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1.
Pharm Res ; 36(10): 149, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420752

RESUMO

PURPOSE: Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS: Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP). RESULTS: Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC50 of 1.94 ± 0.22 and 1.02 ± 0.36 µM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration. CONCLUSION: The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies.


Assuntos
Antineoplásicos/administração & dosagem , Berberina/administração & dosagem , Doxorrubicina/administração & dosagem , Nanocápsulas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Berberina/farmacocinética , Berberina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Interações de Medicamentos , Liberação Controlada de Fármacos , Humanos , Masculino , Ratos Sprague-Dawley
2.
Pharm Res ; 36(10): 140, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31367876

RESUMO

PURPOSE: In order to overcome the obstacles and side effects of classical chemotherapy, numerous studies have been performed to develop the treatment based on targeted transport of active compounds directly to the site of action. Since tumor cells are featured with intensified glucose metabolism, we set out to develop innovative, glucose-modified PAMAM dendrimer for the delivery of doxorubicin to breast cancer cells. METHODS: PAMAM-dox-glc conjugate was synthesized and characterized by 1H NMR, FT-IR, size and zeta potential measurements. The drug release rate from conjugate was evaluated by dialysis under different pH conditions. The expression level of GLUT family receptors in cells cultured in full and glucose-deprived medium was evaluated by quantitative real-time RT-PCR and flow cytometry. The cytotoxicity of conjugate in presence or absence of GLUT1 inhibitors was determined by MTT assay. RESULTS: We showed that PAMAM-dox-glc conjugate exhibits pH-dependent drug release and increased cytotoxic activity compared to free drug in cells cultured in medium without glucose. Further, we proved that these cells overexpress transporters of GLUT family. The toxic effect of conjugate was eliminated by the application of specific GLUT1 inhibitors. CONCLUSION: Our findings revealed that the glucose moiety plays a crucial role in the recognition of cells with high expression of GLUT receptors. By selectively blocking GLUT1 transporter we showed its importance for the cytotoxic activity of PAMAM-dox-glc conjugate. These results suggest that PAMAM-glucose formulations may constitute an efficient platform for the specific delivery of anticancer drugs to tumor cells overexpressing transporters of GLUT family.


Assuntos
Antineoplásicos/farmacologia , Dendrímeros/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Transportador de Glucose Tipo 1/metabolismo , Glucose/efeitos adversos , Antineoplásicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Regulação da Expressão Gênica , Glucose/química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Tamanho da Partícula
3.
Anticancer Res ; 39(8): 4079-4084, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366491

RESUMO

BACKGROUND/AIM: Recurrent osteosarcoma is a recalcitrant disease; therefore, an improved strategy is urgently needed to provide therapy. In order to develop a novel strategy for this disease, our lab has developed a patient-derived orthotopic xenograft (PDOX) mouse model for osteosarcoma. The combination of sorafenib (SFN) and palbociclib (PAL) was shown to be effective of hepatocellular carcinoma. However, whether this combination is efficacious on osteosarcoma has not been reported. The aim of this study was to determine the efficacy of the SFN and PAL combination on a cisplatinum (CDDP)-resistant osteosarcoma PDOX model. MATERIALS AND METHODS: Osteosarcoma PDOX models were randomly divided into five treatment groups: untreated-control, CDDP, SFN, PAL and the combination of SFN and PAL. RESULTS: Of these agents, the SFN-PAL combination significantly regressed tumor growth, and enhanced tumor necrosis with degenerative changes in the osteosarcoma PDOX. CONCLUSION: The SFN-PAL combination is an effective treatment strategy for osteosarcoma and therefore holds promise for clinical efficacy.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Osteossarcoma/tratamento farmacológico , Piperazinas/administração & dosagem , Piridinas/administração & dosagem , Sorafenibe/administração & dosagem , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Humanos , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Osteossarcoma/genética , Osteossarcoma/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Anticancer Res ; 39(8): 4379-4383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366533

RESUMO

BACKGROUND/AIM: Dose-dense doxorubicin and cyclophosphamide (ddAC) followed by dose-dense paclitaxel (ddP) (ddAC-P) has improved disease-free survival of patients with breast cancer. The aim of this study was to evaluate the safety and relative dose intensity (RDI) of ddAC-P administered together with pegfilgrastim. PATIENTS AND METHODS: Between May 2015 and Aug 2017, 44 patients were retrospectively reviewed; they were administered 4 cycles of ddAC, followed by 4 cycles of ddP. Pegfilgrastim (3.6 mg) was administered in every cycle. RESULTS: The mean RDIs for ddAC-P, ddAC, and ddP were 95.0%, 94.5%, and 93.3%, respectively. The prevalence of high RDIs (≥85%) for ddAC-P, ddAC, and ddP was 90.9%, 84.1%, and 88.6%, respectively. Seven of the 10 patients with low RDIs experienced grade 1 or 2 fever. CONCLUSION: DdAC-P administered together with pegfilgrastim (3.6 mg) appears to be feasible and maintains RDI in most of Japanese patients with breast cancer. Rapid evaluation and proper management of fever may prevent low RDI.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/patologia , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Feminino , Filgrastim/administração & dosagem , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Polietilenoglicóis/administração & dosagem
6.
Biomater Sci ; 7(9): 3898-3905, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31317137

RESUMO

To target a response to a high oxidative stress environment of inflammatory or tumor sites, various reactive oxygen species (ROS) sensitive polymers have been developed as drug delivery systems. In this study, a novel oxidation sensitive copolymer, phenylboronic acid pinacol ester-functionalized methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), was designed and synthesized by ring-opening alternating copolymerization (ROAP) and click reaction. The copolymers could self-assemble into micelles in aqueous solution with an average size of 20.3 ± 9.3 nm, and are able to load hydrophobic anticancer drug (doxorubicin, DOX) with a high encapsulation efficiency of 75.2%. Interestingly, the encapsulated drug showed accelerated release in the trigger of H2O2, or at low pH values. The copolymers have low cytotoxicity indicated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay towards 4T1 cells, which showed cell viabilities of more than 80% with treatment of our copolymers at concentrations up to 0.5 mg mL-1. The effective uptake of the drug-loaded micelles by 4T1 cells was investigated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) analysis. Finally, compared with free DOX, the DOX-loaded nanoparticles exhibited a better antitumor effect and had lower systemic toxicity in 4T1 tumor-bearing mice. Therefore, this new kind of copolymer acting as a stimuli-responsive nanocarrier should represent a promising therapeutic platform for cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Ácidos Borônicos/química , Doxorrubicina/administração & dosagem , Nanocápsulas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Ésteres/química , Humanos , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Oxirredução , Polietilenoglicóis/química
7.
J Nanobiotechnology ; 17(1): 83, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291948

RESUMO

BACKGROUND: Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO. RESULTS: At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo. CONCLUSIONS: The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.


Assuntos
Antineoplásicos/química , Materiais Biomiméticos/química , Portadores de Fármacos/química , Macrófagos/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Liberação Controlada de Fármacos , Grafite/química , Humanos , Hipertermia Induzida , Raios Infravermelhos , Lasers , Masculino , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Polietilenoimina/química , Distribuição Tecidual
8.
Chem Commun (Camb) ; 55(61): 9015-9018, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31290867
9.
Carbohydr Polym ; 219: 143-154, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151511

RESUMO

In recent years, the utilization of polysaccharides as targeted drug carriers has attracted considerable attention. Herein, Angelica sinensis polysaccharide (ASP), a plant polysaccharide with good biocompatibility, excellent aqueous solubility and intrinsic liver-targeted capability, was modified with hydrophobic group (deoxycholic acid) to fabricate amphiphilic conjugate (ASP-DOCA). Self-assembled nanoparticles were successfully developed for hepatoma-targeted delivery of therapeutic drug doxorubicin (DOX). The DOX loaded nanoparticles (DOX/ASP-DOCA NPs) were spherical in shape with a particle size of 228 nm and negatively charged around -17 mV. DOX was released from nanoparticles in a sustainable and pH-dependent manner. In vitro cellular uptake revealed that DOX/ASP-DOCA NPs were internalized into HepG2 cells through asialoglycoprotein receptor (ASGPR)-mediated endocytosis, resulting in a higher anti-proliferation effect than DOX-loaded dextran derivative DOX/DEX-DOCA NPs. Additionally, DOX/ASP-DOCA NPs showed higher inhibition on the growth of HepG2 multicellular spheroids (MCs) than DOX/DEX-DOCA NPs. In vivo imaging demonstrated that ASP-DOCA NPs specifically targeted HepG2 tumors via ASGPR, improving the accumulation of DOX/ASP-DOCA NPs in tumors and generating superior antitumor activity compared with free DOX and DOX/DEX-DOCA NPs. Taken together, ASP-DOCA NPs possess potential applications in drug delivery systems targeting liver cancer.


Assuntos
Angelica sinensis/metabolismo , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Nanoconjugados/uso terapêutico , Nanopartículas/uso terapêutico , Polissacarídeos/uso terapêutico , Animais , Receptor de Asialoglicoproteína/metabolismo , Ácido Desoxicólico/química , Células HeLa , Células Hep G2 , Humanos , Camundongos , Nanopartículas/ultraestrutura , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
10.
Phys Chem Chem Phys ; 21(27): 15222-15232, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31250877

RESUMO

Star-shaped polymers have received significant attention and have been widely developed for prospective applications in drug delivery owing to their topological structure and unique physiochemical characteristics. The anticancer drug doxorubicin (DOX) was used as a model drug, and four/six-arm star-shaped block polymeric micelles were employed as the carriers. The dissipative particle dynamics (DPD) method was adopted to simulate the formation of micelles, the effects of the hydrophobic/hydrophilic block ratio on the micellar structure and drug-loading performance, the effect of the drug loading content on the micellar morphology, and the effect of the pH-sensitive block ratio on the drug release properties. Under neutral conditions (pH = 7.4), increasing the hydrophobic block ratio reduces the stability of the micelle structure but could improve its drug loading performance. Increasing the pH-sensitive block (DEAEMA) ratio is beneficial to the drug loading performance of the mikto-arm star-shaped polymeric micelles and is detrimental to the drug loading performance of the herto-arm star-shaped polymeric micelles. After comparing the structural changes, radial distribution function (RDF) and mean square displacement (MSD) of the polymeric micelles with different pH-sensitive block ratios under weakly acidic conditions (pH = 5.0), the drug release properties of the drug-loaded micelles were systematically analysed. The results showed that the higher the proportion of the pH-sensitive block in the polymeric micelles, the better their pH-response performance, and the looser the structure of the micelles during the release process. A too high or too low ratio of pH-sensitive blocks in the polymeric micelles was detrimental to drug release performance. This study could provide theoretical support for the structural design and development of novel functional block polymers.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Micelas , Simulação de Dinâmica Molecular , Antineoplásicos/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/química , Concentração de Íons de Hidrogênio , Polímeros/química
11.
Stud Health Technol Inform ; 261: 261-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156127

RESUMO

Over 85% of human cancers are solid tumors. The effectiveness of anticancer therapy in solid tumors depends on adequate delivery of the therapeutic agent to tumor cells. Inadequate delivery would result in residual tumor cells, which in turn would lead to regrowth of tumors and possibly development of resistant cells. The most prominent option, for now, is the local delivery of chemotherapic drugs into the cavity resection of the tumor. However, the burst release of massive concentrations of the drugs usually boosts the side effects of chemotherapy. Aiming to block the burst release a new drug delivery system (DDS) for the local delivery of Doxorubicin (DOX) was designed and tested, combining different materials and techniques. Following a bottom-up approach, porous spherical calcium carbonate (CaCO3) microspheres, with high loading properties, were loaded with DOX and Layer by Layer (LbL) assembled by biocompatible and biodegradable polyelectrolytes, dextran sodium sulfate (DSS) and polyarginine (PARG). Then, a protocol for the fabrication of alginate (Alg) hydrogels associated with LbL coated drug loaded CaCO3 microspheres were developed by combining internal and external gelation. Therefore, injectable multicompartment hydrogels (MCH) for the local and sustained delivery of chemotherapeutic drugs, with the ability to block the burst release, were developed and characterized.


Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Hidrogéis , Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos
12.
Medicine (Baltimore) ; 98(25): e15873, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232921

RESUMO

RATIONALE: Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study. PATIENTS CONCERNS: This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung). DIAGNOSES: The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes. INTERVENTIONS: The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles. OUTCOMES: The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months. LESSONS: Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.


Assuntos
Ameloblastoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Maxilomandibulares/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/uso terapêutico , Neoplasias Maxilomandibulares/diagnóstico por imagem , Neoplasias Maxilomandibulares/patologia , Neoplasias Pulmonares/secundário , Mesna/administração & dosagem , Mesna/uso terapêutico , Metástase Neoplásica , Resultado do Tratamento
13.
Int J Nanomedicine ; 14: 3361-3373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190797

RESUMO

Purpose: To fabricate multifunctional nanocapsule via Pickering emulsion route to facilitate tumor-targeted delivery. Methods: Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles (PNA) stabilized nanocapsules were fabricated by Pickering emulsion (PE) technology. For controllable drug-release and enhancing targeted antitumor effects, the nanocapsules were crosslinked with cystamine and coupled on cell-surface molecule markers (cRGDfK) to achieve on-demand drug release and targeted delivery. Results: The fabricated PE and nanocapsules with average particle sizes (250 and 150 nm) were obtained. Encapsulation efficiency of hydrophobic anticancer drug (DOX) was determined as >90%. Release kinetic profiles for encapsulated nanocapsules displayed circulation stability and redox-sensitive releasing behavior with the supposed increase bioavailability. Both cytotoxicity assay, cellular uptake analysis and anticancer efficacy in B16F10 murine model demonstrated these redox-responsive drug-release and active targeted delivery. Conclusion: The results clearly demonstrated nanocapsule via PE route as promising candidate to provide an effective platform for incorporating hydrophobic drug for targeted cancer chemotherapy.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/química , Resinas Acrílicas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular , Reagentes para Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanocápsulas/ultraestrutura , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoimina/química
14.
Int J Nanomedicine ; 14: 3557-3569, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190812

RESUMO

Purpose: Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment. Methods: The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin 'two in one' nanocarriers. Results: We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression. Conclusion: Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , RNA Interferente Pequeno/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Inativação Gênica , Humanos , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , RNA Interferente Pequeno/genética , Dióxido de Silício/química
15.
Int J Nanomedicine ; 14: 3615-3627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190815

RESUMO

Purpose: Modified top-down procedure was successfully employed in the synthesis of aragonite nanoparticles (NPs) from cheaply available natural seawater cockle shells. This was with the aim of developing a pH-sensitive nano-carrier for effective delivery of doxorubicin (DOX) on MCF-7 breast cancer cell line. Methods: The shells were cleaned with banana pelts, ground using a mortar and pestle, and stirred vigorously on a rotary pulverizing blending machine in dodecyl dimethyl betane solution. This simple procedure avoids the use of stringent temperatures and unsafe chemicals associated with NP production. The synthesized NPs were loaded with DOX to form DOX-NPs. The free and DOX-loaded NPs were characterized for physicochemical properties using field emission scanning electron microscopy, transmission electron microscopy, zeta potential analysis, Fourier transform infrared spectroscopy, and X-ray diffraction. The release profile, cytotoxicity, and cell uptake were evaluated. Results: NPs had an average diameter of 35.50 nm, 19.3% loading content, 97% encapsulation efficiency, and a surface potential and intensity of 19.1±3.9 mV and 100%, respectively. A slow and sustained pH-specific controlled discharge profile of DOX from DOX-NPs was observed, clearly showing apoptosis/necrosis induced by DOX-NPs through endocytosis. The DOX-NPs had IC50 values 1.829, 0.902, and 1.0377 µg/mL at 24, 48, and 72 hrs, while those of DOX alone were 0.475, 0.2483, and 0.0723 µg/mL, respectively. However, even at higher concentration, no apparent toxicity was observed with the NPs, revealing their compatibility with MCF-7 cells with a viability of 92%. Conclusions: The modified method of NPs synthesis suggests the tremendous potential of the NPs as pH-sensitive nano-carriers in cancer management because of their pH targeting ability toward cancerous cells.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Carbonato de Cálcio/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Musa/química , Nanopartículas/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Difração de Raios X
16.
Ann Hematol ; 98(9): 2121-2129, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240469

RESUMO

We retrospectively analyzed 70 patients with classical Hodgkin lymphoma (cHL) who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy to assess the influence of the soluble interleukin-2 receptor (sIL-2R) level at diagnosis on the clinical outcome. Receiver operating characteristic analyses determined that the optimal cutoff value of the sIL-2R level for progression-free survival (PFS) was 2490 U/mL. Using this cutoff value, patients were classified into low (n = 46) and high (n = 24) sIL-2R groups. The patients in the high sIL-2R group exhibited a significantly inferior PFS (44.1% vs. 90.4% at 5 years, P < 0.001) and overall survival (OS) (67.6% vs. 94.7% at 5 years, P = 0.001) compared with those in the low sIL-2R group. Multivariate analysis showed that a high sIL-2R level was an independent prognostic factor for PFS after adjusting for stage, white blood cell, hemoglobin, and B symptoms, and also OS after adjusting for age and stage (hazard ratio (HR) 6.49, P < 0.001 and HR 5.98, P = 0.009, respectively). In patients with advanced-stage cHL, a high sIL-2R level predicted 5-year PFS even after adjustment for international prognostic score > 4 (HR 6.00, P = 0.007). These results demonstrate that the sIL-2R level can be a useful prognostic factor in patients with cHL treated with ABVD with or without radiotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiorradioterapia , Doença de Hodgkin , Proteínas de Neoplasias/sangue , Receptores de Interleucina-2/sangue , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Vimblastina/administração & dosagem
17.
Pharm Res ; 36(8): 115, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161432

RESUMO

PURPOSE: Fibrin gels (FBGs) are potential delivery vehicles for many drugs, and can be easily prepared from purified components. We previously demonstrated their applicability for the release of different doxorubicin (Dox) nanoparticles used clinically or in an experimental stage, such as its inclusion complex with the amino ß-cyclodextrin polymer (oCD-NH2/Dox). Here we extend these studies by in vitro and in vivo evaluations. METHODS: An in vitro cytotoxicity model consisting of an overlay of a neuroblastoma (NB) cell-containing agar layer above a drug-loaded FBG layer was used. Local toxicity in vivo (histology and blood analysis) was studied in a mouse orthotopic NB model (SHSY5YLuc+ cells implanted into the left adrenal gland). RESULTS: In vitro data show that FBGs loaded with oCD-NH2/Dox have a slightly lower cytotoxicity against NB cell lines than those loaded with Dox. Fibrinogen (FG), and Ca2+ concentrations may modify this activity. In vivo data support a lower general and local toxicity for FBGs loaded with oCD-NH2/Dox than those loaded with Dox. CONCLUSION: Our results suggest a possible increase of the therapeutic index of Dox when locally administered through FBGs loaded with oCD-NH2/Dox, opening the possibility of using these releasing systems for the treatment of neuroblastoma.


Assuntos
Antineoplásicos/farmacologia , Celulose/química , Ciclodextrinas/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Fibrina/química , Nanopartículas/química , Neuroblastoma/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/sangue , Portadores de Fármacos/toxicidade , Feminino , Géis , Xenoenxertos , Humanos , Camundongos Nus , Nanopartículas/toxicidade
18.
Anticancer Res ; 39(6): 3071-3077, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177151

RESUMO

BACKGROUND: To compare outcomes for patients with colorectal cancer liver metastases (CRCLM) treated by drug-eluting bead chemoembolization (DEB-TACE) or radioembolization (TARE). PATIENTS AND METHODS: A single-center retrospective review was carried out on 202 patients with CRCLM, treated by DEB-TACE (n=47) or TARE (n=155) patients. Propensity-matching yielded 44 pairs. Paired statistical analysis was performed on matched pair demographics, treatment response, and survival. RESULTS: Patients treated with DEB-TACE had worse extra-hepatic metastasis (68.1 vs. 47.7%, p=0.014) and ≥10 liver lesions (42.2 vs. 68.8%, p=0.001). Matched patients treated with DEB-TACE had a trend towards worse toxicity (27% vs. 9.1% (p=0.057). Index DEB-TACE treatment was not a prognostic factor for overall survival (hazard ratio=0.94, 95% confidence intervaI=0.54-1.65; p=0.83). CONCLUSION: In the matched CRCLM cohort, there was a trend towards worse toxicity post-DEB-TACE treatment, but it was not an independent prognostic factor for survival.


Assuntos
Antineoplásicos/administração & dosagem , Quimioembolização Terapêutica/métodos , Neoplasias Colorretais/patologia , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Irinotecano/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Antineoplásicos/efeitos adversos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Neoplasias Colorretais/mortalidade , Progressão da Doença , Doxorrubicina/efeitos adversos , Feminino , Humanos , Irinotecano/efeitos adversos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
19.
Pan Afr Med J ; 32: 42, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31143347

RESUMO

Peripheral neuroectodermal tumors (PNET) of the kidney are extremely rare. They are often diagnosed at a late stage due to their nonspecific clinical presentation. Treatment of patients with metastases is based on palliative chemotherapy. We here report a case of PNET of the kidney with sudden onset of metastases to the lymph nodes and to the skin. The patient showed good clinical and radiological response and experienced progression-free survival at 6 years after polychemotherapy with vincristine, doxorubicin and cyclophosphamide.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos Periféricos/tratamento farmacológico , Adulto , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Humanos , Neoplasias Renais/patologia , Metástase Linfática/patologia , Masculino , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Neoplasias Cutâneas/secundário , Vincristina/administração & dosagem
20.
J Colloid Interface Sci ; 551: 1-9, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071490

RESUMO

Ultrasound-responsive chemistry was exploited in manufacture of drug delivery nanoparticulates for pursuit of on-demand ultrasound-stimulated drug release function. In principle, the ultrasound-labile oxyl-alkylhydroxylamine (-oa-) linkage was tailored between the segments of amphiphiles. Consequently, the hydrophobic chemotherapeutic doxorubicin could be readily assembled with the hydrophobic segments of amphiphiles into interior compartments, whereas the hydrophilic segments represented as the external surroundings. Upon ultrasonication, the proposed phase-segregated self-assemblies were determined to be subjected to evident structural rearrangement as a consequence of -oa- cleavage. Simultaneously, the release rate of doxorubicin payloads appeared to accelerate due to the ultrasound-induced structural destabilization, consequently eliciting potent cytotoxic efficacy at the affected cells. Another noteworthy characteristic of the proposed self-assemblies was poly (lactobionamidoethyl methacrylate) (pLAMA) as the hydrophilic components of the amphiphiles, characterized to possess galactosylated residues. In view of the specific affinity of galactosylated residues (and lactosylated residues) to asialoglycoprotein receptors (overexpressed on the surface of intractable hepatocellular carcinoma), the proposed self-assemblies were determined to impart preferential affinities to hepatocellular carcinoma. Together with the strategic ultrasound-stimulated drug release property, our proposed drug delivery system demonstrated appreciably pharmaceutical efficacy on hepatocellular carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Portadores de Fármacos/química , Hidroxilaminas/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Ácidos Polimetacrílicos/química , Ondas Ultrassônicas , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Galactose/química , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Polimerização
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