pH-sensitive polymeric nanoparticles with antioxidant and anti-inflammatory properties against cisplatin-induced hearing loss

Martín-Saldaña, Sergio; Palao-Suay, Raquel; Aguilar, María Rosa; García‐Fernández, Luis; Arévalo, Humberto; Trinidad, Almudena; Ramírez‐Camacho, Rafael; Román, Julio San

doi:10.1016/j.jconrel.2017.11.032

Cited by 37 publications

(22 citation statements)

References 56 publications

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“…Here we have used glucocorticoids commonly used as co-therapies in anti-cancer treatments with cisplatin to reduce hearing loss without altering its antimitogenic potential. Here we report that SLN loaded with either dexamethasone or hydrocortisone were efficiently up-taken by auditory cells (2–24 h) and that the glucocorticoid effective dose lowered with respect to those previously reported by using other nanocarriers [17,18,27,44,55,58]. Notably, SLNs were not cytotoxic and no differences in cell viability were observed in the range tested, 50–750 µg/mL.…”

Section: Discussionsupporting

confidence: 50%

“…In this context, drug delivery formulations based on hydrogels and nanoparticles have been explored [11,12,13]. Nanoparticles of different chemical natures have been tested for their potential to cross the round window membrane and their capacity to biodegrade [14], including synthetic, amphiphilic, polymeric nanoparticles covalently linked to drugs or interfering RNAs [15,16,17,18]. Lipid nanoparticles are biodegradable and can deliver both hydrophilic and lipophilic drugs depending on their geometry and composition [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Cervantes

Arana

Murillo-Cuesta

et al. 2019

JCM

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Cisplatin is a chemotherapeutic agent that causes the irreversible death of auditory sensory cells, leading to hearing loss. Local administration of cytoprotective drugs is a potentially better option co-therapy for cisplatin, but there are strong limitations due to the difficulty of accessing the inner ear. The use of nanocarriers for the efficient delivery of drugs to auditory cells is a novel approach for this problem. Solid lipid nanoparticles (SLNs) are biodegradable and biocompatible nanocarriers with low solubility in aqueous media. We show here that stearic acid-based SLNs have the adequate particle size, polydispersity index and ζ-potential, to be considered optimal nanocarriers for drug delivery. Stearic acid-based SLNs were loaded with the fluorescent probe rhodamine to show that they are efficiently incorporated by auditory HEI-OC1 (House Ear Institute-Organ of Corti 1) cells. SLNs were not ototoxic over a wide dose range. Glucocorticoids are used to decrease cisplatin-induced ototoxicity. Therefore, to test SLNs’ drug delivery efficiency, dexamethasone and hydrocortisone were tested either alone or loaded into SLNs and tested in a cisplatin-induced ototoxicity in vitro assay. Our results indicate that the encapsulation in SLNs increases the protective effect of low doses of hydrocortisone and lengthens the survival of HEI-OC1 cells treated with cisplatin.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Cervantes

Arana

Murillo-Cuesta

et al. 2019

JCM

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“…Polymeric NPs based on smart synthetic amphiphilic copolymers were used to transport and release in a controlled way dexamethasone in the inner ear to protect against the ototoxic effect of cisplatin [94]. Polymers based on the methacrylic derivatives of ibuprofen, α-tocopherol, and α-tocopheryl succinate were connected by free polymerization to vinylimidazole and vinylpyrrolidone, and then precipitated to obtain the pH-responsive NPs.…”

Section: Polymeric Formulationsmentioning

confidence: 99%

Recent Developments in the Reduction of Oxidative Stress through Antioxidant Polymeric Formulations

et al. 2019

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Reactive oxygen and nitrogen species (RONS) are produced endogenously in our body, or introduced through external factors, such as pollution, cigarette smoke, and excessive sunlight exposure. In normal conditions, there is a physiological balance between pro-oxidant species and antioxidant molecules that are able to counteract the detrimental effect of the former. Nevertheless, when this homeostasis is disrupted, the resulting oxidative stress can lead to several pathological conditions, from inflammation to cancer and neurodegenerative diseases. In this review, we report on the recent developments of different polymeric formulations that are able to reduce the oxidative stress, from natural extracts, to films and hydrogels, and finally to nanoparticles (NPs).

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“…The former ones occur inherently and are beneficial for clinical application. A designed pH-sensitive polymeric nanoparticle system, triggered by an acid environment due to increased ROS and inflammation, can release encapsulated dexamethasone and ameliorate hearing loss by intratympanic administration (Martin-Saldana et al, 2018). Endogenous stimuli are favored by systemic administration and only activated for regulated release at specific sites (Movahedi et al, 2015).…”

Section: Environmental Stimuli Systemsmentioning

confidence: 99%

Current Strategies to Combat Cisplatin-Induced Ototoxicity

Chen

et al. 2020

Front. Pharmacol.

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Cisplatin is widely used for the treatment of a number of solid malignant tumors. However, ototoxicity induced by cisplatin is an obstacle to effective treatment of tumors. The basis for this toxicity has not been fully elucidated. It is generally accepted that hearing loss is due to excessive production of reactive oxygen species by cells of the cochlea. In addition, recent data suggest that inflammation may trigger inner ear cell death through endoplasmic reticulum stress, autophagy, and necroptosis, which induce apoptosis. Strategies have been extensively explored by which to prevent, alleviate, and treat cisplatin-induced ototoxicity, which minimize interference with antitumor activity. Of these strategies, none have been approved by the Federal Drug Administration, although several preclinical studies have been promising. This review highlights recent strategies that reduce cisplatin-induced ototoxicity. The focus of this review is to identify candidate agents as novel molecular targets, drug administration routes, delivery systems, and dosage schedules. Animal models of cisplatin ototoxicity are described that have been used to evaluate drug efficacy and side effect prevention. Finally, clinical reports of otoprotection in patients treated with cisplatin are highlighted. For the future, high-quality studies are required to provide reliable data regarding the safety and effectiveness of pharmacological interventions that reduce cisplatin-induced ototoxicity.

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pH-sensitive polymeric nanoparticles with antioxidant and anti-inflammatory properties against cisplatin-induced hearing loss

Cited by 37 publications

References 56 publications

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Recent Developments in the Reduction of Oxidative Stress through Antioxidant Polymeric Formulations

Current Strategies to Combat Cisplatin-Induced Ototoxicity

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