The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

Yoon, Ji Young; Yang, Keum‐Jin; Park, Shi-Nae; Kim, Dong-Kee; Kim, Jong-Duk

doi:10.2147/ijn.s114241

Cited by 28 publications

(18 citation statements)

References 31 publications

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“… 2016 ; Yoon et al. 2016 ; Malaekeh-Nikouei et al 2018 ). Moreover, with high affinity to its intracellular receptor, Dexa attaches to its cytoplasmic receptor resulting in the transportation of this complex and whatever conjugated to Dexa to the nucleus (Ma et al.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

Malaekeh‐Nikouei

Rezaee

Gholami

et al. 2018

Pharmaceutical Biology

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Context: Polypropylenimine (PPI), a cationic dendrimer with defined structure and positive surface charge, is a potent non-viral vector. Dexamethasone (Dexa) conveys to the nucleus through interaction with its intracellular receptor. Objective: This study develops efficient and non-toxic gene carriers through conjugation of Dexa at various percentages (5, 10 and 20%) to the fourth and the fifth generation PPIs (PPIG4s and PPIG5s). Materials and methods: The 21-OH group of Dexa (0.536 mmol) was modified with methanesulfonyl chloride (0.644 mmol) to activate it (Dexa-mesylate), and then it was conjugated to PPIs using Traut's reagent. After dialysis (48 h) and lyophilization, the physicochemical characteristics of products (PPI-Dexa) including zeta potential, size, buffering capacity and DNA condensing capability were investigated and compared with unmodified PPIs. Moreover, the cytotoxicity and transfection activity of the Dexa-modified PPIs were assessed using Neuro2A cells. Results: Transfection of PPIG4 was close to PEI 25 kDa. Although the addition of Dexa to PPIG4s did not improve their transfection, their cytotoxicity was improved; especially in the carrier to DNA weight ratios (C/P) of one and two. The Dexa conjugation to PPIG5s enhanced their transfection at C/P ratio of one in both 5% (1.3-fold) and 10% (1.6-fold) Dexa grafting, of which the best result was observed in PPIG5-Dexa 10% at C/P ratio of one. Discussion and conclusions: The modification of PPIs with Dexa is a promising approach to improve their cytotoxicity and transfection. The higher optimization of physicochemical characteristics, the better cell transfection and toxicity will be achieved.

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Section: Resultsmentioning

confidence: 99%

Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

Malaekeh‐Nikouei

Rezaee

Gholami

et al. 2018

Pharmaceutical Biology

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“…Clinically, only IT delivery is routinely used; however, the efficiency of this technique varies based on a number of drug-and patient-related factors. There [82] has been an explosion of research evaluating novel vehicles for therapeutic delivery to the inner ear such as liposomes, hydrogels, and nanoparticles [27,[88][89][90], and ultimately, identifying the optimal delivery vehicle will improve the yield on our ability to get targeted therapies to the specific biomarkers of interest. Once a delivery vehicle is optimized, ligands that specifically bind to the biomarker proteins of interest need to be developed.…”

Section: Discussionmentioning

confidence: 99%

Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

Naples

Miller

Ramsey

et al. 2019

Drug Deliv. and Transl. Res.

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The delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cellspecific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targetedinner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults.

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“…Dexamethasone reduced cell proliferation with increasing cell death. As a glucocorticosteroid with immunomodulatory and anti‐inflammation effects, it was expected that dexamethasone adjusted cytotoxicity (Malaekeh‐Nikouei et al, ; Yoon, Yang, Park, Kim, & Kim, ). In this case, dendrimers could not improve the solubility of drug significantly.…”

Section: Discussionmentioning

confidence: 99%

A comparative study on solubility improvement of tetracycline and dexamethasone by poly(propylene imine) and polyamidoamine dendrimers: An insight into cytotoxicity and cell proliferation

Najafi

Salami‐Kalajahi

Roghani‐Mamaqani

et al. 2019

J Biomedical Materials Res

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Many of new chemical discovered in pharmaceutical industry are hydrophobic compounds. Various techniques have been used to overcome solubility problems of hydrophobic drugs in aqueous media. In the meantime, dendrimers have been considered for sustainability, nanoscale size, high carry capacity, tunable terminal functional groups in terms of drug delivery and solubility. In this work, we have synthesized poly(propylene imine) (PPI) dendrimer up to fifth generation using reduction of nitrile groups after Michael addition and also, polyamidoamine (PAMAM) dendrimer up to fourth generation using Michael addition and amidation reactions. fourth and fifth generations of PPI dendrimer and fourth and third generations of PAMAM dendrimer in different concentrations were used to evaluate the solubility of two hydrophobic drugs (tetracycline and dexamethasone). Furthermore, cytotoxicity of dendrimers and dendrimers/drugs hybrids was studied. The results showed that with increasing concentrations and also the generation of dendrimers, the solubility of these two hydrophobic drugs was increased. Cytotoxicity study through MTT assay against Osteoblast-like cell line showed that dendrimers were relatively cytotoxic where adding dexamethasone caused higher cytotoxicity. However, tetracycline showed no significant effect on cytotoxicity whereas prevented cell proliferation. K E Y W O R D Scell proliferation, cytotoxicity, dendrimer, hydrophobic drug, solubility

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The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene delivery for inner ear therapy

Cited by 28 publications

References 31 publications

Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

Synthesis, characterization and evaluation of transfection efficiency of dexamethasone conjugated poly(propyleneimine) nanocarriers for gene delivery#

Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

A comparative study on solubility improvement of tetracycline and dexamethasone by poly(propylene imine) and polyamidoamine dendrimers: An insight into cytotoxicity and cell proliferation

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