Design, Synthesis, and Biological Evaluation of Dexamethasone–Salvianolic Acid B Conjugates and Nanodrug Delivery against Cisplatin-Induced Hearing Loss

Ye, Ruiqin; Sun, Lifang; Peng, Jinghui; Wu, Aixin; Chen, Xiaozhu; Wen, Li; Bai, Chujie; Chen, Gang

doi:10.1021/acs.jmedchem.0c01916

Cited by 11 publications

(11 citation statements)

References 63 publications

(109 reference statements)

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“…The guinea pig HL model was established via an intraperitoneal injection of 12 mg/kg CDDP. 32 As shown in Figure 5B−E, the survival rates of OHCs in the basal turns in CUR-, CUR-PLGA NP-, and CUR-CS/PLGA NP-treated groups were dramatically increased, compared to the CDDP group at a dose of 4 μg/kg (P ≤ 0.001). However, Dex protected guinea pig hair cells at an effective dose of 2000 μg/kg but not 4 μg/kg.…”

Section: Resultsmentioning

confidence: 74%

“…37 Typically, drug delivery using NPs has tremendous benefits owing to prolonged circulation, enhanced drug aqueous solubility, bioavailability, and the ability to overcome physiological barriers. 32,38 In the present study, CUR-NPs were made by utilizing the single emulsion-solvent evaporation technique, and the morphology, particle sizes, and zeta potentials were evaluated. According to the observed results, CUR-NPs had narrow distributions of particle size of around 180 nm.…”

Section: Discussionmentioning

confidence: 87%

“…Guinea pigs were given different formulations at 1 and 24 h before CDDP injection (Figure A). The guinea pig HL model was established via an intraperitoneal injection of 12 mg/kg CDDP . As shown in Figure B–E, the survival rates of OHCs in the basal turns in CUR-, CUR-PLGA NP-, and CUR-CS/PLGA NP-treated groups were dramatically increased, compared to the CDDP group at a dose of 4 μg/kg ( P ≤ 0.001).…”

Section: Resultsmentioning

confidence: 96%

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Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss

et al. 2022

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Overexpression of apoptotic factors in the inner ear is generally proven to induce ototoxicity. This has aroused research interest in various antiapoptotic drugs, the most representative of which is curcumin (CUR). In this study, two nanoformulations of CUR were developed with sustained-release behavior to improve their protective effects against ototoxic hearing loss (HL), which were the nanoparticles of CUR-loaded poly(lactic acid–glycolic acid) (CUR-PLGA NPs) and CUR-loaded chitosan-coated PLGA NPs (CUR-CS/PLGA NPs). The obtained results revealed that both CUR-NPs provided otoprotection in vitro and in vivo, and their effective doses in guinea pigs were much less than that of dexamethasone, which was clinically used to treat HL. Moreover, relative to CUR and CUR-PLGA NPs, CUR-CS/PLGA NPs exhibited the highest accumulation in HEI-OC1 cells and guinea pigs’ cochlea. In pharmacodynamic experiments, the optimal administration timing was investigated, and CUR-CS/PLGA NPs showed sustained efficacy and the best hearing improvement at all tested sound frequencies. Lastly, the protective effect of CUR nanoformulations was further validated via inhibition of Caspase-3 and Bax activation, thereby reducing the concentration of reactive oxygen species and protecting mitochondrial integrity in hair cells. Collectively, CUR-CS/PLGA NPs demonstrated potent and lasting effects against ototoxic HL, making our novel formulation a promising candidate for the alleviation of sensorineural HL.

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Section: Resultsmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 96%

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Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss

et al. 2022

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“…Ye et al ( 34 ) conjugated DEX (hydrophobic) to a hydrophilic drug (SAL) via an ester bond to form a nanomolecule that was used for otoprotection. SAL has been widely used to treat cardiovascular and cerebrovascular diseases.…”

Section: Previous Studiesmentioning

confidence: 99%

The Use of Nanoparticles in Otoprotection

Barbara

Covelli²,

Filippi³

et al. 2022

Front. Neurol.

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The inner ear can be insulted by various noxious stimuli, including drugs (cisplatin and aminoglycosides) and over-acoustic stimulation. These stimuli damage the hair cells giving rise to progressive hearing loss. Systemic drugs have attempted protection from ototoxicity. Most of these drugs poorly reach the inner ear with consequent ineffective action on hearing. The reason for these failures resides in the poor inner ear blood supply, the presence of the blood-labyrinthine barrier, and the low permeability of the round window membrane (RWM). This article presents a review of the use of nanoparticles (NPs) in otoprotection. NPs were recently used in many fields of medicine because of their ability to deliver drugs to the target organs or cells. The studies included in the review regarded the biocompatibility of the used NPs by in vitro and in vivo experiments. In most studies, NPs proved safe without a significant decrease in cell viability or signs of ototoxicity. Many nano-techniques were used to improve the drugs' kinetics and efficiency. These techniques included encapsulation, polymerization, surface functionalization, and enhanced drug release. In such a way, it improved drug transmission through the RWM with increased and prolonged intra-cochlear drug concentrations. In all studies, the fabricated drug-NPs effectively preserved the hair cells and the functioning hearing from exposure to different ototoxic stimuli, simulating the actual clinical circumstances. Most of these studies regarded cisplatin ototoxicity due to the wide use of this drug in clinical oncology. Dexamethasone (DEX) and antioxidants represent the most used drugs in most studies. These drugs effectively prevented apoptosis and reactive oxygen species (ROS) production caused by ototoxic stimuli. These various successful experiments confirmed the biocompatibility of different NPs and made it successfully to human clinical trials.

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“…Moreover, conjugates NPs predominantly have improved hair cell damage in HEI-OC1 cells and hair cells of zebrafish and reversed hearing loss in cisplatin pretreated guinea pig model by triggering the glucocorticoid receptor. 126 Glucocorticoid receptor pathway may be major mechanisms for otoprotective effects of DEX in DEX-SAL conjugates NPs and PEG-PLA-DEX-NPs. 102…”

Section: Cisplatin-induced Hearing Loss (Cihl)mentioning

confidence: 99%

An Overview of Nanoparticle Drug Delivery for Ototoxin and Noise Mediated Hearing Loss Treatment

Sreeharsha¹,

Nataraj²,

Jang³

et al. 2022

Ind. J. Pharm. Edu. Res

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Efficient delivery of therapeutic material to target site of the inner ear is considered as the most challenging process due to their poor blood flow and inaccessibility sensitivity towards chemical stimuli, inability of drug to be delivered as well. Novel nanoparticlebased drug transport approaches have emerged for overcoming the restriction associated with inner ear therapeutic material delivery. The main focus of this article is to highlight the potential benefits, pre-clinical level otoprotective effect of different types of NPs based payload delivery strategies in mitigating sensorineural hearing impairment resulting from medication (cisplatin and antibiotic treatment) and noise exposure. This review converses about advantage of nanocarrier assisted targeted cell specific inner ear drug delivery approach and demonstrates that targeted NPs delivery systems have the capability to be utilized as vehicle to transport therapeutic materials into the OHCs within the cochlea in controlled and sustained way and maximize following therapeutic effects. Efficacy of systemic and minimally invasive intratympanic and RWM approach for delivering steroids/ genetic material to the inner ear has also been compared in this article. Understanding the importance (design, formulation, cochlear biocompatibility and cell specific binding efficiency of NPs, mechanistic pathways, route of delivery, positive therapeutic outcomes) and hitches (adverse effects after treatment, negative therapeutic outcome) of currently available NPs based drug delivery systems offer new opportunity to develop best treatment methods for sensorineural hearing dysfunction.

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Design, Synthesis, and Biological Evaluation of Dexamethasone–Salvianolic Acid B Conjugates and Nanodrug Delivery against Cisplatin-Induced Hearing Loss

Cited by 11 publications

References 63 publications

Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss

Curcumin-Encapsulated Chitosan-Coated Nanoformulation as an Improved Otoprotective Strategy for Ototoxic Hearing Loss

The Use of Nanoparticles in Otoprotection

An Overview of Nanoparticle Drug Delivery for Ototoxin and Noise Mediated Hearing Loss Treatment

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