Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin

Sesărman, Alina; Abrudan, Bianca M.; Tefas, Lucia Ruxandra; Sylvester, Bianca; Licărete, Emilia; Rauca, Valentin Florian; Lupuţ, Lavinia; Pătraș, Laura; Banciu, Manuela; Vlase, Laurian; Porfire, Alina

doi:10.1080/08982104.2019.1682604

Cited by 23 publications

(19 citation statements)

References 55 publications

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“…They are easily scalable, stable, and biocompatible drug delivery systems with a high drug to lipid ratio which also improves the solubility of poorly soluble drugs (Bhatt et al, 2018). It has been shown that solid lipid curcumin nanoparticles enhanced the solubility over native curcumin and reduced that activity of the lipopolysaccharide (LPS)-induced pro-inflammatory mediators NO, PGE 2 , and interleukin (IL)-6 by obstructing the activation of NF-kB (Nahar et al, 2015 Increased the antimalarial and antimelanoma effects, greater encapsulation efficiency, excellent bioactivity, and anticancer activity Basnet et al, 2012;Rogers et al, 2012;Tefas et al, 2017;Sesarman et al, 2018;Chen et al, 2019;Huang et al, 2019;Reddy et al, 2019;Vetha et al, 2019 2 Polymers Polymers are another widely used effective drug delivery system for curcumin. It can able to improve the oral bioavailability and solubility of curcumin.…”

Section: Nanoparticlesmentioning

confidence: 99%

Nanocurcumin: A Promising Candidate for Therapeutic Applications

2020

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Section: Nanoparticlesmentioning

confidence: 99%

Nanocurcumin: A Promising Candidate for Therapeutic Applications

2020

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“…Smart nanomaterials (e.g., pH-sensitive and redox-sensitive nanoparticles) can be applied for targeted delivery of curcumin and DOX, to release their cargo in response to the tumor microenvironment. Besides, the surface of nanoparticles can be modified by receptors and ligands (such as hyaluronic acid and RGD) to promote accumulation in cancer cells (Figure 6) [222][223][224][225][226][227][228][229][230][231][232][233][234]. In Table 3, different nanocarriers applied for codelivery of curcumin and DOX are described.…”

Section: Codelivery Via Biological Nanovehiclesmentioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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“…The encapsulation efficiency values of SIM were 50.72% (LCL-SIM) and 65.21% (IL-13-LCL-SIM), values that indicate potential for technological transfer ( Table 1 ). To assess stability in simulated biological fluids, liposomes were tested in HBBS and in FCS to approximate in vivo fluid conditions ( Sesarman et al, 2021 ). All LCL formulations were diluted with the mentioned fluids in a ratio of 1:100 (v/v) and incubated at 37°C for 24 and 48 h. The size of the liposomes was measured before ( t = 0) and after 24 h ( t = 24) and 48 h ( t = 48 h) incubation, and results are presented in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

et al. 2022

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Primary melanoma aggressiveness is determined by rapid selection and growth of cellular clones resistant to conventional treatments, resulting in metastasis and recurrence. In addition, a reprogrammed tumor-immune microenvironment supports melanoma progression and response to therapy. There is an urgent need to develop selective and specific drug delivery strategies for modulating the interaction between cancer cells and immune cells within the tumor microenvironment. This study proposes a novel combination therapy consisting of sequential administration of simvastatin incorporated in IL-13-functionalized long-circulating liposomes (IL-13-LCL-SIM) and doxorubicin encapsulated into PEG-coated extracellular vesicles (PEG-EV-DOX) to selectively target both tumor-associated macrophages and melanoma cells. To this end, IL-13 was conjugated to LCL-SIM which was obtained via the lipid film hydration method. EVs enriched from melanoma cells were passively loaded with doxorubicin. The cellular uptake of rhodamine-tagged nano-particles and the antiproliferative potential of the treatments by using the ELISA BrdU-colorimetric immunoassay were investigated in vitro. Subsequently, the therapeutic agents were administered i.v in B16.F10 melanoma-bearing mice, and tumor size was monitored during treatment. The molecular mechanisms of antitumor activity were investigated using angiogenic and inflammatory protein arrays and western blot analysis of invasion (HIF-1) and apoptosis markers (Bcl-xL and Bax). Quantification of oxidative stress marker malondialdehyde (MDA) was determined by HPLC. Immunohistochemical staining of angiogenic markers CD31 and VEGF and of pan-macrophage marker F4/80 was performed to validate our findings. The in vitro data showed that IL-13-functionalized LCL were preferentially taken up by tumor-associated macrophages and indicated that sequential administration of IL-13-LCL-SIM and PEG-EV-DOX had the strongest antiproliferative effect on tumor cells co-cultured with tumor-associated macrophages (TAMs). Accordingly, strong inhibition of tumor growth in the group treated with the sequential combination therapy was reported in vivo. Our data suggested that the antitumor action of the combined treatment was exerted through strong inhibition of several pro-angiogenic factors (VEGF, bFGF, and CD31) and oxidative stress-induced upregulation of pro-apoptotic protein Bax. This novel drug delivery strategy based on combined active targeting of both cancer cells and immune cells was able to induce a potent antitumor effect by disruption of the reciprocal interactions between TAMs and melanoma cells.

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Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin

Cited by 23 publications

References 55 publications

Nanocurcumin: A Promising Candidate for Therapeutic Applications

Nanocurcumin: A Promising Candidate for Therapeutic Applications

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

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