Resveratrol-loaded nanocarriers: Formulation, optimization, characterization and in vitro toxicity on cochlear cells

Musazzi, Umberto M.; Youm, Ibrahima; Murowchick, James B.; Ezoulin, Miezan J.; Youan, Bi‐Botti C.

doi:10.1016/j.colsurfb.2014.03.054

Cited by 32 publications

(20 citation statements)

References 34 publications

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“…23 Different NPs based on silica (unloaded NPs), polyethylene glycol (PEG) loaded with resveratrol or copolymers like poly-ε-caprolactone-PEG (PCL-PEG) loaded with furosemide were tested in vitro showing good internalization by auditory cells. [24][25][26] Different types of nanocarriers have been used in vivo to ameliorate sensorineural hearing loss. Lipid NPs showed a high capacity to incorporate hydrophobic or hydrophilic drugs, and improve stability of encapsulated drugs.…”

Section: Introductionmentioning

confidence: 99%

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Martín-Saldaña¹,

Palao-Suay

Trinidad³

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: Nanomedicine: Nanotechnology, Biology and Medicine 12.4 (2016) Abstract 6α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was found.Background Cisplatin (CDDP) is a highly effective chemotherapeutic agent against a variety of solid tumors including head and neck, lungs, ovary, bladder and testicles; however, it presents severe side-effects. Marullo et al1 described a double way of CDDP-induced cytotoxicity: CDDP binding to guanine bases on nuclear DNA and the formation of inter-and intra-strand chain crosslinking trigger cell apoptosis because of replication and transcription blockage; CDDP also has a direct effect on mitochondrial DNA resulting in the impairment of electron 32 transport chain protein synthesis leading to ROS generation. Increasing doses incorporated into protocols, with the aim of increasing cure rates, are related with serious adverse effects that affect kidney function, nervous system and hearing. CDDP induces apoptosis of inner ear cell by binding to DNA, reactive oxygen species (ROS) generation, increased lipid peroxidation and Ca 2+ influx, and inflammation events.2 Hearing impairment begins in the high frequencies and progresses to midrange when patient receives doses higher than 100 mg/m 2. Patients who receive ultrahigh doses of CDDP (150-225 mg/m 42 2), show hearing loss in the high and extended high frequencies in 100% of cases. 44 3 There is substantial variability in susceptibility to the ototoxic effects of CDDP. Rapid intravenous bolus injections, high cumulative doses, pre-existing hearing loss, renal insufficiency, anemia, hypoalbuminemia, and prior cranial irradiation are some of the factors that can play a role in CCDP toxicity. The incidence and severity of hearing loss

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Section: Introductionmentioning

confidence: 99%

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Martín-Saldaña¹,

Palao-Suay

Trinidad³

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Besides, resveratrol-loaded lipid-core nanocapsules have higher antioxidant and anti-inflammatory activities compared to the resveratrol alone [37]. Overall, polymeric nanoparticles [38,39], solid lipid nanoparticles [40,41], self-emulsifying drug delivery systems [42,43], nanoemulsions [44,45], liposomes [46,47], nanosuspensions [48] and nanofibers [49] have been developed for delivery of resveratrol and the results have been satisfactory.…”

Section: Resveratrolmentioning

confidence: 99%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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“…PLGA and poly (ε-caprolactone)-poly (ethylene glycol) (PCL-PEG) di-block were used to obtain reservatrol NPs [79]. PLGA was selected for its well-known safety profile and its ability to control drug release, while PCL-PEG di-block was used on one hand to stabilize the NPs surface and on the other hand to improve its drug loading.…”

Section: Phytosomesmentioning

confidence: 99%

Modern drug delivery strategies applied to natural active compounds

Puglia

Lauro

Tirendi

et al. 2016

Expert Opinion on Drug Delivery

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Colloidal drug delivery systems (CDDSs) are innovative carriers that have been studied in pharmaceutical field from many years to overcome unfavorable physical and chemical features of synthetic drugs. Recently the use of CDDS as carriers for phytochemicals has seen an exponential increase which, in some cases, has led to the rediscovery of ancient and forgotten natural molecules. Area covered: This article focuses on the main features of CDDS, particularly micro- and nanoemulsions, vesicular carriers and micro- and nanoparticles, loaded with natural active compounds. A detailed review of the literature is presented, introducing the importance of these systems in terms of their capability to optimize the stability of phytochemicals, their absorption through biological membranes and their bioavailability. Expert opinion: The delivery of phytochemicals is problematic due to poor solubility, poor permeability, low bioavailability, instability in biological milieu and extensive first-pass metabolism. Global research efforts investigating nanotechnology have attempted to overcome these limitations rediscovering and, in some cases, 'discovering ex novo' unexpected virtues and benefits associated to these compounds. The 'nanotechnological approach' can definitely enhance the pharmacokinetics and therapeutic index of natural active compounds and improve their performance in therapy.

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Resveratrol-loaded nanocarriers: Formulation, optimization, characterization and in vitro toxicity on cochlear cells

Cited by 32 publications

References 34 publications

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

Modern drug delivery strategies applied to natural active compounds

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