Optimization of novel tocopheryl acetate nanoemulsions for parenteral delivery of curcumin for therapeutic intervention of sepsis

Shukla, P.K.; Dwivedi, Pankaj; Gupta, Pramod; Mishra, Prabhat Ranjan

doi:10.1517/17425247.2014.932769

Cited by 35 publications

(33 citation statements)

References 57 publications

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“…Stable NEs enriched with Vitamin E (such as α-, γ- and δ-Tph and T3s) have been successfully developed for parenteral and oral administration, initially as antioxidant therapy [24], as well as a nano-delivery vehicle to enhance the systemic bioavailability of numerous slightly water-soluble anticancer agents, such as paclitaxel [22], etoposide, along with natural polyphenols comparable to CUR, such as quercetin, and Gen [18,24,25]. …”

Section: Resultsmentioning

confidence: 99%

“…Out of these, a nano-emulsification technique has been quite successful, taking advantage of the lipophilic character of CUR, rather than chemical modification or conjugation [6,18]. Owing to their superior pharmaceutical properties (such as good biocompatibility, biodegradability, physical stability, and ease of large-scale production), optimized nanoemulsion (NE) formulations can incorporate hydrophobic CUR as a payload within its VE-based core matrix [10].…”

Section: Introductionmentioning

confidence: 99%

“…Owing to their superior pharmaceutical properties (such as good biocompatibility, biodegradability, physical stability, and ease of large-scale production), optimized nanoemulsion (NE) formulations can incorporate hydrophobic CUR as a payload within its VE-based core matrix [10]. In fact, nano-emulsification of VE compounds has been reported with great success in multiple reports, via the utilization of non-ionic surfactant blends [12,18,19]. Stable NEs enriched with VE compounds (such as γ- and δ-T3s in particular) have been developed for parenteral and oral administration, as nano-delivery vehicles to enhance the systemic bioavailability of many slightly water-soluble chemotherapeutic agents, such as paclitaxel, simvastatin, and Gen [10,20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

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Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas

Steuber

Wadhwa

et al. 2016

IJMS

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Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted δ-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70:30 wt % surfactant mix of Lutrol F-127:VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-potential = −35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-T3 NE produced superior cytotoxicity profiles, in concentration- and time-dependent manners (p ≤ 0.05), at least three to four folds lower IC50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas

Steuber

Wadhwa

et al. 2016

IJMS

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“…indicating that it is a suitable treatment approach for inflammatory bowel disease (IBD). Shukla et al (92) proved that nanoemulsion of curcumin in rats exhibited LPS-induced lung-and liver-associated injury due to minimizing neutrophil migration, reducing TNF-α levels, and oxidative stress. Exosome-mediated curcumin delivery can be efficient to activate myeloid cells in vivo (in a lipopolysaccharide (LPS)induced septic shock mouse model) (93).…”

Section: Inflammatory Diseasesmentioning

confidence: 99%

Therapeutic Applications of Curcumin Nanoformulations

Yallapu

Nagesh

Jaggi

et al. 2015

AAPS J

290

177

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Abstract. Curcumin (diferuloylmethane) is a bioactive and major phenolic component of turmeric derived from the rhizomes of curcuma longa linn. For centuries, curcumin has exhibited excellent therapeutic benefits in various diseases. Owing to its anti-oxidant and anti-inflammatory properties, curcumin plays a significant beneficial and pleiotropic regulatory role in various pathological conditions including cancer, cardiovascular disease, Alzheimer's disease, inflammatory disorders, neurological disorders, and so on. Despite such phenomenal advances in medicinal applications, the clinical implication of native curcumin is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics. However, these issues can be overcome by utilizing an efficient delivery system. Active scientific research was initiated in 2005 to improve curcumin's pharmacokinetics, systemic bioavailability, and biological activity by encapsulating or by loading curcumin into nanoform(s) (nanoformulations). A significant number of nanoformulations exist that can be translated toward medicinal use upon successful completion of pre-clinical and human clinical trials. Considering this perspective, current review provides an overview of an efficient curcumin nanoformulation for a targeted therapeutic option for various human diseases. In this review article, we discuss the clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine. In addition, this review presents a concise summary of the actions required to develop curcumin nanoformulations as pharmaceutical or nutraceutical candidates.

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“…At low concentrations, VEA was not cytotoxic. Moreover, VEA has been employed as a carrier in therapeutic interventions [61], suggesting that it may act as a carrier for THC in the blood and the brain. Upon aerosolization, VEA or its formed oxidant derivatives may interact with phospholipids and surfactants of the epithelial lining fluid, thus adversely affect the normal lung function [62,63].…”

Section: Resultsmentioning

confidence: 99%

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

Muthumalage

Lucas

Wang

et al. 2020

Preprint

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Recently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT) may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges, and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined at SARS-COV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated pro-inflammatory markers in the pathogenesis of EVALI.

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Optimization of novel tocopheryl acetate nanoemulsions for parenteral delivery of curcumin for therapeutic intervention of sepsis

Abstract: The findings suggest that the therapeutic performance (i.e., reduction in oxidative damage in tissues) of CUR can be enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics and tissue distribution) as a platform for drug delivery in sepsis-induced organ injury.

Cited by 35 publications

References 57 publications

Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas

Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas

Therapeutic Applications of Curcumin Nanoformulations

Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins

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