Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment

Sesărman, Alina; Tefas, Lucia Ruxandra; Sylvester, Bianca; Licărete, Emilia; Rauca, Valentin Florian; Lupuţ, Lavinia; Pătraș, Laura; Porav, Sebastian; Banciu, Manuela; Porfire, Alina

doi:10.1007/s13346-018-00598-8

Cited by 63 publications

(39 citation statements)

References 41 publications

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“…As a parenteral dosage form, liposomal products must be sterile, pyrogen free, and well tolerated [24]. The lack of hemolytic activity is also mentioned as requirement for liposome products [25].…”

Section: Defining the Qtpp For Liposomal Products And Identification mentioning

confidence: 99%

Pharmaceutical Development of Liposomes Using the QbD Approach

Porfire¹,

Achim²,

Barbălată³

et al. 2019

Liposomes - Advances and Perspectives

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Quality by Design (QbD) is a systematic, risk-based approach to pharmaceutical product and manufacturing development, which uses quality-improving scientific methods upstream in the research, development, and design phases, in order to assure that quality and safety are designed into product at as early stage as possible. This work focuses on the state-of-the-art applications of the QbD principles in the development of liposomes. The QbD approach has recently been proposed as a useful tool to obtain higher-quality liposomal products, as their development is a challenging task, involving intricate formulation and manufacturing processes. Thus, the current strategies to define the relationship between the critical material attributes or process parameters and product critical quality attributes and to establish the design space are overviewed. Additionally, the current characterization methodologies are described, as part of the control strategy required within the QbD paradigm.

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Section: Defining the Qtpp For Liposomal Products And Identification mentioning

confidence: 99%

Pharmaceutical Development of Liposomes Using the QbD Approach

Porfire¹,

Achim²,

Barbălată³

et al. 2019

Liposomes - Advances and Perspectives

Self Cite

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“…To evaluate the activity of MMP‐2 activity from tumor lysates prepared in nonreducing conditions, 20 µg proteins were separated on 0.1% gelatin and 7.5% acrylamide electrophoretic gels under denaturing conditions, as previously described . After gels were stained with Coomassie blue, 2 major areas of gelatinolytic activity were revealed on the zymographic gels, at 62 kDa (corresponding to the active form of MMP‐2) and 72 kDa (corresponding to zymogen form of MMP‐2, pro‐MMP‐2).…”

Section: Methodsmentioning

confidence: 99%

Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5‐fluorouracil in vivo

et al. 2020

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5-Fluorouracil-based therapy remains the main approach in colorectal cancer, even though there are still some drawbacks, such as chemoresistance. In this study we combined 5-fluorouracil encapsulated in long-circulating liposomes with simvastatin, also encapsulated in long-circulating liposomes, that was previously proved to exert antitumor actions on the same tumor model. The production of angiogenic/inflammatory proteins was assessed by protein array and the production of markers for tumor aggressiveness (Bcl-2, Bax, and nuclear factor [NF]-κB) were determined by western blot analysis. Intratumor oxidative stress was evaluated through measurement of malondialdehyde level by HPLC, and through spectrophotometric analysis of catalytic activity of catalase and of total antioxidant capacity. Immunohistochemical analysis of tumors for CD31 expression was assessed. Intratumor activity of MMP-2 by gelatin zymography was also carried out. Our results revealed that combined therapies based on liposomal formulations exerted enhanced antitumor activities compared with combined treatment with free drugs. Sequential treatment with liposomal simvastatin and liposomal 5-fluorouracil showed the strongest antitumor activity in C26 colon carcinoma in vivo, mainly through inhibition of tumor angiogenesis. Important markers for cancer progression (Bcl-2, Bax, NF-κB, and intratumor antioxidants) showed that liposomal simvastatin might sensitize C26 cells to liposomal 5-fluorouracil treatment in both regimens tested. The outcome of simultaneous treatment with liposomal formulations was superior to sequential treatment with both liposomal types as the invasive capacity of C26 tumors was strongly increased after the latest treatment. The antitumor efficacy of combined therapy in C26 colon carcinoma might be linked to the restorative effects on proteins balance involved in tumor angiogenesis. K E Y W O R D S 5-fluorouracil, combined therapy, liposomes, resistance, simvastatin | 1345 LUPUT eT aL. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Luput L, Sesarman A, Porfire A, et al. Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5-fluorouracil in vivo.

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“…NDDSs that are modi ed on the surface to express ligands to these receptors could target both tumor blood vessels and tumor cells. Targeting of tumor blood vessels could increase the retention of the NDDSs near the tumor, which eventually increases the distribution in tumor tissues [93]. For example, RGD peptide is a short peptide containing arginine, glycine, and aspartic acid (Arg-Gly-Asp) and is the ligand for integrin αvβ3.…”

Section: Tumor Accumulation and Penetrationmentioning

confidence: 99%

“…In addition, such combinations could downregulate VEGF, MMP2, and MMP9 levels, suggesting they could inhibit tumor metastasis. Sesarman et al [93] developed a long term circulating liposome that could pack CUR and PTX (LCL-CURC-DOX).…”

Section: Immunomodulationmentioning

confidence: 99%

The Application of Nanotechnology in the Codelivery of Active Constituents of Plants and Chemotherapeutics for Overcoming Physiological Barriers during Antitumor Treatment

Xiong

et al. 2019

BioMed Research International

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Antitumor therapy using a combination of drugs has shown increased clinical efficacy. Active constituents derived from plants can offer several advantages, such as high efficiacy, low toxicity, extensive effects, and multiple targets. At present, the combination of plants’ active constituents and chemotherapeutic drugs has attracted increased attention. Nanodrug delivery systems (NDDSs) have been widely used in tumor-targeted therapy because of their efficacy of delivering antitumor drugs. The in vivo process of tumor-targeted NDDSs has several steps. They include blood circulation, tumor accumulation and penetration, target cell internalization and uptake, and drug release and drug response. In each step, NDDSs encounter multiple barriers that prevent their effective delivery to target sites. Studies have been performed to find alternative strategies to overcome these barriers. We reviewed the recent progress of codelivery of active constituents of plants and chemotherapeutics using NDDSs. Progress into transversing the physiological barriers for more effective in vivo antitumor delivery will be discussed in this review.

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Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment

Cited by 63 publications

References 41 publications

Pharmaceutical Development of Liposomes Using the QbD Approach

Pharmaceutical Development of Liposomes Using the QbD Approach

Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5‐fluorouracil in vivo

The Application of Nanotechnology in the Codelivery of Active Constituents of Plants and Chemotherapeutics for Overcoming Physiological Barriers during Antitumor Treatment

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