The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer

Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from N α ,N ε -dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy.

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“…It is a measurement of cell metabolic activity, and correlates quite well with cell proliferation [25].…”

Section: Cytotoxicity Assays -Antitumor Activity Of Mtxmentioning

confidence: 98%

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

et al. 2013

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“…was measured at 560 nm by plate reader (Biorad, Hercules, CA). Cellular uptake studies in C6 rat glioma cells Cellular uptake study was performed to evaluate cellular localization of DTX-loaded fluorescent liposome in C6 rat glioma cell line (Venkatesan et al, 2011). In brief, C6 cells were seeded (3 Â 10 4 ) and grown on poly-L-lysine coated cover slips.…”

Section: In Vitro Cell Viability Assaymentioning

confidence: 99%

Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor

et al. 2017

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Docetaxel (DTX) is found to be very effective against glioma cell in vitro. However, in vivo passage of DTX through BBB is extremely difficult due to the physicochemical and pharmacological characteristics of the drug. No existing formulation is successful in this aspect. Hence, in this study, effort was made to send DTX through blood-brain barrier (BBB) to brain to treat diseases such as solid tumor of brain (glioma) by developing DTX-loaded nanoliposomes. Primarily drug-excipients interaction was evaluated by FTIR spectroscopy. The DTX-loaded nanoliposomes (L-DTX) were prepared by lipid layer hydration technique and characterized physicochemically. In vitro cellular uptake in C6 glioma cells was investigated. FTIR data show that the selected drug and excipients were chemically compatible. The unilamellar vesicle size was less than 50 nm with smooth surface. Drug released slowly from L-DTX in vitro in a sustained manner. The pharmacokinetic data shows more extended action of DTX from L-DTX in experimental rats than the free-drug and Taxotere Õ . DTX from L-DTX enhanced 100% drug concentration in brain as compared with Taxotere Õ in 4 h. Thus, nanoliposomes as vehicle may be an encouraging strategy to treat glioma with DTX.

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“…Las terapias antiangiogénicas actuales buscan inhibirlos con el fin de disminuir la neovascularización, apoptosis y metástasis. Estos puede ser suprimidos por múltiples agentes entre ellos los inhibidores selectivos de la COX-2, tal como el celecoxib, importante agente anti-inflamatorio (Venkatesan et al, 2011), que se encuentra bajo estudio para el tratamiento de variados tumores malignos tales como cáncer colorectal, cáncer de mama, pulmón y próstata (Amrite et al).…”

Section: Discussionunclassified

Efecto Antimetastásico de Celecoxib/PLGA en un Modelo Murino de Adenocarcinoma Mamario TA3-MTX-R

et al. 2015

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RESUMEN: La metástasis es el proceso de propagación de un foco cancerígeno a un órgano distinto de aquel en que se inició; ocurriendo generalmente por vía sanguínea o linfática. La localización más frecuentes de las metástasis son los órganos más irrigados como el cerebro, pulmones, hígado, huesos y glándulas suprarrenales. El objetivo fue analizar el patrón de metástasis hepática de tumor TA3-MTX-R, luego de la aplicación del antiangiogénico Celecoxib microencapsulado en PLGA en ratones, así como la disminución de áreas metastásicas a nivel lobulillar. Se utilizó un modelo de tumor experimental, inducido por células TA3-MTX-R, en 18 ratones, separados en 3 grupos de 6 animales, los cuales fueron tratados con dos presentaciones de Celecoxib en administración intramuscular (Grupo 1, Control: TA3-MTX-R; Grupo 2: TA3-MTX-R+Cx y Grupo 3: TA3-MTX-R+Cx/PLGA). Los ratones fueron sacrificados y procesados histológicamente para ser teñidos con H&E y Tricrómico de Arteta. El estudio reveló que el higado muestra una marcada heterogeneidad, y un patrón de metástasis perivascular y neovascularización central y periférica. Además, Celecoxib redujo significativamente la invasión tumoral en el hígado (p<0,0001). Los resultados son similares a descripciones parciales realizadas previamente y son comparables a otras líneas tumorales. Creemos que la vía de administración del fármaco es crítica para la interpretación de los resultados. Los hallazgos son importantes para la discusión de otras investigaciones en donde Celecoxib es usado como un fármaco antiangiogénico.

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The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer

Cited by 229 publications

References 49 publications

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor

Efecto Antimetastásico de Celecoxib/PLGA en un Modelo Murino de Adenocarcinoma Mamario TA3-MTX-R

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