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1.
Appl Biochem Biotechnol ; 195(1): 51-67, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35932371

RESUMO

This study aimed to evaluate the potential of mesenchymal stem cell-derived exosomes loaded with curcumin (Curc-Exos) as an effective therapeutic strategy for rheumatoid arthritis through modulation of proliferation and inflammatory response in HIG-82 synovial cells. For this purpose, Exos were isolated and characterized with BCA protein assay, DLS, FE-SEM, and TEM. The Curc was embedded by mixing it with Exos in a 1:4 ratio. It was found that the Curc stability has improved after loading on Exos compared to the free Curc. Besides, the in vitro studies using LPS-stimulated HIG-82 synovial cells indicated the efficiency of Curc-Exos in enhancing cytotoxicity and apoptosis compared to the free Curc treatment. It was also revealed that Curc-Exos significantly could reduce the expression levels of anti-apoptotic proteins IAP1 and IAP2 and inflammatory mediators including IL-6, TNF-α, MMP1, and PGE2. This preliminary study confirmed the suitability of Curc-Exos in counteracting the proliferation and inflammatory response of rheumatoid arthritis synovial fibroblasts in vitro.


Assuntos
Artrite Reumatoide , Curcumina , Exossomos , Células-Tronco Mesenquimais , Sinoviócitos , Humanos , Exossomos/metabolismo , Sinoviócitos/metabolismo , Curcumina/farmacologia , Curcumina/metabolismo , Artrite Reumatoide/terapia , Artrite Reumatoide/metabolismo , Proliferação de Células , Células-Tronco Mesenquimais/metabolismo , Fibroblastos/metabolismo
2.
J Biomed Mater Res A ; 110(2): 316-330, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34378328

RESUMO

Electrospun nanofibers (NFs)-based drug delivery approaches are of particular interest as a hopeful implantable nanoplatform for localized cancer therapy and treating tissue defect after resection, allowing the on-site drug delivery with minimal side effect to healthy cells. To maintain therapeutic concentrations of anticancer molecules for a relatively long time through a combination of burst and sustained drug release mechanisms, a hybrid of polycaprolactone and gelatin (PCL/GEL) was used for co-encapsulation of free curcumin (CUR) and CUR-loaded mesoporous silica nanoparticles (CUR@MSNs) via electrospinning, resulting in a novel drug-loaded nanofibrous scaffold, CUR/CUR@MSNs-NFs. The as-prepared MSNs and composite NFs were characterized via TGA, FTIR, FE-SEM, TEM, and BET. In vitro release profile of CUR from CUR/CUR@MSNs-NFs was examined, and the in vitro antitumor efficacy against MDA-MB-231 breast cancer cells was also evaluated through MTT, scratch assay, DAPI staining, and real-time PCR. The results disclosed that the smooth, bead-free, and randomly oriented CUR/CUR@MSNs-NFs displayed a combination of initial rapid discharge and sustained release for CUR, which led to higher cytotoxicity, lower migration as well as a more pronounced effect on apoptosis induction than CUR-NFs and CUR@MSNs-NFs. The present study illustrated that the dual drug release mechanisms through MSN/NF-mediated drug delivery systems might have a highly hopeful application as a localized implantable scaffold for potential postoperative breast cancer therapy.


Assuntos
Curcumina , Nanofibras , Nanopartículas , Curcumina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Dióxido de Silício
4.
Artif Cells Nanomed Biotechnol ; 45(8): 1649-1656, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28078913

RESUMO

Nanoparticle-based targeted drug delivery has the potential for rendering silibinin specifically at the favorite site using an external magnetic field. Also, it can circumvent the pitfalls of poor solubility. For this purpose, silibinin-loaded magnetic nanoparticles are fabricated, characterized and evaluated cytotoxicity and hTERT gene expression in A549 lung cancer cell line. silibinin-loaded PLGA-PEG-Fe3O4 had dose- and time-dependent cytotoxicity than pure silibinin. Additionally, hTERT expression is more efficiently reduced with increasing concentrations of nanosilibinin than pure silibinin. The present study indicates that PLGA-PEG-Fe3O4 nanoparticles, as an effective targeted carrier, can make a promising horizon in targeted lung cancer therapy.


Assuntos
Portadores de Fármacos/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Nanopartículas de Magnetita/química , Silimarina/química , Silimarina/farmacologia , Telomerase/genética , Células A549 , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Ácido Láctico/química , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Silibina
5.
Bioimpacts ; 3(2): 67-74, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23878789

RESUMO

Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results : Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

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