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1.
J Nanobiotechnology ; 19(1): 138, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985511

RESUMO

BACKGROUND: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. RESULTS: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. CONCLUSIONS: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.


Assuntos
Quimiorradioterapia/métodos , Cisplatino/química , Cisplatino/farmacologia , Nanopartículas/química , Polímeros/química , Receptor ErbB-2/química , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Humanos , Compostos de Manganês , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/uso terapêutico , Óxidos , Radiossensibilizantes , Espécies Reativas de Oxigênio/metabolismo , Receptor ErbB-2/genética , Hipóxia Tumoral , Microambiente Tumoral
2.
J Nanobiotechnology ; 17(1): 60, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31084622

RESUMO

BACKGROUND: Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells. RESULTS: In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations. CONCLUSIONS: Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.


Assuntos
Antineoplásicos/química , Materiais Biomiméticos/química , Bufanolídeos/química , Portadores de Fármacos/química , Nanopartículas/química , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Transporte Biológico , Plaquetas/metabolismo , Bufanolídeos/efeitos adversos , Bufanolídeos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Oligossacarídeos/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Distribuição Tecidual
3.
Int J Pharm ; 656: 124093, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38583822

RESUMO

A multifunctional nanoplatform was constructed in this work, with the goal of ameliorating the challenges faced with traditional cancer chemotherapy. Cisplatin (CP) was loaded into mesoporous polydopamine (mPDA) nanoparticles (NPs) with a drug loading of 15.8 ± 0.1 %, and MnO2 used as pore sealing agent. Finally, the NPs were wrapped with platelet membrane (PLTM). P-selectin on the PLTM can bind to CD44, which is highly expressed on the tumor cell membrane, so as to improve the targeting performance of the NPs. In addition, the CD47 on the PLTM can prevent the NPs from being phagocytosed by macrophages, which is conducive to immune escape. The final PLTM-CP@mPDA/MnO2 NPs were found to have a particle size of approximately 198 nm. MnO2 is degraded into Mn2+ in the tumor microenvironment, leading to CP release from the pores in the mPDA. CP both acts as a chemotherapy agent and can also increase the concentration of H2O2 in cells. Mn2+ can catalyze the conversion of H2O2 to OH, resulting in oxidative damage and chemodynamic therapy. In addition, Mn2+ can be used as a contrast agent in magnetic resonance imaging (MRI). In vitro and in vivo experiments were performed to explore the therapeutic effect of the NPs. When the concentration of CP is 30 µg/mL, the NPs cause approximately 50 % cell death. It was found that the PLTM-CP@mPDA/MnO2 NPs are targeted to cancerous cells, and in the tumor site cause extensive apoptosis. Tumor growth is thereby repressed. No negative off-target side effects were noted. MRI could be used to confirm the presence of the NPs in the tumor site. Overall, the nano-platform developed here provides cooperative chemotherapy and chemodynamic therapy, and can potentially be used for effective cancer treatment which could be monitored by MRI.


Assuntos
Antineoplásicos , Plaquetas , Cisplatino , Indóis , Compostos de Manganês , Nanopartículas , Óxidos , Polímeros , Compostos de Manganês/química , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Cisplatino/química , Polímeros/química , Indóis/química , Indóis/administração & dosagem , Animais , Óxidos/química , Nanopartículas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Camundongos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Liberação Controlada de Fármacos , Porosidade , Camundongos Endogâmicos BALB C , Imageamento por Ressonância Magnética , Portadores de Fármacos/química , Feminino , Peróxido de Hidrogênio , Tamanho da Partícula , Camundongos Nus
4.
ACS Appl Bio Mater ; 5(1): 123-133, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35014822

RESUMO

Bringing together photothermal therapy and chemotherapy (photothermal-chemotherapy, PT-CT) is a highly promising clinical approach but requires the development of intelligent multifunctional delivery vectors. In this work, we prepared mesoporous polydopamine nanoparticles (MPDA NPs) loaded with the chemotherapeutic drug doxorubicin (DOX). These NPs were then coated with the platelet membrane (PLTM). The coated MPDA NPs are spherical and clearly mesoporous in structure. They have a particle size of approximately 184 nm and pore size of ca. 45 nm. The NPs are potent photothermal agents and efficient DOX carriers, with increased rates of drug release observed in vitro in conditions representative of the tumor microenvironment. The NPs are preferentially taken up by cancer cells but not by macrophage cells, and while cytocompatible with healthy cells are highly toxic to cancer cells. An in vivo murine model of human breast cancer revealed that the NPs can markedly slow the growth of a tumor (ca. 9-fold smaller after 14 days' treatment), have extended pharmacokinetics compared to free DOX (with DOX still detectable in the bloodstream after 24 h when the NPs are applied), and are highly targeted with minimal off-site effects on the heart, liver, spleen, kidney, and lungs.


Assuntos
Neoplasias da Mama , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Modelos Animais de Doenças , Doxorrubicina/farmacologia , Feminino , Humanos , Indóis , Camundongos , Nanopartículas/uso terapêutico , Polímeros , Microambiente Tumoral
5.
Macromol Rapid Commun ; 32(9-10): 744-50, 2011 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-21438063

RESUMO

Based on a modified coaxial electrospinning process and suitable selection of solvent mixtures as sheath fluid, a new strategy is presented for systematically improving polymer nanofiber quality. A concentric spinneret with an indented inner capillary is designed for the modified coaxial electrospinning. With a solution of 12% w/v PVP K60 in ethanol as the core electrospinning fluid, six solvents are used as sheath fluids to investigate the impact of solvent properties on the resultant PVP nanofiber quality. The PVP nanofiber quality is closely related to solvent physical-chemical properties. High quality PVP nanofibers of average diameter 130 ±10 nm with homogeneous structures and smooth surfaces are created using a solvent mixture of acetone, ethanol and DMAc in the ratio of 3:1:1(v/v/v).


Assuntos
Eletroquímica/métodos , Nanofibras/química , Polímeros/química , Eletroquímica/instrumentação , Polímeros/síntese química , Propriedades de Superfície
6.
Huan Jing Ke Xue ; 42(11): 5193-5200, 2021 Nov 08.
Artigo em Zh | MEDLINE | ID: mdl-34708958

RESUMO

The emission characteristics of VOCs from three typical rubber manufacture industries were studied by GC-MS/FID. Maximum incremental reactivity(MIR) and fractional aerosol coefficient(FAC) were employed to evaluate the ozone formation potential(OFP) and secondary organic aerosol(SOA) formation potential. The results show that the VOC types emitted from the manufacturing of rubber products mainly include alkanes, ketones, aldehydes, alcohols, and benzene series. For traditional rubber products manufactured through rubber mixing and vulcanization, the main pollutants are ketones and alcohols, whereas for production processes involving gluing and painting, the main pollutants belong to the benzene series. In terms of ozone impact, the traditional processes contribute to ozone formation mainly through oxygenated hydrocarbons. In industries that utilize adhesives and paints, the extensive use of these organic solvents lead to a significantly higher contribution of the benzene series than other VOC species to ozone formation; the benzene series account for 82.9% of the total contribution. In terms of SOA impact, the benzene series are the main contributor to SOA, whereas the contribution of VOCs from traditional processes is small; hence, SOA primarily originates from the gluing and painting processes. Therefore, in traditional production of rubber products through rubber mixing and vulcanization, the emission of oxygenated hydrocarbons should be preferentially controlled, whereas for rubber industries utilizing gluing and painting processes, the emission of benzene series should be preferentially controlled.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Borracha , Compostos Orgânicos Voláteis/análise
7.
J Mater Sci Mater Med ; 21(8): 2403-11, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20499138

RESUMO

Cellulose acetate (CA) fibers loaded with the ester prodrugs of naproxen, including methyl ester, ethyl ester and isopropyl ester, were prepared through electrospinning using acetone/N,N-dimethylacetamide(DMAc)/ethanol (4:1:1, v/v/v) as solvent. The chemical and morphological characterizations of the medicated fibers were investigated by means of SEM, DSC, XRD and FTIR, as well as the studies of the drug release properties. The results indicated that the morphology and diameter of the fibers were influenced by the concentration of spinning solution, applied voltage, electrospun solvent and the surfactants. The average diameters of the fibers ranged between 100 and 500 nm for three prodrugs. There was good compatibility between CA and three prodrugs in the blended fibers, respectively. In vitro release indicated that constant drug release from the fiber was observed over 6 days. The prodrugs were successfully encapsulated into the fibers, and this system was stable in terms of effectiveness in release.


Assuntos
Celulose/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Ésteres/administração & dosagem , Pró-Fármacos/administração & dosagem , Adesivo Transdérmico , Administração Cutânea , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Celulose/química , Celulose/metabolismo , Sistemas de Liberação de Medicamentos/instrumentação , Ésteres/química , Ésteres/farmacocinética , Ácido Láctico/síntese química , Ácido Láctico/química , Ácido Láctico/metabolismo , Microscopia Eletrônica de Varredura , Microtecnologia/métodos , Modelos Biológicos , Naproxeno/administração & dosagem , Naproxeno/química , Naproxeno/farmacocinética , Ácido Poliglicólico/síntese química , Ácido Poliglicólico/química , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/síntese química , Polímeros/química , Polímeros/metabolismo , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Adv Healthc Mater ; 9(2): e1901307, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31814332

RESUMO

A nanoplatform that integrates diagnostic and therapeutic functions with intrinsic tumor microenvironment-responsive biodegradability is highly desired. Herein, a biodegradable nanotheranostic agent based on hollow mesoporous organosilica nanoparticles (HMONs), followed by encapsulating of heat shock protein 90 (Hsp 90) inhibitor is described. Then, the pore-engineering including gating with bovine serum albumin-iridium oxide nanoparticles (BSA-IrO2 ) and conjugation of polyethylene glycol (PEG) is conducted to yield 17AAG@HMONs-BSA-IrO2 -PEG (AHBIP) nanotheranostics for multimode computed tomography (CT)/photoacoustic (PA) imaging-guided photodynamic therapy (PDT) and low-temperature photothermal therapy (PTT). Such nanoplatforms show extraordinary photothermal conversion efficiency, high cargo loading (35.4% for 17AAG), and stimuli-responsive release of 17AAG for inhibition of Hsp90, which induces cell apoptosis at low-temperatures (≈41 °C). Also, the IrO2 simultaneously endows the nanotheranostics with catalytic activity in triggering the decomposition of H2 O2 into O2 and thus reducing the tumor hypoxia, as well as protecting normal tissues against H2 O2 -induced inflammation. AHBIP shows good photocatalysis activity for PDT as a result of the generation of superoxide anion by laser irradiation. The resulting AHBIP-mediated synergistic PTT/PDT offers an outstanding therapeutic outcome both in vitro and in vivo. Overall, the incorporation of the BSA-IrO2 and biodegradable HMONs into one nanoplatform has great potential for clinical applications.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Benzoquinonas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Lactamas Macrocíclicas/administração & dosagem , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Animais , Anti-Inflamatórios não Esteroides/química , Benzoquinonas/farmacocinética , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular , Feminino , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Humanos , Peróxido de Hidrogênio/química , Irídio/química , Lactamas Macrocíclicas/farmacocinética , Camundongos Endogâmicos C57BL , Camundongos Nus , Oxigênio/farmacocinética , Técnicas Fotoacústicas , Fotoquimioterapia/métodos , Polietilenoglicóis/química , Soroalbumina Bovina/química , Superóxidos/metabolismo , Nanomedicina Teranóstica/instrumentação , Tomografia Computadorizada por Raios X , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Nanotechnology ; 20(5): 055104, 2009 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-19417335

RESUMO

Oral fast-dissolving drug delivery membranes (FDMs) for poorly water-soluble drugs were prepared via electrospinning technology with ibuprofen as the model drug and polyvinylpyrrolidone (PVP) K30 as the filament-forming polymer and drug carrier. Results from differential scanning calorimetry, x-ray diffraction, and morphological observations demonstrated that ibuprofen was distributed in the ultrafine fibers in the form of nanosolid dispersions and the physical status of drug was an amorphous or molecular form, different from that of the pure drug and a physical mixture of PVP and ibuprofen. Fourier-transform infrared spectroscopy results illustrated that the main interactions between PVP and ibuprofen were mediated through hydrogen bonding. Pharmacotechnical tests showed that FDMs with different drug contents had almost the same wetting and disintegrating times, about 15 and 8 s, respectively, but significantly different drug dissolution rates due to the different physical status of the drug and the different drug-release-controlled mechanisms. 84.9% and 58.7% of ibuprofen was released in the first 20 s for FDMs with a drug-to-PVP ratio of 1:4 and 1:2, respectively. Electrospun ultrafine fibers have the potential to be used as solid dispersions to improve the dissolution profiles of poorly water-soluble drugs or as oral fast disintegrating drug delivery systems.


Assuntos
Preparações de Ação Retardada/química , Eletroquímica/métodos , Ibuprofeno/química , Membranas Artificiais , Nanoestruturas/química , Saliva/química , Água/química , Absorção , Administração Oral , Preparações de Ação Retardada/administração & dosagem , Difusão , Ibuprofeno/administração & dosagem , Ibuprofeno/uso terapêutico , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Rotação , Solubilidade
10.
Yao Xue Xue Bao ; 44(10): 1179-82, 2009 Oct.
Artigo em Zh | MEDLINE | ID: mdl-20055145

RESUMO

The improving effect of electrospun drug-loaded nanofibers on the solubility of poorly water-soluble drug was investigated in the present research. Drug-loaded nanofibers were successfully prepared using electrospinning process with helicid as the poorly water-soluble model drug and polyvinylpyrrolidone K60 (PVP K60) as the filament-forming matrix. Scanning electron microscopy observation demonstrated that the nanofibers had a three-dimensional continuous web structure, and had well smooth surface and a diameter between 400-600 nm. X-ray diffraction results suggested that helicid lost its original crystal structure but highly distributed into the nanofibers in an amorphous state, resulting from the hydrogen bonding interactions between the carboxylic group of PVP K60 and the hydroxyl groups of helicid. The drug-loaded nanofibers obviously improved helicid's solubility, and were able to completely release the whole drug in 60 s. Electrospun drug-loaded nanofibers can improve the solubility and release profiles of poorly water-soluble drug.


Assuntos
Benzaldeídos/química , Nanofibras , Povidona/química , Solubilidade , Benzaldeídos/administração & dosagem , Portadores de Fármacos , Composição de Medicamentos , Técnicas Eletroquímicas/métodos , Microscopia Eletrônica de Varredura , Nanofibras/química , Nanofibras/ultraestrutura , Preparações Farmacêuticas/química , Espectrofotometria Ultravioleta , Difração de Raios X
11.
Colloids Surf B Biointerfaces ; 183: 110411, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421404

RESUMO

In this work, we report new formulations for the combined photo-chemotherapy of colon cancer. Fibers were fabricated via coaxial-electrospinning with the intent of targeting delivery of the anti-cancer drug carmofur (CAR) and the photosensitizer rose bengal (RB) selectively to the colon site. The fibers comprised a hydroxypropyl methylcellulose (HPMC) core loaded with the active ingredients, and a pH-sensitive Eudragit L100-55 shell. The fibers were found to be homogeneous and cylindrical and have visible core-shell structures. X-ray diffraction and differential scanning calorimetry demonstrated that both CAR and RB were present in the fibers in the amorphous physical form. In vitro drug release studies showed that the fibers have the potential to selectively deliver drugs to the colon, with only 10-15 % release noted in the acidic conditions of the stomach but sustained release at pH 7.4. Cytotoxicity studies were undertaken on human dermal fibroblast (HDF) and colon cancer (Caco-2) cells, and the influence of light on cell death was also explored. The fibers loaded with CAR alone showed obvious toxicity to both cell lines, with and without the application of light. The RB-loaded fibers led to high viability (ca. 80% for both cell types) in the absence of light, but much greater toxicity was noted (30-50%) with light. The same trends were observed with the formulation containing both CAR and RB, but with lower viabilities. The RB and RB/CAR loaded systems show clear selectivity for cancerous over non-cancerous cells. Finally, mucoadhesion studies revealed there were strong adhesive forces between the rat colonic mucosa and the fibers after they had passed through an acidic environment. Such electrospun fibers thus could have potential in the development of oral therapies for colon cancer.


Assuntos
Antineoplásicos/farmacologia , Portadores de Fármacos , Fluoruracila/análogos & derivados , Nanofibras/química , Fármacos Fotossensibilizantes/farmacologia , Rosa Bengala/farmacologia , Resinas Acrílicas/química , Administração Oral , Animais , Antineoplásicos/química , Células CACO-2 , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Combinação de Medicamentos , Técnicas Eletroquímicas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fluoruracila/química , Fluoruracila/farmacologia , Humanos , Derivados da Hipromelose/química , Intestino Grosso/efeitos dos fármacos , Intestino Grosso/metabolismo , Luz , Nanofibras/administração & dosagem , Nanofibras/ultraestrutura , Especificidade de Órgãos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fototerapia/métodos , Ratos Sprague-Dawley , Rosa Bengala/química , Rosa Bengala/efeitos da radiação , Técnicas de Cultura de Tecidos
12.
Int J Pharm ; 559: 289-298, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30707933

RESUMO

In this study, we developed novel thermal and redox-responsive micelles based on the Pluronic F127 tri-block copolymer and employed these for redox-responsive intratumor release of bufalin, an anti-cancer drug. Pluronic F127 was first functionalized with carboxylate groups, and then assembled into micelles. The HOOC-F127-COOH micelles are 20 ±â€¯4 nm in size at 37 °C, but expand to 281 ±â€¯5 nm when cooled to 4 °C. This allows for the free diffusion of bufalin into the micellar cores at low temperatures, while at 37 °C the micelles are much more compact and the drug molecules can be effectively held in their interiors. A high encapsulation efficiency and loading content were obtained via drug incorporation at 4 °C. The drug-loaded micelles were cross-linked with cystamine, which contains a disulfide bond responsive to the local cancer microenvironment. In vitro studies showed that drug release from the cross-linked micelles was low under normal physiological conditions, but markedly accelerated upon exposure to conditions representative of the intracellular tumor environment. Confocal microscopy revealed that the cross-linked micelles gave high levels of drug release inside the cells. In vivo studies in mice showed the drug-loaded cross-linked micelles have potent anti-tumor activity, leading to high levels of apoptosis of tumor cells and significant reductions in tumor volume. The drug-loaded cross-linked micelles did not significantly influence body weight, and there was no evidence for detrimental off-target effects. These results indicate that the Pluronic-based micelles developed in this work are promising drug delivery systems for the targeted treatment of cancer.


Assuntos
Bufanolídeos/química , Poloxâmero/química , Animais , Apoptose/efeitos dos fármacos , Bufanolídeos/administração & dosagem , Linhagem Celular , Linhagem Celular Tumoral , Cistamina/química , Dissulfetos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Camundongos , Camundongos Endogâmicos ICR , Micelas , Tamanho da Partícula , Polímeros/química , Microambiente Tumoral/efeitos dos fármacos
13.
J Colloid Interface Sci ; 539: 433-441, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30599399

RESUMO

Molybdenum disulfide (MoS2)-based drug delivery systems have shown considerable potential in cancer nanomedicines. In this work, a multifunctional nanoplatform comprising MoS2 nanosheets decorated with copper sulfide (CuS) and further functionalized with polyethylene glycol (PEG) is reported. The resultant material has a particle size of approximately 115 nm, and can be loaded with doxorubicin (DOX) to a loading capacity of 162.3 mg DOX per g of carrier. Drug release is triggered by two stimuli (near infrared (NIR) irradiation and pH), and the carrier is shown to have excellent colloidal stability. The presence of both MoS2 and CuS leads to very high photothermal conversion efficiency (higher than with MoS2 alone). In vitro experiments revealed that the blank CuS-MoS2-SH-PEG carrier is biocompatible, but that the synergistic application of chemo-photothermal therapy (in the form of CuS-MoS2-SH-PEG loaded with DOX and NIR irradiation) led to greater cell death than either chemotherapy (CuS-MoS2-SH-PEG(DOX) but no NIR) or photothermal therapy (CuS-MoS2-SH-PEG with NIR). A cellular uptake study demonstrated that the nanoplatform can efficiently enter tumor cells, and that uptake is enhanced when NIR is applied. Overall, the functionalized MoS2 material developed in this work exhibits great potential as an efficient system for dual responsive drug delivery and synergistic chemo-photothermal therapy. The route employed in our work thus provides a strategy to enhance photothermal efficacy for transition metal dichalcogenide drug delivery systems.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Cobre/química , Dissulfetos/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Molibdênio/química , Fototerapia , Antibióticos Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Nanopartículas/química , Tamanho da Partícula , Polietilenoglicóis/química , Relação Estrutura-Atividade , Propriedades de Superfície
14.
Int J Pharm ; 562: 172-179, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30898638

RESUMO

The management of pain and inflammation arising from wounds is essential in obtaining effective healing rates. The application of a wound dressing loaded with an anti-inflammatory drug would enable both issues to be ameliorated, and the aim of this work was to fabricate such a dressing by electrospinning. Fibers comprising ethyl cellulose (EC) and poly(vinyl pyrrolidone) (PVP) loaded with naproxen (Nap) were developed to be used in the early stages of wound care. A family of PVP/EC/Nap systems was prepared by varying the PVP: EC ratio. In all cases, the products of electrospinning comprise non-woven mats of fibers which generally have smooth and cylindrical morphologies. The formulations exist as amorphous solid dispersions, and there appear to be intermolecular interactions between the three components. Adjusting the polymer ratios results in tunable drug release, and formulations have been produced which give zero-order drug release over 20 and 80 h. The fiber mats generated in this work thus have great potential to be used as dressings for the treatment of wound pain and inflammation.


Assuntos
Anti-Inflamatórios não Esteroides/química , Celulose/análogos & derivados , Nanofibras/química , Naproxeno/química , Povidona/química , Celulose/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos
15.
Mater Sci Eng C Mater Biol Appl ; 104: 109917, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500044

RESUMO

In this work, nanofibers based on hydrophilic poly(vinylpyrrolidone) (PVP) and hydrophobic ethyl cellulose (EC) were generated via electrospinning. A model antibiotic, ciprofloxacin (CIF), was also incorporated into the fibers. Fibers were collected on both a foil substrate and a commercial gauze, the latter in the interests of developing a smart fabric. Electron microscopy images revealed that the fibers collected on both foil and fabric were homogeneous and cylindrical. Infrared spectroscopy, X-ray diffraction and differential scanning calorimetry demonstrated that CIF was successfully loaded into the fibers and present in the amorphous physical form. In vitro drug release tests were conducted to simulate drug release from the formulations into a wound site, and as expected the hydrophilic fibers showed much faster release than their hydrophobic analogues. CIF was released through a combined mechanism of polymer erosion and drug diffusion, and the EC nanofibers displayed close to zero-order release over three days. Fibroblast cells are able to grow and proliferate on the fibers. Finally, inhibition zone assays revealed that the growth of both Gram positive and Gram negative bacteria could be effectively inhibited as a result of the presence of CIF in the fibers. There were no marked differences between the fibers collected on foil and on gauze, and electrospinning can be performed directly onto a gauze substrate to prepare a smart fabric.


Assuntos
Bandagens , Celulose/análogos & derivados , Ciprofloxacina/farmacologia , Nanofibras/química , Povidona/química , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Sobrevivência Celular/efeitos dos fármacos , Celulose/química , Derme/citologia , Liberação Controlada de Fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Cinética , Testes de Sensibilidade Microbiana , Nanofibras/ultraestrutura , Difração de Raios X
16.
Bioresour Technol ; 99(17): 7954-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18514511

RESUMO

A novel activated nylon-based membrane was prepared and applied as an adsorbent for the removal of Cu2+ from aqueous solutions. It involved three stages: (i) deposition of a chitosan layer that functionalized the nylon membrane, (ii) cross-linking with epichlorohydrin to stabilize the polymer layer and enabling grafting, and (iii) iminodiacetic acid grafting. SEM and EDX techniques were used to characterize the composition of the membranes. Dynamic adsorption experiments on membranes were carried out at various pH values, contact times, adsorption dosages and initial metal concentrations to determine optimum membrane adsorption properties. The adsorption isotherm relating to Cu2+ fitted the Langmuir equation and an adsorption equilibrium constant and adsorption capacity of 2.345x10(-3)mg/ml and 10.794mg/g were determined, respectively. The experimental data was analyzed using two adsorption kinetic models, pseudo-first-order and pseudo-second-order with the latter system providing the best fit. Finally complete regeneration of the activated nylon membrane was possible using 100mmol/l Na2EDTA.


Assuntos
Cobre/isolamento & purificação , Membranas Artificiais , Nylons/química , Adsorção , Cobre/farmacologia , Recuperação e Remediação Ambiental , Concentração de Íons de Hidrogênio , Cinética , Soluções , Temperatura , Fatores de Tempo , Raios X
17.
J Biomater Appl ; 32(8): 1105-1118, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29295656

RESUMO

Dual-drug-loaded pH-responsive fiber scaffolds were successfully prepared by coaxial electrospinning. These were designed with the aim of being sutured into the resection site after tumor removal, to aid recovery and prevent cancer recurrence. The shell was made up of a mixture of gelatin and sodium bicarbonate (added to provide pH-sensitivity), and was loaded with the anti-inflammatory drug ciprofloxacin; the core comprised poly(lactide-co-ε-caprolactone) with the chemotherapeutic doxorubicin hydrochloride. Scanning electron microscopy revealed most fibers were smooth and homogeneous. Transmission electron microscopy demonstrated the presence of a clear core/shell structure. The fiber scaffolds were further characterized using infrared spectroscopy and X-ray diffraction, which proved that both drugs were present in the fibers in the amorphous form. The gelatin shells were cross-linked with glutaraldehyde to enhance their stability, and water contact angle measurements used to confirm they remained hydrophilic after this process, with angles between 10 and 35°. This is important for onward applications, since a hydrophilic surface is known to encourage cell proliferation. During in vitro drug release studies, a rapid and acid-responsive release of ciprofloxacin was seen, accompanied by sustained and long-term doxorubicin release. Both the release profiles and the mechanical strength of the fibers can effectively be tuned through the sodium bicarbonate content of the fibers: for instance, the break stress varies from 2.00 MPa to 2.57 MPa with an increase in sodium bicarbonate content. The pH values of aqueous media exposed to the scaffolds decrease only slightly, by less than 0.5 pH units, over the two-month timescale, suggesting that only minimal fiber degradation occurs during this time. The fiber scaffolds also have good biocompatibility, as revealed by in vitro cytotoxicity experiments. Overall, our results demonstrate that the novel scaffolds reported here are promising pH-sensitive drug delivery systems, and may be candidates for use after tumor resection surgery.


Assuntos
Preparações de Ação Retardada/química , Gelatina/química , Nanofibras/química , Poliésteres/química , Alicerces Teciduais/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacocinética , Ciprofloxacina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Nanofibras/ultraestrutura , Neoplasias/tratamento farmacológico
18.
Int J Pharm ; 543(1-2): 1-7, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29526623

RESUMO

To prepare temperature and pH dual-responsive drug delivery systems, the thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAAm) was first synthesized by free-radical polymerization. It was then co-dissolved with the pH-sensitive polymer Eudragit® L100-55 (EL100-55) and processed into fibers using electrospinning. Ketoprofen (KET), a model drug, was also incorporated into the composite fibers, and fibers based on a single polymer additionally prepared. The fibers had smooth cylindrical morphologies, and no obvious phase separation could be seen. Using X-ray diffraction, KET was determined to be present in the amorphous state in the fiber matrix. FTIR spectroscopy also indicated the successful incorporation of amorphous KET in the fibers. In vitro drug release studies in media at different pH (4.5 or 7.4) or temperature (25 and 37 °C) showed that the release of KET from the blend PNIPAAm/EL100-55 fibers was dependent both on environmental temperature and pH, reflecting the dual-responsive properties of the fibers. The MTT assay was used to explore the biocompatibility of the PNIPAAm/EL100-55 composite fibers towards L929 fibroblasts. Viability was always found to be >80%, even at polymer concentrations of 100 mg/L. Therefore, the fibers prepared here could lead to the development of multi-responsive materials for drug delivery and tissue engineering.


Assuntos
Sistemas de Liberação de Medicamentos , Nanofibras/administração & dosagem , Nanofibras/química , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Camundongos , Tecnologia Farmacêutica
19.
Colloids Surf B Biointerfaces ; 171: 142-149, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30025376

RESUMO

We report a dual-responsive drug delivery system prepared by electrospinning. Blend fibers of poly(N-vinylcaprolactam) (PNVCL) and ethyl cellulose (EC) were first prepared, with the aim of developing thermoresponsive sustained release formulations. Eudragit L100-based fibers were then generated to yield pH-sensitive materials. Attempts to produce three-polymer fibers of EC, PNVCL and Eudragit were unsuccessful, and therefore hybrid mats containing two fiber populations (one made of PNVCL/EC, one comprising Eudragit) were instead fabricated by twin-jet electrospinning. Analogous drug-loaded versions of all the formulations were also prepared containing ketoprofen (KET). The fibers were largely smooth and homogeneous, and the addition of KET did not affect their morphology. The PNVCL-containing fiber mats changed from being hydrophilic to hydrophobic when the temperature was increased through the lower critical solution temperature of 33 °C. In vitro drug release profiles showed that the hybrid fiber mats were able to combine the properties of the three polymers, exhibiting both pH-sensitive and thermosensitive properties with sustained release. In addition, they were found to be nontoxic and suitable for cell growth. This study therefore demonstrates that PNVCL/EC/KET-Eudragit/KET multicomponent fiber mats comprise effective and biocompatible materials for targeted drug delivery.


Assuntos
Nanofibras/química , Nanotecnologia , Ácidos Polimetacrílicos/síntese química , Temperatura , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Ácidos Polimetacrílicos/química , Propriedades de Superfície
20.
ACS Appl Mater Interfaces ; 10(49): 42115-42126, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30462492

RESUMO

Noninvasive physical treatment with relatively low intensity stimulation and the development of highly efficient anticancer medical strategy are still desirable for cancer therapy. Herein a versatile, biodegradable, hollow mesoporous organosilica nanocapsule (HMONs) nanoplatform that is capped by the gemcitabine (Gem) molecule through a pH-sensitive acetal covalent bond is designed. The fabricated nanocapsule exhibits desirable small molecule release at the tumor tissues/cell sites and shows a reduced risk for drug accumulation. After loading indocyanine green (ICG), the heat-shock protein 90 (Hsp 90) inhibitor, and 17AAG and modification with polyethylene glycol (NH2-PEG), the resulting ICG-17AAG@HMONs-Gem-PEG exhibited a precisely controlled release of ICG and 17AAG and low-temperature photothermal therapy (PTT) (∼41 °C) with excellent tumor destruction efficacy. In addition, ICG loading conferred the nanoplatform with near-infrared fluorescence imaging (FL) and photoaccoustic (PA) imaging capability. In short, this work not only presents a smart drug self-controlled nanoplatform with pH-responsive payload release and theranostic performance but also provides an outstanding low-temperature PTT strategy, which is highly valid in the inhibition of cancer cells with minimal damage to the organism. Therefore, this research provides a paradigm that has a chemodrug-gated HMONs-based theranostic nanoplatform with intrinsic biodegradability, multimodal imaging capacity, high low-temperature PTT/chemotherapy efficacy, and reduced systemic toxicity.


Assuntos
Doxorrubicina , Hipertermia Induzida , Verde de Indocianina , Nanocápsulas , Compostos de Organossilício , Fototerapia , Animais , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Camundongos , Camundongos Nus , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Compostos de Organossilício/química , Compostos de Organossilício/farmacocinética , Compostos de Organossilício/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia
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