Biocompatibility and Therapeutic Effect of 3 Intra-Tympanic Drug Delivery Vehicles in Acute Acoustic Trauma

2020 ◽  
Vol 25 (6) ◽  
pp. 291-296
Author(s):  
Mina Park ◽  
Yu-Jung Hwang ◽  
Tae-Soo Noh ◽  
Shin-Wook Woo ◽  
Ji-Hoon Park ◽  
...  

<b><i>Introduction:</i></b> The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. <b><i>Materials and Methods:</i></b> After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (<i>n</i> = 15), hyaluronic acid (HA) + D (<i>n</i> = 17), and methoxy polyethylene glycol-<i>b</i>-polycaprolactone block copolymer (MP) + D (<i>n</i> = 24). <b><i>Results:</i></b> No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (&#x3c;1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. <b><i>Discussion/Conclusion:</i></b> HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

2021 ◽  
Vol 22 (11) ◽  
pp. 5720
Author(s):  
Jung-Ah Cho ◽  
Bong-Jik Kim ◽  
Yu-Jung Hwang ◽  
Shin-Wook Woo ◽  
Tae-Soo Noh ◽  
...  

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.


2018 ◽  
Vol 18 (5) ◽  
pp. 439-457 ◽  
Author(s):  
Merina Mariyam ◽  
Kajal Ghosal ◽  
Sabu Thomas ◽  
Nandakumar Kalarikkal ◽  
Mahima S. Latha

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 427
Author(s):  
Amin Mirzaaghasi ◽  
Yunho Han ◽  
So-Hee Ahn ◽  
Chulhee Choi ◽  
Ji-Ho Park

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.


Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3589
Author(s):  
Rui Liu ◽  
Alessandro Poma

Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.


2021 ◽  
pp. e00663
Author(s):  
Tarun Mateti ◽  
Surabhi Aswath ◽  
Anoop Kishore Vatti ◽  
Agneya Kamath ◽  
Anindita Laha

RSC Advances ◽  
2021 ◽  
Vol 11 (21) ◽  
pp. 13014-13023
Author(s):  
Mark B. Frampton ◽  
Andrea Blais ◽  
Zachary Raczywolski ◽  
Alan Castle ◽  
Paul M. Zelisko

Hybrid siloxane-phosphocholines (SiPCs) are a unique class of lipids that spontaneously form unilamellar vesicles (ULVs) that are ∼100 nm in diameter upon exposure to aqueous media without the need for extrusion and can be used as delivery vehicles.


2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.


2015 ◽  
Vol 798 ◽  
pp. 60-69 ◽  
Author(s):  
Daniel G. Pruitt ◽  
Sara M. Baumann ◽  
Gregory J. Place ◽  
Agozie N. Oyeamalu ◽  
Ekkehard Sinn ◽  
...  

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