Recent Advances in the Application of Vitamin E TPGS for Drug Delivery.
TL;DR: The recent advances of TPGS in drug delivery including T PGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGs based formulations are discussed, focused on enhancing delivery efficiency as well as the therapeutic effect of agents.
Abstract: D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.
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TL;DR: Recent progress on strategies to address PLA problems is summarized, including novel fabrication techniques, high-performance PLA composites, and their applications for tissue engineering and drug delivery.
Abstract: Biodegradable poly(lactic acid) (PLA) presents suitable physicochemical properties and biocompatibility for biomedical engineering. However, PLA has some drawbacks, such as low cell adhesion, biological inertness, low degradation rate, and acid degradation by-products. In this review, recent progress on strategies to address these problems is summarized, including novel fabrication techniques, high-performance PLA composites, and their applications for tissue engineering and drug delivery. The scaffolds, especially for bone regeneration, blood vessels, organs, and skin regeneration are evaluated, in terms of in vivo and in vitro biocompatibility and biodegradability. The enhanced mechanical, thermal, and rheological properties of PLA biocomposites are analyzed in detail. PLA biocomposites for drug encapsulation, sustained release, and tumor-targeting are also reviewed. Furthermore, the challenges and future perspectives on PLA-based biocomposites are discussed.
206 citations
TL;DR: An energy depletion-based anticancer strategy by selectively activating excessive mitophagy in cancer cells by fabricating a type of mitochondria-targeting nanomicelles via the self-assembly of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and dc-IR825 (a near-infrared cyanine dye and a photothermal agent).
68 citations
TL;DR: It is suggested that complementary interactions among PTT/PDT/CT modalities can enhance the efficiency of the combined therapy for MDR tumor.
Abstract: Currently, the simple integration of multiple therapeutic agents within a single nanostructure for combating multidrug resistance (MDR) tumors yet remains a challenge Herein, we report a photoresponsive nanocluster (NC) system prepared by installing polydopamine (PDA) nanoparticle clusters on the surface of d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) (a drug efflux inhibitor) micelles solubilized with IR780 (a photosensitizer) to achieve a combined chemotherapy (CT)/photothermal therapy (PTT)/photodynamic therapy (PDT) for drug-resistant breast cancer Mediated by the fluorescence resonance energy transfer and radical scavenging properties of PDA, NC shows prominently quenched fluorescence emission (∼78%) and inhibited singlet oxygen generation (∼67%) upon exposure to near-infrared (NIR) light (808 nm, 05 W cm-2), favoring a highly efficient PTT module Meanwhile, the photothermal heat can also boost the release of doxorubicin hydrochloride whose intracellular accumulation can be greatly enhanced by TPGS Interestingly, the first NIR irradiation and subsequent incubation (∼24 h) can induce the gradual relocation and disintegration of PDA nanoparticles, thereby leading to activated PDT therapy under the second irradiation Upon the temporally controlled sequential application of PTT/PDT, the developed NC exhibited a great potential to treat MDR cancer both in vitro and in vivo These findings suggest that complementary interactions among PTT/PDT/CT modalities can enhance the efficiency of the combined therapy for MDR tumor
66 citations
TL;DR: This work proposes the encapsulation of sucupira essential oil in nanostructured lipid carriers (NLCs), a second generation of lipid nanoparticles which act as new controlled drug delivery system (DDS) for diabetes mellitus.
Abstract: Essential oils are odorant liquid oily products consisting of a complex mixture of volatile compounds obtained from a plant raw material. They have been increasingly proven to act as potential natural agents in the treatment of several human conditions, including diabetes mellitus (DM). DM is a metabolic disorder characterized by chronic hyperglycemia closely related to carbohydrate, protein and fat metabolism disturbances. In order to explore novel approaches for the management of DM our group proposes the encapsulation of sucupira essential oil, obtained from the fruits of the Brazilian plants of the genus Pterodon, in nanostructured lipid carriers (NLCs), a second generation of lipid nanoparticles which act as new controlled drug delivery system (DDS). Encapsulation was performed by hot high-pressure homogenization (HPH) technique and the samples were then analyzed by dynamic light scattering (DLS) for mean average size and polydispersity index (PI) and by electrophoretic light scattering (ELS) for zeta potential (ZP), immediately after production and after 24 h of storage at 4 °C. An optimal sucupira-loaded NLC was found to consist of 0.5% (m/V) sucupira oil, 4.5% (m/V) of Kollivax® GMS II and 1.425% (m/V) of TPGS (formulation no. 6) characterized by a mean particle size ranging from 148.1 ± 0.9815 nm (0 h) to 159.3 ± 9.539 nm (at 24 h), a PI from 0.274 ± 0.029 (0 h) to 0.305 ± 0.028 (24 h) and a ZP from -0.00236 ± 0.147 mV (at 0 h) to 0.125 ± 0.162 (at 24 h). The encapsulation efficiency and loading capacity were 99.98% and 9.6%, respectively. The optimized formulation followed a modified release profile fitting the first order kinetics, over a period of 8 h. In vitro cytotoxicity studies were performed against Caco-2 cell lines, for which the cell viability above 90% confirmed the non-cytotoxic profile of both blank and sucupira oil-loaded NLC.
55 citations
Cites background from "Recent Advances in the Application ..."
...The selected surfactant d-α-tocopheryl polyethylene glycol succinate, or vitamin E TPGS, has been approved by the Food and Drug Administration as a safe ingredient and is commonly used in pharmaceutical dosage forms [71]....
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...The selected surfactant D-α-tocopheryl polyethylene glycol succinate, or vitamin E TPGS, has been approved by the Food and Drug Administration as a safe ingredient and is commonly used in pharmaceutical dosage forms [71]....
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TL;DR: The introduction of US-targeted microbubble destruction technology was proven to render the complexes with enhanced intracellular uptake and anticancer efficacy in vitro and improved chemotherapeutic efficacy and fluorescence imaging of tumors in vivo due to the produced sonoporation effect.
55 citations
Cites background from "Recent Advances in the Application ..."
...As a P-gp inhibitor, TPGS can bind to mitochondria and induce decreased membrane potential, thus reducing the level of intracellular ATP, increasing ROS levels and activating cell apoptosis to overcome MDR [12]....
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...Furthermore, TPGS, as a mitochondriotropic substance, was reported to have mitochondrial targeting capability [11], which may accelerate the mitochondrial dysfunction [12]....
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References
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TL;DR: The concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers, including breast and ovarian cancer, is supported.
Abstract: Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.
6,938 citations
"Recent Advances in the Application ..." refers background in this paper
...In addition, TPGS is a powerful anticancer agent when dealing with breast cancer with high level of human epidermal growth factor receptor 2 (HER2) expression [61]....
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TL;DR: The ability to predict and circumvent drug resistance is likely to improve chemotherapy, and it has become apparent that resistance exists against every effective drug, even the authors' newest agents.
Abstract: Chemotherapeutics are the most effective treatment for metastatic tumours. However, the ability of cancer cells to become simultaneously resistant to different drugs--a trait known as multidrug resistance--remains a significant impediment to successful chemotherapy. Three decades of multidrug-resistance research have identified a myriad of ways in which cancer cells can elude chemotherapy, and it has become apparent that resistance exists against every effective drug, even our newest agents. Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy.
5,105 citations
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...What’s worse, decades of research has identified that this phenomenon exists in nearly every effective drug, even the newest therapeutic agents [9]....
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TL;DR: How different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule is reviewed.
Abstract: Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.
4,149 citations
TL;DR: This review focuses on recently discovered cellular pathways that are activated in response to cisplatin, including those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death.
Abstract: Cisplatin, carboplatin and oxaliplatin are platinum-based drugs that are widely used in cancer chemotherapy. Platinum–DNA adducts, which are formed following uptake of the drug into the nucleus of cells, activate several cellular processes that mediate the cytotoxicity of these platinum drugs. This review focuses on recently discovered cellular pathways that are activated in response to cisplatin, including those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death. Such knowledge of the cellular processing of cisplatin adducts with DNA provides valuable clues for the rational design of more efficient platinum-based drugs as well as the development of new therapeutic strategies.
3,254 citations
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...However, the clinical application is limited for low solubility, nephrotoxicity, severe peripheral neurotoxicity, inherent and acquired drug resistance [59]....
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TL;DR: Results are consistent with a function for P-glycoprotein as an energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
1,914 citations