, proliferation, and differentiation at the micro and the nano scales. In this study, discontinuous microcones on silicon (Si) and continuous microgrooves on polyethylene terephthalate (PET) substrates were fabricated via ultrashort pulsed laser irradiation at various fluences, resulting in microstructures with different magnitudes of roughness and varying geometrical characteristics. The topographical models attained were specifically developed to imitate the guidance and alignment of Schwann cells for the oriented axonal regrowth that occurs in nerve regeneration. At the same time, positive replicas of the silicon microstructures were successfully reproduced via soft lithography on the biodegradable polymer poly(lactide-co-glycolide) (PLGA). The anisotropic continuous (PET) and discontinuous (PLGA replicas) microstructured polymeric substrates were assessed in terms of their influence on Schwann cell responses. It is shown that the micropatterned substrates enable control over cellular adhesion, proliferation, and orientation, and are thus useful to engineer cell alignment in vitro. This property is potentially useful in the fields of neural tissue engineering and for dynamic microenvironment systems that simulate in vivo conditions.


Assuntos
Materiais Biocompatíveis/química , Ácido Láctico/química , Polietilenotereftalatos/química , Ácido Poliglicólico/química , Células de Schwann/citologia , Animais , Axônios/efeitos dos fármacos , Axônios/fisiologia , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Ácido Láctico/farmacologia , Lasers , Camundongos , Regeneração Nervosa/efeitos dos fármacos , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células de Schwann/fisiologia , Silício/química , Propriedades de Superfície , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
9.
Int J Biol Macromol ; 118(Pt A): 932-937, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29966670

RESUMO

In present study, HEP was successfully encapsulated into the Poly (lactic-coglycolicacid) (PLGA) to constitute the HEP-PLGA. The effects of three independent factors (the proper range of ratio of organic phase (o) to internal water phase (w1) (X1), ratio of external water phase (w2) to the primary emulsion (PE) (X2), and the concentration of PLGA (X3) on the extraction yield of encapsulation efficiency (EE) from the HEP was optimized using response surface methodology. The optimal extraction conditions for HEP-PLGA were determined as follows: X1: 8:1, X2: 7:1 and X3: 20 mg·mL-1. Under these optimal conditions, the mean experimental EE 90.86 ±â€¯0.576% was corresponded well with the predicted value of 91.81%. In addition, to investigate the transport properties of HEP and HEP-PLGA using a Caco-2 cell monolayer, and study the roles of the efflux transporters (P-gp) during the transport process. These results suggested that HEP can be absorbed more efficiently when encapsulated within the PLGA. These findings highlight the potential to the application of HEP in the formulation of functional foods. These results provide strategies in designing high absorbed polysaccharides with bioactive benefits.


Assuntos
Basidiomycota/química , Polissacarídeos Fúngicos , Ácido Láctico , Nanopartículas/química , Ácido Poliglicólico , Células CACO-2 , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacocinética , Polissacarídeos Fúngicos/farmacologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
10.
Mater Sci Eng C Mater Biol Appl ; 91: 715-726, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033306

RESUMO

Tissue engineering scaffold provide an effective alternative for peripheral nerve repair. Nanofibrous nerve conduits fabricated with various synthetic and natural materials have great potential to support nerve regeneration as a bridge between adjacent ends. The physical, chemical and electrical properties of the scaffolds affect the outcome of nerve regeneration and recovery of function. In this paper, a surface modified, electrically conductive, aligned nanofibrous scaffold composed of poly(lactic-co-glycolic acid) (PLGA) and multi-walled carbon nanotubes (MWCNTs), referred to as L-PC_A was fabricated for nerve regeneration. The morphology, surface chemistry and hydrophilicity of nanofibers were characterized by Scanning Electron Microscopy (SEM), Energy-dispersive X-ray (EDX) and water contact angle, respectively. The mechanical property of the nanofibrous scaffold was also evaluated using a universal materials tester. The effects of these scaffolds on PC12 cell adhesion, proliferation and neuronal differentiation were all evaluated. A hydrophilic surface was created by poly-l-lysine coating, which was able to provide a better environment for cell attachment. Furthermore aligned fibers were proved to be able to guide PC12 cells and DRG neurons growing along the fiber direction and be beneficial for neurite outgrowth. The cellular responses of PC12 cells and DRG neurons on L-PC_A scaffold under electrical stimulation were evaluated by neurofilament proteins expression. As a result, the PC12 cells and DRG neurons stimulated with electrical shock showed longer neurite length, indicating that electrical stimulation with a voltage of 40 mV based on the scaffold with MWCNTs could enhance the neurite extension. Moreover, the cellular response of Schwann cells including cell attachment, proliferation and MBP expression were also enhanced with the synergistic effect of aligned nanofibers and electrical stimulation. In summary, the L-PC_A nanofibrous scaffold supported the cellular response of nerve cells in terms of cell proliferation, differentiation, neurite outgrowth, and myelination in the presence of electrical stimulation, which could be a potential candidate for nerve regeneration application.


Assuntos
Materiais Revestidos Biocompatíveis/farmacologia , Ácido Láctico/farmacologia , Nanofibras/química , Nanotubos de Carbono/química , Neurônios/citologia , Ácido Poliglicólico/farmacologia , Polilisina/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Estimulação Elétrica , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Nanofibras/ultraestrutura , Nanotubos de Carbono/ultraestrutura , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Células de Schwann/citologia , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Estresse Mecânico , Resistência à Tração , Tecidos Suporte/química
11.
ACS Appl Mater Interfaces ; 10(27): 22939-22950, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29924595

RESUMO

There is an urgent demand for wound healing biomaterials because of the increasing frequency of traffic accidents, industrial contingencies, and natural disasters. Borate bioactive glass has potential applications in bone tissue engineering and wound healing; however, its uncontrolled release runs a high risk of rapid degradation and transient biotoxicity. In this study, a novel organic-inorganic dressing of copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) loaded with vitamin E (0-3.0 wt % vitamin E) was fabricated to evaluate its efficiency for angiogenesis in cells and full-thickness skin wounds healing in rodents. In vitro results showed the dressing was an ideal interface for the organic-inorganic mixture and a controlled release system for Cu2+ and vitamin E. Cell culture suggested the ionic dissolution product of the copper-doped and vitamin E-loaded dressing showed the best migration, tubule formation, and vascular endothelial growth factor (VEGF) secretion in human umbilical vein endothelial cells (HUVECs) and higher expression levels of angiogenesis-related genes in fibroblasts in vitro. Furthermore, this dressing also suggested a significant improvement in the epithelialization of wound closure and an obvious enhancement in vessel sprouting and collagen remodeling in vivo. These results indicate that the copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) dressing loaded with vitamin E is effective in stimulating angiogenesis and healing full-thickness skin defects and is a promising wound dressing in the reconstruction of full-thickness skin injury.


Assuntos
Bandagens , Boratos/farmacologia , Cobre/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Vitamina E/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Boratos/química , Boratos/farmacocinética , Linhagem Celular , Cobre/química , Cobre/farmacocinética , Vidro/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Láctico/química , Ácido Láctico/farmacologia , Neovascularização Fisiológica/genética , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Vitamina E/química , Vitamina E/farmacocinética
12.
Int J Pharm ; 547(1-2): 593-601, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-29800740

RESUMO

Oral administration of proteins and peptides still is a challenging task to overcome due to low permeability through absorptive epithelia, degradation and metabolism that lead to poor bioavailability. Attempting to overcome such limitations, an antihypertensive peptide derived from whey protein, with KGYGGVSLPEW sequence, was incorporated for the first time into polymeric nanoparticles. An experimental design was followed in order to optimize drug-loading, association efficiency, mean particle size, zeta-potential and polydispersity index of a formulation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles as carriers for bioactive peptides. In sequence, peptide-loaded PLGA nanoparticles were incorporated in a guar-gum film matrix, resulting in a combined delivery system aiming to promote slow release and permeation across buccal epithelium. Neither PLGA nanoparticles, guar-gum films nor the conjugation of PLGA nanoparticles and guar-gum films (GfNp) significantly compromised in vitro TR146 human buccal carcinoma cell line viability after 12 h contact, as assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide reduction assay (MTT). In vitro release assay for developed formulations allowed to conclude that the combination of orodispersible film and nanoparticles granted a slower release of AhP when compared with PLGA or guar-gum films alone or with control. GfNp offered more effective, synergistic, in vitro permeation of TR146 cell multilayer in comparison with guar-gum films or PLGA nanoparticles alone. The combination of PLGA nanoparticles with guar-gum films represent a suitable alternative to conventional per os delivery systems, leading to an increased buccal permeability of carried antihypertensive peptide.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/farmacologia , Portadores de Fármacos/farmacologia , Mucosa Bucal/metabolismo , Absorção pela Mucosa Oral/efeitos dos fármacos , Administração Bucal , Inibidores da Enzima Conversora de Angiotensina/química , Animais , Anti-Hipertensivos/química , Disponibilidade Biológica , Bovinos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Células Epiteliais , Galactanos/química , Galactanos/farmacologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacologia , Mananas/química , Mananas/farmacologia , Mucosa Bucal/citologia , Nanopartículas/química , Peptídeos/administração & dosagem , Peptídeos/química , Permeabilidade , Gomas Vegetais/química , Gomas Vegetais/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Língua , Proteínas do Soro do Leite/química
13.
J Agric Food Chem ; 66(24): 6196-6204, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29799193

RESUMO

In the present study, the antigenotoxic activity of poly(d,l-lactic- co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with caffeic acid phenethyl ester (CAPE) was investigated in comparison to free CAPE using the Ames Salmonella/microsome assay. Additionally, to elucidate the impacts of the type of solvent effect on antigenotoxic activity, the following systems were tested: CAPE in water (poor solvent), ethyl alcohol (good solvent), and PLGA NPs (unknown). The effect of the NP system on solubility was investigated for the first time by assessing the antigenotoxic potential. In this study, the CAPE/PLGA NPs were synthesized using an oil-in-water (o/w) single-emulsion solvent evaporation method with an average size of 206.2 ± 1.2 nm, ζ potential of -19.8 ± 2.5 mV, encapsulation efficiency of 87.2 ± 2.5%, and drug loading of 53.3 ± 1.8%. According to the results of the antigenotoxic activity, the highest antimutagenic activity in both applied strains was found for CAPE in ethanol, and the lowest activity was detected for CAPE in water. Our study has shown that NP systems exhibit high antigenotoxic activity, which is similar to the results of CAPE dissolved in ethanol. These results have shown that NP systems increase biological activity of hydrophobic substances by increasing their solubility and that the use of PLGA instead of organic solvents in drug production may provide an increase in their medical utility.


Assuntos
Antimutagênicos/farmacologia , Ácidos Cafeicos/farmacologia , Ácido Láctico/farmacologia , Mutagênicos/toxicidade , Nanopartículas/química , Ácido Poliglicólico/farmacologia , Salmonella/efeitos dos fármacos , Antimutagênicos/química , Ácidos Cafeicos/química , Ésteres/química , Ácido Láctico/química , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Mutação/efeitos dos fármacos , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Salmonella/genética
14.
Int J Biol Macromol ; 116: 648-663, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29723623

RESUMO

PURPOSE: Enhancing the ocular hypotensive effect of forskolin (FK) by means of biodegradable chitosan (CS) coated poly lactic-co-glycolic acid (PLGA) nanoparticles (NP's). METHODS: One step emulsion-sonication process was employed for the formulation of CS-PLGA NP's with optimization being carried out by employing a four factor four level Box Behnken Design. The physical and spectral characterization, drug release, permeation, confocal and ocular tolerance studies (ex-vivo &in vivo) were performed. The corneal retention was assessed by gamma scintigraphic analysis and dexamethasone induced glaucamotous rabbit's intraocular pressure (IOP) was measured by means of Schiotz tonometer. RESULTS AND DISCUSSION: Particle size of optimized CS-PLGA NP's was found as 201.56 ±â€¯10.92 nm with a good PDI and positive zeta potential value. Entrapment efficiency and drug loading were found to be 72.32 ±â€¯1.12% and 28.39 ±â€¯1.67% respectively. Spectral characterization confirmed the purity and encapsulation of the drug within polymeric system. Sustained drug release and enhanced permeation profile was observed with maximum depth penetration. Ocular tolerance studies explicated its safe use. Scintigraphy studies indicated longer retention of CS-PLGA NP's while increased effectiveness after single instillation in reducing the intraocular pressure was observed. CONCLUSION: CS-PLGA-NP's could be successfully formulated and are an excellent vehicle for FK in ocular delivery.


Assuntos
Quitosana , Colforsina/efeitos adversos , Córnea/metabolismo , Dexametasona , Portadores de Fármacos , Ácido Láctico , Nanopartículas , Hipotensão Ocular , Ácido Poliglicólico , Animais , Linhagem Celular , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Colforsina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Dexametasona/química , Dexametasona/farmacocinética , Dexametasona/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Cabras , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Hipotensão Ocular/induzido quimicamente , Hipotensão Ocular/tratamento farmacológico , Hipotensão Ocular/metabolismo , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos
15.
PLoS One ; 13(3): e0194620, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29554138

RESUMO

Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL). Following delivery by the pulmonary or subcutaneous routes, the immunogenicity and protective efficacy of these vaccines were assessed in a murine model of M. tuberculosis infection. When delivered peripherally, these vaccines induced modest, antigen-specific Th1 and Th17 responses, but strong anti-MPT83 antibody responses. Mucosal delivery of the PLGA(MPT83) vaccine, with or without TDB, increased antigen-specific Th17 responses in the lungs, however, PLGA-encapsulated vaccines did not provide protection against M. tuberculosis challenge. By contrast, peripheral delivery of DDA liposomes containing MPT83 and TDB or MPL, stimulated both Th1 and Th17 responses and generated protection against M. tuberculosis challenge. Therefore, PLGA-formulated vaccines primarily stimulate strong humoral immunity, or Th17 responses if used mucosally, and may be a suitable carrier for vaccines against extracellular pathogens. This study emphasises the critical nature of the vaccine carrier, adjuvant and route of delivery for optimising vaccine efficacy against TB.


Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade Humoral/efeitos dos fármacos , Ácido Láctico/farmacologia , Mycobacterium tuberculosis/imunologia , Ácido Poliglicólico/farmacologia , Células Th17/efeitos dos fármacos , Vacinas contra a Tuberculose/imunologia , Tuberculose/imunologia , Animais , Feminino , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células Th17/imunologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/química , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/farmacologia
16.
Biomed Res Int ; 2018: 3808675, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487867

RESUMO

Postoperative air leaks remain a major cause of morbidity after lung resection. This study evaluated the effect of a combination of polyglycolic acid (PGA) sheet and alginate gel on pulmonary air leaks in rats. Four pulmonary sealing materials were evaluated in lung injury: fibrin glue, combination of PGA sheet and fibrin glue, alginate gel, and combination of PGA sheet and alginate gel. With the airway pressure maintained at 20 cmH2O, a 2 mm deep puncture wound was created on the lung surface using a needle. Lowering the airway pressure to 5 cmH2O, each sealing material was applied. The lowest airway pressure that broke the seal was measured. The seal-breaking pressure in each experimental group was fibrin, 10.4 ± 6.8 cmH2O; PGA + fibrin, 13.5 ± 6.5 cmH2O; alginate gel, 10.3 ± 4.9 cmH2O; and PGA + alginate, 35.8 ± 11.9 cmH2O, respectively. The seal-breaking pressure was significantly greater in the PGA + alginate gel group than in the other groups (p < 0.01). There were no significant differences among the other three groups. Alginate gel combined with a PGA sheet is a promising alternative to fibrin glue as a safe and low-cost material for air leak prevention in pulmonary surgery.


Assuntos
Alginatos/farmacologia , Géis/farmacologia , Lesão Pulmonar/prevenção & controle , Pulmão/efeitos dos fármacos , Ácido Poliglicólico/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Feminino , Adesivo Tecidual de Fibrina/farmacologia , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/farmacologia , Ratos , Ratos Wistar
17.
Biologicals ; 53: 51-62, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29503205

RESUMO

The aim of this study was to synthesize and characterize novel three-dimensional porous scaffolds made of poly (lactic-co-glycolic acid)/TiO2 nanotube (TNT) composite microspheres for bone tissue engineering applications. The incorporation of TNT greatly increases mechanical properties of PLGA/TNT microsphere-sintered scaffold. The experimental results exhibit that the PLGA/0.5 wt% TNT scaffold sintered at 100 °C for 3 h showed the best mechanical properties and a proper pore structure for tissue engineering. Biodegradation test ascertained that the weight of both PLGA and PLGA/PLGA/0.5 wt% TiO2 nanotube composites slightly reduced during the first 4 weeks following immersion in SBF solution. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and alkaline phosphatase activity (ALP activity) results represent increased cell viability for PLGA/0.5%TNT composite scaffold in comparison to the control group. In vivo studies show the amount of bone formation for PLGA/TNT was approximately twice of pure PLGA. Vivid histologic images of the newly generated bone on the implants further supported our test results. Eventually, a mathematical model showed that both PLGA and PLGA/TNT scaffolds' mechanical properties follow an exponential trend with time as their degradation occurs. By a three-dimensional finite element model, a more monotonous distribution of stress was present in the scaffold due to the presence of TNT with a reduction in maximum stress on bone.


Assuntos
Substitutos Ósseos , Osso e Ossos/metabolismo , Ácido Láctico , Teste de Materiais , Ácido Poliglicólico , Engenharia Tecidual , Tecidos Suporte/química , Titânio , Animais , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Osso e Ossos/patologia , Ácido Láctico/química , Ácido Láctico/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Titânio/química , Titânio/farmacologia
18.
Drug Deliv ; 25(1): 166-177, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29299936

RESUMO

Sustained release of therapeutic agents into tumor cells is a potential approach to improve therapeutic efficacy, decrease side effects, and the drug administration frequency. Herein, we used the modified double-emulsion solvent evaporation (DSE) method to prepare a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS). The prepared rough PTX-PLGA-MS possessed microporous surface and highly porous internal structures, which significantly influenced the drug entrapment and release behaviors. The rough MS with an average particle size of 53.47 ± 2.87 µm achieved high drug loading (15.63%) and encapsulation efficiency (92.82%), and provided a favorable sustained drug release. The in vitro antitumor tests of flow cytometry and fluoroimmunoassay revealed that the rough PTX-PLGA-MS displayed effective anti-gliomas activity and enhanced the cellular PTX uptake through adsorptive endocytosis. Both in vitro and in vivo antitumor results demonstrated that the sustained-release PTX could induce the microtubules assembly and the over-expression of Bax and Cyclin B1 proteins, resulting in the microtubule dynamics disruption, G2/M phase arrest, and cell apoptosis accordingly. Furthermore, as the rough PTX-PLGA-MS could disperse and adhere throughout the tumor sites and cause extensive tumor cell apoptosis with one therapeutic course (12 days), they could reduce the system toxicity and drug administration frequency, thus achieving significant tumor inhibitory effects with rapid sustained drug release. In conclusion, our results verified that the rough PTX-PLGA-MS drug release system could serve as a promising treatment to malignant glioma.


Assuntos
Antineoplásicos Fitogênicos/química , Ácido Láctico/química , Paclitaxel/química , Paclitaxel/farmacologia , Ácido Poliglicólico/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Emulsões/química , Emulsões/farmacologia , Feminino , Glioma/tratamento farmacológico , Células Hep G2 , Humanos , Ácido Láctico/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microesferas , Nanopartículas/química , Tamanho da Partícula , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
19.
J Mater Sci Mater Med ; 29(2): 18, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29340853

RESUMO

Biodegradable and bioresorbable polyesters (BBPEs) are a widespread class of aliphatic polymers with a plethora of applications in the medical field. Some reports speculate that these polymers have intrinsic antibacterial activity as a consequence of their acidic degradation by-products. The release of organic acids as a result of the hydrolytic degradation of BBPEs in vivo and the resulting pH drop could be an effective inhibitor of the growth of pathogens in the local environment adjacent to BBPE-based devices. However, there is no clear and conclusive evidence in the literature concerning the antibacterial activity of BBPE to support or refute this hypothesis. In this communication we address this point through an assessment of the antibacterial properties of six well-established commercially available BBPEs. Agar diffusion assays and optical density measurements at 600 nm were performed on all the polymer samples to characterize the growth of bacteria and any potential inhibition over an incubation period of 24 h. The results indicated that BBPEs do not possess an intrinsic and immediate antibacterial activity, which is consistent with the clear mismatch between the time-scales for bacterial growth and the rate of degradation of the polyesters.


Assuntos
Implantes Absorvíveis , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Poliésteres/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/química , Escherichia coli , Hidroxibutiratos/química , Hidroxibutiratos/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacologia , Testes de Sensibilidade Microbiana , Poliésteres/química , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Staphylococcus aureus
20.
Sci Rep ; 8(1): 1447, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29362501

RESUMO

The timing of gene transfection greatly influences stem cell differentiation. Sequential transfection is crucial for regulation of cell behavior. When transfected several days after differentiation initiation, genes expressed at the late stage of differentiation can regulate cell behaviors and functions. To determine the optimal timing of key gene delivery, we sequentially transfected human mesenchymal stem cells (hMSCs). This method can easily control osteogenesis of stem cells. hMSCs were first transfected with RUNX2 and SP7 using poly(lactic-co-glycolic acid) nanoparticles to induce osteogenesis, and then with ATF4 after 5, 7, and 14 days. Prior to transfecting hMSCs with all three genes, each gene was individually transfected and its expression was monitored. Transfection of these genes was confirmed by RT-PCR, Western blotting, and confocal microscopy. The pDNAs entered the nuclei of hMSCs, and RUNX2 and SP7 proteins were translated and triggered osteogenesis. Second, the ATF4 gene was delivered when cells were at the pre-osteoblasts stage. To induce the osteogenesis of hMSCs, the optimal timing of ATF4 gene delivery was 14 days after RUNX2/SP7 transfection. Experiments in 2- and 3-dimensional culture systems confirmed that transfection of ATF4 at 14 days after RUNX2/SP7 promoted osteogenic differentiation of hMSCs.


Assuntos
Fator 4 Ativador da Transcrição/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Dexametasona/farmacologia , Osteogênese/efeitos dos fármacos , Fator de Transcrição Sp7/genética , Fator 4 Ativador da Transcrição/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Ácido Láctico/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Nanosferas , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fator de Transcrição Sp7/metabolismo , Fatores de Tempo , Transfecção
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