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1.
Macromol Biosci ; 24(5): e2300469, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38197551

RESUMO

In order to achieve long-term and controllable release of anti-tumor drugs at specific sites, temperature/pH responsive nanoparticles encapsulating 5-fluorouracil and methotrexate in situ are prepared through dispersion photopolymerization under green LED irradiation. The physicochemical properties of nanoparticles are characterized by scanning electron microscopy, Fourier transform infrared, dynamic light scattering, thermogravimetric/differential scanning calorimetry, and X-ray diffraction. In vitro drug release at different temperatures and pH values is examined to ascertain the release pattern of two drugs, which can be well described by Korsmeyer-Peppas kinetic model. The cytotoxicity evaluation illustrates that the tumor cells could be more effectively killed by the drug-loaded nanoparticles, and the improved therapeutic effect is attributed to the controllable and sustainable drug release as well as the enhanced cellular uptake. The blood safety and good biocompatibility of nanoparticles are further confirmed by hemolysis assay, indicating the prepared nanoparticles are potential candidates for effective tumor treatment.


Assuntos
Fluoruracila , Metotrexato , Nanopartículas , Polimetil Metacrilato , Temperatura , Fluoruracila/farmacologia , Fluoruracila/química , Metotrexato/farmacologia , Metotrexato/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Humanos , Polimetil Metacrilato/química , Polimerização , Hemólise/efeitos dos fármacos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Animais , Difração de Raios X , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/química , Linhagem Celular Tumoral
2.
ACS Appl Mater Interfaces ; 16(31): 40653-40666, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39052487

RESUMO

The key to saving lives is to achieve instant and effective sealing hemostasis in the event of emergency bleeding. Herein, a plant oil-based EMTA/Zn2+ bioadhesive is prepared by a facile reaction of epoxidized soybean oil (ESO) with methacrylic acid (MAA) and tannic acid (TA), followed by the addition of zinc ions for coordination with TA. The EMTA/Zn2+ bioadhesive can be rapidly cured in situ at the wound site through photo-cross-linking under ultraviolet (UV) light-emitting diode (LED) irradiation within 30 s, achieving ultrastrong wet-tissue adhesion performance of 92.4 and 51.8 kPa to porcine skin and aortic skin after 7 days underwater, respectively. Especially, the EMTA/Zn2+ bioadhesive exhibits outstanding sealing performance in vitro with the high burst pressure of 525 mmHg (70 kPa) and 337.5 mmHg (45 kPa) to porcine skin and aortic skin, respectively. Moreover, the EMTA/Zn2+ bioadhesive not only has outstanding hemocompatibility and good biodegradability but also exhibits excellent cytocompatibility and antibacterial properties. Notably, the EMTA/Zn2+ bioadhesive has remarkable instant sealing hemostatic ability for hemorrhaging liver in vivo. Therefore, the prepared plant oil-based EMTA/Zn2+ bioadhesive can serve as a charming alternative candidate for instant sealing hemostasis in clinical applications, especially in traumatic internal organs and arterial bleeding.


Assuntos
Hemostasia , Animais , Suínos , Hemostasia/efeitos dos fármacos , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Zinco/química , Zinco/farmacologia , Camundongos , Humanos , Hemorragia/tratamento farmacológico , Pele/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Taninos/química , Taninos/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia
3.
J Mater Chem B ; 11(8): 1798-1807, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36727624

RESUMO

Combined chemotherapy plays an increasingly important and practical role in the clinical treatment of malignant tumor. In this study, paclitaxel (PTX) and curcumin (Cur) are simultaneously encapsulated into nanogels (termed as NG-PC) in situ by microemulsion photopolymerization at 532 nm for synergistically suppressing breast tumors. NG-PC with a size of 180 nm and a low polydispersity index (PDI < 0.2) presents a controlled and cumulative release of PTX and Cur within 90 h. Moreover, NG-PC displays a remarkable killing effect against 4T1 and MCF-7 cells. In vivo antitumor evaluation on 4T1 tumor-bearing mice demonstrates that NG-PC has significantly higher ability to inhibit tumor growth, inducing necrosis, apoptosis and suppression of proliferation than that of a single drug. Our research provides a facile method to prepare a nano-drug delivery platform with excellent drug co-loading ability and synergistic antitumor effect.


Assuntos
Neoplasias da Mama , Curcumina , Humanos , Camundongos , Animais , Feminino , Paclitaxel/farmacologia , Curcumina/farmacologia , Nanogéis , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico
4.
Colloids Surf B Biointerfaces ; 217: 112611, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35679736

RESUMO

Tumor microenvironment-responsive nanogels loading antitumor drugs can improve the chemotherapy efficiency due to their suitable size, great hydrophilicity, excellent biocompatibility, and sensitivity to specific stimulation. Herein, a simple and effective strategy of one-pot laser-induced emulsion polymerization at 532 nm was developed to prepare carmofur-loaded nanogels based on biocompatible and temperature/pH-sensitive monomers including polyethylene glycol diacrylate (PEGDA), N-vinylcaprolactam (NVCL), and 2-(dimethylamino) ethyl methacrylate (DMAEMA). The nanogels loading carmofur with dual-stimuli responsive drug release properties were rapidly obtained under laser irradiation (beam diameter 2.5 mm, laser power 60 mW) for only 100 s. These nanogels exhibited an average hydrodynamic diameter of 195.9 nm and a low polydispersity index of 0.115. The effect of monomer ratio on the size, morphology, double-bond conversion, and thermo/pH-sensitivity of nanogels was investigated. The cumulative carmofur release from nanogels at pH 5.0 within 48 h was nearly three times that at pH 7.4, while the release amount at 42 °C was twice that at 25 °C, showing the controlled and sustainable release with the change of pH and temperature. The in vitro release kinetics of carmofur was in accord with first-order release model.


Assuntos
Fluoruracila , Lasers , Portadores de Fármacos/química , Emulsões , Fluoruracila/análogos & derivados , Concentração de Íons de Hidrogênio , Nanogéis , Polimerização , Temperatura
5.
Photochem Photobiol ; 98(1): 132-140, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34390000

RESUMO

Nanogel is an important kind of biomaterials applied for wound dressings, drug delivery, medical diagnostics and biosensors. The properties of nanogels closely depend on the density of the crosslinking network. In this study, the role of triethanolamine (TEOA) in the effect on the crosslinking degree of nanogels based on poly(ethylene glycol) diacrylate (PEGDA) was investigated and illustrated. The effect of TEOA on the process of photopolymerization at 532 nm and properties of the nanogels was systematically investigated by using UV-vis spectroscopy, FT-IR spectroscopy, 1 H NMR, DLS, SEM, AFM and DSC. In brief, the double-bond conversion of photopolymerization and the crosslinking degree of nanogels can be effectively regulated by TEOA.


Assuntos
Etanolaminas , Polietilenoglicóis , Sistemas de Liberação de Medicamentos , Nanogéis , Polietilenoglicóis/química , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Int J Biol Macromol ; 214: 120-127, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35661672

RESUMO

Collagen (Col) films were reinforced by celluloses in different geometries: microcrystalline cellulose (MCC), cellulosic fines (CF), cellulose nanofiber (CNF) and cellulose nanocrystals (CNC). The reinforcement mechanisms were investigated by the elastoplasticity and fracture appearance. Compared with the fracture stress of collagen film (67.5 MPa), the Col-CNF films effectively borne the stress (95.8 MPa) by intercrystalline fracture, ascribing the abundant hydrogen bonding and mechanical locking between cellulose and collagen. The toughness of Col-CF films was increased by the interfibrillar slippage of CF and pull-off of CF within the matrix, improving the strain-to-break from 8.37% to 12.13%. The films added with MCC and CNC weaken the mechanical behavior, due to the defects and lack of mechanical locking. Besides, the effects of celluloses' geometries on the thickness, density, water-tightness, thermal stability, crystallinity and FTIR of films were also investigated. These provide the evidence that the geometries of fillers diversely improve the behaviors of collagen film offering strategies for the film with adjustable mechanical properties.


Assuntos
Nanofibras , Nanopartículas , Celulose/química , Colágeno/química , Nanopartículas/química , Água/química
7.
J Mater Chem B ; 10(17): 3293-3302, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35380157

RESUMO

Drug-loaded nanogels for cancer treatment can limit the free diffusion and distribution of drug molecules in the whole body to reduce undesirable side effects and improve the drug absorption efficiency of the tumor. In this study, curcumin as a model drug was encapsulated into nanogels in situ through microemulsion photopolymerization at 532 nm. Nanogels loaded with curcumin (NG-C) displayed a diameter of around 150 nm with good stability and a low polydispersity index of around 0.1. NG-C had a drug-loading capacity of 8.96 ± 1.16 wt%. The cumulative release of curcumin from NG-C was around 25%, 34% and 55% within 90 h in pH 7.4, 6.8 and 5.0 PBS buffer, respectively. NG-C presented prominent cytotoxicity toward Hep G2 and HeLa cancer cells in vitro. Moreover, NG-C exhibited much a stronger inhibition of tumor growth, necrosis, apoptosis, and the suppression of proliferation compared with curcumin on Hep G2 tumor-bearing nude mice.


Assuntos
Curcumina , Animais , Apoptose , Curcumina/química , Células HeLa , Humanos , Camundongos , Camundongos Nus , Nanogéis
8.
Colloids Surf B Biointerfaces ; 206: 111943, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34243031

RESUMO

The strategy of laser beam expansion was used to rapidly prepare nanogels by photopolymerization at 532 nm under low monomer concentration. According to the unique micellar morphology formed by amphiphilic polyethylene glycol diacrylate (PEGDA) in water, the monomer concentration was largely decreased to increase the distance of micellar aggregates. In this case, the photo-crosslinking could prefer to occur inside the micelles instead of crosslinking between the micellar aggregates. The variations of double bond content with reaction time in different beam expansion experiments were investigated. Finally, nanogels with uniform size could be rapidly prepared by regulating the reaction parameters, including monomer concentration, reaction time and power density.


Assuntos
Micelas , Polietilenoglicóis , Nanogéis , Água
9.
Biomacromolecules ; 11(9): 2306-12, 2010 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-20666510

RESUMO

We studied methoxy poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-dimethylaminoethyl methacrylate) (mPEG-b-PCL-b-PDMAEMA) nanoparticles as the codelivery vector of hydrophobic drug and pDNA by employing dynamic light scattering (DLS), ζ potential, transmission electron microscopy (TEM), gel retardation assay, and confocal microscopy, and subsequently its in vitro cytotoxicity and transfection efficiency were tested. mPEG-b-PCL-b-PDMAEMA nanoparticles (NPs) with or without paclitaxel are both able to complex with pDNA completely when N/P ratio is equal to or above 3, and the combinatorial deliveries of paclitaxel and pDNA have equivalent transfection efficiency compared to blank NPs/pDNA complexes when N/P ratio is equal to or above 15, which indicates that the payload of hydrophobic drug does not influence pDNA condensation and transfection efficiency. Importantly, the in vitro cell experiment results confirm that the introduction of hydrophobic segment between mPEG and PDMAEMA segments can largely improve the gene transfection efficiency, which is about 15 times that of mPEG-b-PDMAEMA. NPs/pDNA complexes can be efficiently internalized into 293T cells after transfection for 2 h. The drug release rate of paclitaxel-loaded NPs in pH 5.0 release medium is higher than that in pH 7.2 release medium. These results suggest that mPEG-b-PCL-b-PDMAEMA NPs may be a promising vector to deliver anticancer drugs and pDNA simultaneously for achieving the synergistic/combined effect on cancer therapies.


Assuntos
DNA/administração & dosagem , Sistemas de Liberação de Medicamentos , Rim/efeitos dos fármacos , Nanopartículas , Paclitaxel/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/síntese química , Polímeros/administração & dosagem , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/síntese química , Antineoplásicos Fitogênicos/farmacologia , Cátions , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA/genética , DNA/metabolismo , Portadores de Fármacos , Sinergismo Farmacológico , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Rim/citologia , Polietilenoglicóis/administração & dosagem , Polímeros/síntese química , Polímeros/química , Compostos de Amônio Quaternário/administração & dosagem
10.
J Mater Chem B ; 8(12): 2431-2437, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32104870

RESUMO

Fluorescent probes have been widely used in bioimaging as an efficient and convenient analytical tool. From the initial inorganic nanoparticles and small organic molecules to polymeric nanoparticles, scientific researchers have been trying to develop a probe with strong fluorescence and excellent biocompatibility. In this study, a tetraphenylethylene derivative with AIE properties and hyaluronic acid modified by methacrylic anhydride were combined to prepare a novel nanoparticle (HA-Ac-Pha-C) as a fluorescent probe by a photochemical cross-linking reaction. The fluorescence intensity and size of the nanoparticles were characterized by different techniques. It was confirmed that cross-linked nanoparticles not only showed stronger fluorescence, but also had better photostability while still maintaining 85.9% of the initial intensity after seven days. Moreover, cells and zebrafish imaging experiments also demonstrated that nanoparticles show specific fluorescence labeling for cancer cells and excellent biocompatibility in living organisms.


Assuntos
Materiais Biocompatíveis/química , Reagentes de Ligações Cruzadas/química , Corantes Fluorescentes/química , Nanopartículas/química , Imagem Óptica , Animais , Materiais Biocompatíveis/síntese química , Linhagem Celular , Reagentes de Ligações Cruzadas/síntese química , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Ácido Hialurônico/química , Estrutura Molecular , Tamanho da Partícula , Estilbenos/química , Propriedades de Superfície , Peixe-Zebra
11.
Pharm Res ; 26(6): 1398-406, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19225873

RESUMO

PURPOSE: In transdermal drug delivery system (TDDS), chemical enhancers and crystallization inhibitors added into the adhesive matrixes to improve drug permeation and formulation stability often result in some negative effect on adhesive properties and dressing performance. The aim of this paper is to develop a hydrophilic pressure sensitive adhesive (PSA) for TDDS without using additional chemical enhancers and crystallization inhibitors. METHODS: A quaternary blend (PDGW) composed of polyvinyl pyrrolidone, D,L-lactic acid oligomers, glycerol and water was prepared. The adhesive strength, drug loading capacity, drug state and stability of PDGW were characterized by using ibuprofen (IBU) and salicylic acid (SA) as model drugs. Moreover, In vitro and in vivo drug permeation through rat skin from PDGW patch in comparison to acrylate adhesive (ACA) and nature rubber adhesive (NRA) was investigated. RESULTS: PDGW performs excellent drug loading and crystallization inhibition capacity. Furthermore, the accumulative amount for 24 h in vitro from PDGW patch is far higher than that from ACA and NRA patch. And the plasma concentration of drugs in vivo from PDGW patch is bigger than that from ACA patch. CONCLUSIONS: PDGW possesses excellent PSA properties and self-enhancement for drug percutaneous permeation, which can be used to develop new formulation of TDDS.


Assuntos
Adesivos/química , Analgésicos não Narcóticos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Ibuprofeno/administração & dosagem , Ácido Salicílico/administração & dosagem , Pele/metabolismo , Administração Cutânea , Analgésicos não Narcóticos/sangue , Analgésicos não Narcóticos/química , Animais , Anti-Infecciosos/sangue , Anti-Infecciosos/química , Estabilidade de Medicamentos , Glicerol/química , Ibuprofeno/sangue , Ibuprofeno/química , Ácido Láctico/química , Povidona/química , Pressão , Ratos , Ácido Salicílico/sangue , Ácido Salicílico/química , Água/química
12.
Sci Rep ; 9(1): 8183, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160669

RESUMO

The maize stalk is an important mechanical supporting tissue. The stalk fracture resistance is closely related to lodging resistance, and thus the yield. In this study, we showed that the basal zone (BZ) was more fragile than the middle zone (MZ) of the stalk internode before tasseling. In order to clarify the relationship between the different zones and fragile resistance between the internodes, we systematically analyzed the phenotypic, metabolomic and transcriptomic differences. The results indicated that the BZ zone had lower stalk strength, which corresponded to the results of less lignin, cellulose and hemicellulose than that of the MZ. The 27 highly enriched metabolites and 4430 highly expressed genes in the BZ mainly participated in pentose phosphate, and in ribosome and sterol synthesis pathways, respectively. In addition, the BZ had higher vascular bundles density but smaller size compared with the MZ. By contrast, the 28 highly enriched known metabolites and 4438 highly expressed genes in the MZ were mainly involved in lignin synthesis, and secondary metabolites synthesis, respectively, especially the phenylpropanoid synthesis. The results provide a deeper understanding of the relationship between development and fracture differences in stalk, and may facilitate the improvement of field management practice to reduce lodging.


Assuntos
Celulose/genética , Proteínas de Plantas/genética , Zea mays/genética , Parede Celular/genética , Celulose/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Lignina/genética , Fenótipo , Locos de Características Quantitativas/genética , Zea mays/metabolismo
13.
Int J Biol Macromol ; 120(Pt B): 2086-2093, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30195610

RESUMO

The modified collagen with double bonds was electrospun into nanofibers membrane cured with photo-initiated polymerization under UV irradiation. The morphology and chemical structures were characterized by SEM and FTIR. Both the water resistance and mechanical properties were improved after UV-crosslinking. Then 5-Fluorouracil (5-FU) was used as a model drug to prepare drug-loaded collagen nanofiber membrane cured with photo-initiated polymerization under UV irradiation. In vitro release results showed that drug release could be effectively controlled through UV-crosslinking. Furthermore, the release mechanism of drugs from electrospun mats was confirmed to be Fickian diffusion.


Assuntos
Colágeno/química , Portadores de Fármacos/química , Eletricidade , Nanofibras/química , Raios Ultravioleta , Liberação Controlada de Fármacos , Fluoruracila/química , Fenômenos Mecânicos , Membranas Artificiais , Modelos Moleculares , Conformação Proteica , Água/química
14.
Int J Biol Macromol ; 85: 252-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26763174

RESUMO

Protein adsorption is considered as an important factor for the low transfection efficiency of polycations in vivo. In this study, two typical polycations of equal molecular weight with different structures were chosen to investigate their adsorption on bovine serum albumin (BSA), including the block copolymer named poly (N-vinylpyrrolidone)-b-poly (2-dimethylaminoethyl methacrylate) (PVP-b-PDMAEMA, i.e. PbP) and graft copolymer named PVP-g-PDMAEMA (PgP), respectively. Fluorescence spectroscopy was used to confirm the binding constants and binding sites between polycations and BSA in static state. The binding constants were 4.1×10(4)M(-1) vs 8.3×10(4)M(-1) and binding sites were 0.3 vs 1.1 for PbP and PgP, respectively, indicating PgP had stronger binding affinity with BSA. Surface plasmon resonance (SPR) was used to study the dynamical non-specific interaction between BSA and polycations as well as the polyplexes. The numbers of both PbP and PgP adsorbed on BSA increased with concentration of polycations increasing, and the number of PgP adsorbed on BSA is higher compared with PbP when their concentration is low. When their concentration is high, the number of PbP adsorbed on BSA is more than that of PgP. However, PgP/DNA polyplexes showed higher adsorption amount compared with PbP/DNA polyplexes at different N/P ratios.


Assuntos
Estrutura Molecular , Poliaminas/química , Soroalbumina Bovina/química , Adsorção , DNA/química , Cinética , Modelos Moleculares , Polieletrólitos , Polímeros/química , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície
15.
J Biomater Sci Polym Ed ; 24(1): 45-60, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22289623

RESUMO

Novel well-defined hydrophilic cationic polymers with different length of polycation chain for gene delivery, poly(vinyl pyrrolidone)-graft-poly(2-dimethylaminoethyl methacrylate)s (PPDs), were synthesized by atom transfer radical polymerization (ATRP). The chemical structures and compositions of these polymers were characterized by FT-IR, (1)H-NMR and GPC. The experimental results of dynamic light scattering (DLS), ζ-potential and transmission electron microscopy (TEM) indicated that PPD could condense plasmid DNA (pDNA) to form nanocomplexes. Agarose gel retardation assays demonstrated that PPD could encapsulate plasmid DNA completely when the N/P ratio is equal to or above 3. MTT assay and in vitro gene transfection results indicated that PPD/pDNA complexes exhibited high transfection efficiency concomitant with obvious cytotoxicity. Furthermore, bovine serum albumin (BSA) was utilized to assembly with the binary complexes of PPD/pDNA to screen the residual surface positive charges of complexes in order to decrease cytotoxicity of the binary complexes. Physicochemical properties were characterized and the results indicated that the coating of BSA was able to decrease the zeta potential of the nano-sized PPD/pDNA complexes nearly to electroneutrality without interfering with DNA condensation ability. The ternary complexes of BSA/PPD/pDNA demonstrated no cytotoxicity and also maintained high gene transfection efficiency in HepG2 cells in 10% serum compared with that in serum-free condition.


Assuntos
Materiais Revestidos Biocompatíveis/química , DNA/administração & dosagem , Etilaminas/química , Metacrilatos/química , Povidona/química , Soroalbumina Bovina/química , Transfecção , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/toxicidade , DNA/genética , Etilaminas/toxicidade , Células Hep G2 , Humanos , Metacrilatos/toxicidade , Plasmídeos/administração & dosagem , Plasmídeos/genética , Povidona/toxicidade , Soroalbumina Bovina/toxicidade
16.
Colloids Surf B Biointerfaces ; 96: 56-61, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22516713

RESUMO

A novel temperature-response hydrogel was developed for drug-delivery applications. The hydrogel matrix (PES) was synthesized by melt polycondensation of poly(ether-ester) diacid based on PEG with low molecular weight and sebacic acid. The sol-gel-sol phase transitions of PES nanoparticle (NP) hydrogel were investigated. In vitro erosion of hydrogel was characterized by Fourier transform infrared spectroscopy, environmental scanning electron microscopy and dynamic light scattering. In vitro release behaviors of hydrophilic and hydrophobic drugs and in vivo histopathological evaluation were studied in detail. The study results revealed that an aqueous dispersion of PES nanoparticle freeze-dried powder exhibited reversible sol-gel transition behavior with increasing temperature. The hydrogel could maintain steadily at least a month during in vitro erosion process. There were sustained release behaviors of hydrophilic and hydrophobic drugs from PES NP hydrogel and histopathological studies confirmed that the PES NP hydrogel only provoked an acceptable modest inflammatory response. Thus, PES NP hydrogel is biodegradable, biocompatible and promising in controlling the incorporated drugs for sustained release.


Assuntos
Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanopartículas/química , Anidridos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Derme/metabolismo , Derme/patologia , Dexametasona/administração & dosagem , Dexametasona/química , Dexametasona/farmacocinética , Composição de Medicamentos/métodos , Éter/química , Fluoruracila/administração & dosagem , Interações Hidrofóbicas e Hidrofílicas , Injeções Subcutâneas , Luz , Camundongos , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Paclitaxel/administração & dosagem , Paclitaxel/química , Paclitaxel/farmacocinética , Transição de Fase , Poliésteres/química , Espalhamento de Radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
17.
Biomaterials ; 33(18): 4653-64, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22480869

RESUMO

Small interfering RNA (siRNA) is a powerful gene silencing tool and has promising prospects in basic research and the development of therapeutic reagents. However, the lack of an effective and safe tool for siRNA delivery hampers its application. Here, we introduced binary and ternary complexes that effectively mediated siRNA-targeted gene silencing. Both complexes showed excellent siRNA loading even at the low N/P/C ratio of 3:1:0. FACS and confocal microscopy demonstrated that nearly all cells robustly internalized siRNAs into the cytoplasm, where RNA interference (RNAi) occurred. Luciferase assay and Western blot verified that silencing efficacy reached >80%, and introducing folate onto the ternary complexes further enhanced silencing efficacy by about 10% over those without folate at the same N/P/C ratio. In addition, the coating of PGA-g-mPEG decreased the zeta potential almost to electroneutrality, and the MTT assay showed decreased cytotoxicity. In vivo distribution measurement and histochemical analysis executed in C57BL/6 and Hela tumor-bearing BALB/c nude mice showed that complexes accumulated in the liver, lungs, pancreas and tumors and were released slowly for a long time after intravenous injection. Furthermore, ternary complexes showed higher siRNA fluorescence intensity than binary complexes at the same N/P ratio in tumor tissues, those with folate delivered more siRNAs to tumors than those without folate, and more folate induced more siRNA transport to tumors. In addition, in vivo functional study showed that both binary and ternary complexes mediated down-regulation of ApoB in liver efficiently and consequently blocked the secretion of fatty acids into the blood, resulted in lipid accumulation in liver, liver steatosis and hepatic dysfunction. In conclusion, these complexes provided a powerful means of administration for siRNA-mediated treatment of liver-related diseases and various cancers, especial for pancreatic and cervical cancer.


Assuntos
Vetores Genéticos/administração & dosagem , Vetores Genéticos/química , Metilmetacrilatos/química , Poliésteres/química , Polímeros/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , Animais , Western Blotting , Feminino , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Biomaterials ; 32(33): 8730-42, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21885115

RESUMO

The multiformity in polymer structure and conformation design provides a great potential in improving the gene silencing efficiency of siRNA by polymer vectors. In order to provide information on the polymer design for siRNA delivery, the structural contributions of blocked or grafted poly(2-dimethylaminoethyl methacrylate) on PEGylated polycaprolactone nanoparticles (NPs) in siRNA delivery were studied. Herein, two kinds of self-assembly nanoparticles (NPs) formed by amphiphilic cationic polymers, methoxy poly(ethylene glycol)-block-polycaprolactone-block-poly(2-dimethylaminoethyl methacrylate) (mPEG-PCL-b-PDMAEMA, PECbD) and methoxy poly(ethylene glycol)-block-(polycaprolactone-graft-poly(2-dimethylaminoethyl methacrylate)) (mPEG-PCL-g-PDMAEMA, PECgD), were used to deliver siRNA for in vitro and in vivo studies. The physiochemical properties including size and zeta potential of PECbD NPs/siRNA and PECgD NPs/siRNA complexes were characterized. In vitro cytotoxicity, cellular uptake and siRNA knockdown efficiency were evaluated in HeLa-Luc cells. The endosome escape and intracellular distribution of PECbD NPs/siRNA and PECgD NPs/siRNA in HeLa-Luc cells were also observed. In vivo polymer mediated siRNA delivery and the complexes distribution in isolated organs were studied using mice and tumor-bearing mice. At the same total degree of polymerization (DP) of DMAEMA, PECgD NPs/siRNA complexes possessed higher zeta potentials than PECbD NPs/siRNA complexes (at the same N/P ratio), which may be the reason that PECgD NPs/siRNA complexes can deliver more siRNA into the cytoplasm and lead to higher in vitro luciferase and lamin A/C silencing efficiency than PECbD NPs/siRNA complexes. The in vivo imaging measurement and histochemical analysis also confirmed that siRNA could be delivered to lungs, livers, pancreas and HeLa-Luc tumors more efficiently by PECgD NPs than PECbD NPs. Meanwhile, the PDMAEMA chains of PECgD could be shortened which provides benefits for clearing. Therefore, PECgD NPs have great potential to be used as efficient non-viral carriers for in vivo siRNA delivery.


Assuntos
Metacrilatos/química , Nanopartículas , Nylons/química , Poliésteres/química , RNA Interferente Pequeno/administração & dosagem , Animais , Sequência de Bases , Eletroforese em Gel de Ágar , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular
19.
Biomaterials ; 32(18): 4283-92, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21450341

RESUMO

Binary complexes of cationic polymers and DNA were used commonly for DNA delivery, whereas, the excess cationic charge of the binary complexes mainly leads to high toxicity and unstability in vivo. In this paper, ternary complexes by coating polyglutamic acid-graft-poly(ethylene glycol)(PGA-g-mPEG) onto binary complexes of polycaprolactone-graft-poly(N,N-dimethylaminoethyl methacrylate) (PCL-g-PDMAEMA) nanoparticles (NPs)/DNA were firstly developed for effective and targeted gene delivery. The coating of PGA-g-mPEG was able to decrease the zeta potential of the nano-sized DNA complexes nearly to electroneutrality without interferring with DNA condensation ability. As a result, the stability, the escape ability from endosomes and the transfection efficiency of the complexes were enhanced. The ternary complexes of PCL-g-PDMAEMA NPs/DNA/PGA-g-mPEG demonstrated lower cytotoxicity in CCK-8 measurements and higher gene transfection efficiency than the binary complexes in vitro. In addition, Lactate dehydrogenase (LDH) assay was performed to quantify the membrane-damaging effects of the complexes, which is consistent with the conclusion of CCK-8 measurement for cytotoxicity assay. The in vivo imaging measurement and histochemical analysis of tumor sessions confirmed that the intravenous administration of the ternary complexes with red fluorescent protein (RFP) as payload led to protein expression in tumor, which was further enhanced by the targeted coating of PGA-g-PEG-folate.


Assuntos
DNA/química , Técnicas de Transferência de Genes , Metacrilatos/química , Poliésteres/química , Polietilenoglicóis/química , Ácido Poliglutâmico/química , Animais , Terapia Genética/métodos , Células HeLa , Humanos , Camundongos , Camundongos Nus , Modelos Moleculares , Nanopartículas/química , Tamanho da Partícula , Sincalida/metabolismo
20.
Biomaterials ; 32(3): 879-89, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20970186

RESUMO

A group of amphiphilic cationic polymers, methoxy polyethylene glycol-block-(polycaprolactone-graft-poly(2-(dimethylamino)ethyl methacrylate)) (PECD), were synthesized by combining ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) methods to form nanoparticles (NPs). The structures of these amphiphilic cationic polymers were characterized by (1)H NMR measurement. The PECD NPs have hydrophobic cores covered with hydrophilic PEG and cationic PDMAEMA chains. These self-assembly nanoparticles were characterized by dynamic light scattering (DLS) technique. PECD NPs can effectively condense DNA to form compact complexes of the size 65-160 nm suitable for gene delivery. The in vitro gene transfection studies of HeLa and HepG2 cells show that PECD NPs have better transfection efficiency compared to polyethylenimine (PEI) and Lipofectamine 2000 at low dose (N/P = 5). The cytotoxicity result shows that PECD NPs/DNA complexes at the optimal N/P ratio for transfection have comparable toxicity with PEI and Lipofectamine. These results indicate that PECD NPs have a great potential to be used as efficient polymeric carriers for gene transfection.


Assuntos
Materiais Biocompatíveis/química , Metacrilatos/química , Nylons/química , Poliésteres/química , Polietilenoglicóis/química , Polímeros/química , Sobrevivência Celular , Eletroforese em Gel de Ágar , Terapia Genética/métodos , Células HeLa , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Nanopartículas/química , Transfecção/métodos
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