Solid lipid nanoparticles co-loaded with doxorubicin and α-tocopherol succinate are effective against drug-resistant cancer cells in monolayer and 3-D spheroid cancer cell models

Oliveira, Mariana Silva; Aryasomayajula, Bhawani; Pattni, Bhushan S.; Mussi, Samuel Vidal; Ferreira, Lucas Antônio Miranda; Торчилин, В. П.

doi:10.1016/j.ijpharm.2016.08.049

Cited by 71 publications

(77 citation statements)

References 32 publications

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“…94 In this regard, MCTS from MDR cell lines such as breast cancer MCF7/ Adr or ovarian cancer NCI-ADR-RES are useful tools to evaluate innovative solutions to restore DOX cytotoxicity as was shown with intrinsic drug-resistant glioblastoma U87MG cells. 70,71,[95][96][97][98] DOX-loaded nanoplatforms (targeted or nontargeted) that allow the simultaneous administration of several anticancer agents were evaluated in MCTS based on three criteria: accumulation, penetration and cytotoxic effects (Table 2). 70,71,[95][96][97][98] An excellent example of what can be done was the coloading of DOX with the MDR modulator curcumin (CUR) that inhibits different resistance-related pathways.…”

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confidence: 99%

“…70,71,[95][96][97][98] DOX-loaded nanoplatforms (targeted or nontargeted) that allow the simultaneous administration of several anticancer agents were evaluated in MCTS based on three criteria: accumulation, penetration and cytotoxic effects (Table 2). 70,71,[95][96][97][98] An excellent example of what can be done was the coloading of DOX with the MDR modulator curcumin (CUR) that inhibits different resistance-related pathways. 94,98 Polymeric micelles loaded with DOX and/or CUR (zeta potential of -4.4 mV, 15 nm in size) were decorated with a single-chain fragment variable (scFv), smaller, more stable and less immunogenic than IgG antibody, and were addressed against the GLUT1 protein in overexpressed glioblastoma cells.…”

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confidence: 99%

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Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

112

107

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The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS) model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM) components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs) play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a better comprehension of the interactions between NPs and tumor components that affect tumor drug delivery. MCTS is particularly suitable for the high-throughput screening of new nanodrugs.

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confidence: 99%

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confidence: 99%

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Millard¹,

Yakavets²,

Zorin³

et al. 2017

IJN

112

107

View full text Add to dashboard Cite

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“…The combination of TS – an analogue of vitamin E – and DOX loaded into a lipid nanoparticle demonstrated promising in vitro results [16] with modest potential for off target toxicity, therefore forming the foundation of these studies. We developed a novel drug delivery system with in vivo properties that show favorable pharmacodynamics and antitumor activity.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, our research group demonstrated that TS improves encapsulation of DOX into lipid nanoparticles [15], with increased cytotoxicity in monolayer and 3-D spheroid models, against MCF-7/Adr and NCI/Adr line cells [16]. Therefore, the aim of this work was to evaluate the in vivo properties of this NLC formulation in an experimental model.…”

Section: Introductionmentioning

confidence: 99%

α- Tocopherol succinate loaded nano-structed lipid carriers improves antitumor activity of doxorubicin in breast cancer models in vivo

Fernandes

Silva

Seabra

et al. 2018

Biomedicine & Pharmacotherapy

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Combination-based chemotherapies have been the standard treatment for multiple solid tumors since the 1960s. Combined therapies where both agents have toxicity results in dose-limiting effects. α- tocopherol succinate (TS) is an analogue of vitamin E that exhibits antitumor properties in the absence of toxicity. Hence, its combination with a frontline chemotherapy, doxorubicin (DOX) is an alternative to increase antitumor efficacy. Therefore, the aim of this work was to evaluate the antitumor activity of nanostructed lipid carriers (NLC) loaded with TS and DOX. The NLC-TS-DOX were prepared, characterized and radiolabeled with technetium-99m. Cytotoxicity studies were performed in vitro, using two breast cancer cell lines, MDA-MB-231 and 4T1. Biodistribution and antitumor activity were evaluated in 4T1 tumor-bearing mice. The results showed that NLC-TS-DOX had a small diameter (85 nm) and a long blood clearance (Tβ = 1107.71 min) that consequently resulted in a higher tumor uptake compared to contralateral muscle for up to 48 h. Drug combination studies in MDA-MB-231 and 4T1 cells showed a combination index below 0.8 at ED for both cell lines. Interestingly, a high synergism was found at ED Antitumor activity showed a better control of tumor growth for animals treated with NLC-ST-DOX. The small particle size, along with the EPR effect and the controlled release of DOX from the particle, associated with the synergic combination between TS and DOX led to an increase of the antitumor efficacy. Therefore, NLC-TS-DOX can be considered a plausible alternative to improve antitumor efficacy in DOX therapeutic regimens.

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“…In general, lipid nanoparticles have advantages over other systems used for topical administration: more compatibility with the skin, as lipids are normal components of its structures , enhanced penetration of active compounds in the stratum corneum , low cost, and simple and easy‐to‐scale preparation , excellent physical stability, with no leakage of encapsulated active substances , chemical versatility and biodegradability , controllable release profiles , protection of the encapsulated substance against degradation processes induced by the external medium . …”

Section: Introductionmentioning

confidence: 99%

Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review

Sáez

Souza

Mansur

2018

Intern J of Cosmetic Sci

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The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E.

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Solid lipid nanoparticles co-loaded with doxorubicin and α-tocopherol succinate are effective against drug-resistant cancer cells in monolayer and 3-D spheroid cancer cell models

Cited by 71 publications

References 32 publications

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

α- Tocopherol succinate loaded nano-structed lipid carriers improves antitumor activity of doxorubicin in breast cancer models in vivo

Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review

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