Inner Ear Therapeutics: An Overview of Middle Ear Delivery

Patel, Jaimin; Szczupak, Mikhaylo; Rajguru, Suhrud M.; Balaban, Carey D.; Hoffer, Michael E.

doi:10.3389/fncel.2019.00261

Cited by 26 publications

(24 citation statements)

References 58 publications

(77 reference statements)

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“…1 Middle ear targeted drug delivery is challenging because of the presence of the tympanic membrane, which is considered the first barrier that resists drug entry to the middle and inner ear. 2 Therefore, to achieve an efficient middle ear drug delivery, drugs should have a sufficient ability to diffuse through the intact tympanic membrane. 3 As both the tympanic membrane and the middle ear are considered highly perfused tissues, the aural drug administration can provide the right choice for local and systemic drug delivery.…”

Section: Introductionmentioning

confidence: 99%

<p>Formulation and Characterization of Cinnarizine Targeted Aural Transfersomal Gel for Vertigo Treatment: A Pharmacokinetic Study on Rabbits</p>

Abdelmonem¹,

Hamed²,

Abdel-Halim³

et al. 2020

IJN

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Introduction and Aim: Cinnarizine is indicated orally for treating vertigo associated with Ménière's syndrome and has a local anesthetic effect as well. The present study aims to develop an aural Cinnarizine mucoadhesive transfersomal gel to overcome the first-pass metabolism. Methods: Eighteen Cinnarizine transfersomes were prepared by the thin-film hydration technique using different types of phosphatidylcholine and edge activators in different ratios. Formulae were tested for their appearance, entrapment efficiency, and in-vitro drug release after eight hours. F1, F4, F7, F9, F10, and F12 were selected to be examined for particle size, polydispersity index, and zeta potential. According to the previous parameters, F1 and F10 were incorporated into gels using different polymers according to factorial design 23. The eight gels were tested for appearance, pH, mucoadhesion, spreadability, drug content, in-vitro drug release after eight hours, and rheology. The transfersomal gel F1A was subjected to FTIR analysis and in-vivo pharmacokinetic study. Results: The transfersomal dispersion colors were ranging between the white and yellow. Their EE % ranged from 64.36±1.985% to 94.09±1.74%, and their in-vitro release percentages were between 61.82±1.92% and 95.92±1.18%. Also, the vesicles PS ranged from 212.3 ±30.05nm to 2150±35.35nm, DI from 0.238±0.134 to 1±0.00 and zeta potential from −57.5 ±2.54 to +4.73±1.57 mV. The transfersomal gels showed pseudoplastic behavior, pH range of 5.5 to 8, a mucoadhesive force of 169.188±1.26 to 321.212±6.94 (dyne/cm 2 ×10 2), spreadability of 40 ±7.03mm to 138 ±3.77mm, and in-vitro drug release of 81.63±1.128% to 97.78 ±0.102%. The IR spectra of the (drug-excipients) physical mixture revealed that there were no shifts of incompatibility. The in-vivo pharmacokinetic study illustrated that [AUC] 0-24 of F1A was significantly higher than that of tablets at (P< 0.05), equivalent to 703.563±26.470 and 494.256±9.621ɲg.hr/mL respectively. Conclusion: The study revealed that Cinnarizine aural mucoadhesive targeted delivery provides an improved systemic bioavailability over the conventional oral route.

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Section: Introductionmentioning

confidence: 99%

<p>Formulation and Characterization of Cinnarizine Targeted Aural Transfersomal Gel for Vertigo Treatment: A Pharmacokinetic Study on Rabbits</p>

Abdelmonem¹,

Hamed²,

Abdel-Halim³

et al. 2020

IJN

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“…Moreover, the round window membrane (RWM) may not be as strictly regulated as the blood brain barrier (BBB). Recent reviews indicate that the RWM behaves as if it is semi-permeable and even has microvilli on its apical surface which speaks to its absorptive properties [97]. These findings suggest that MSCs have the ability to penetrate tight barriers such blood labyrinth barriers (BLB), and potentially the round window membrane (RWM), to reach the cochlear sensory compartment.…”

Section: Discussionmentioning

confidence: 99%

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

Eshraghi

Ocak

Zhu

et al. 2020

JCM

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Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

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“…Drawbacks are clearance of the compound by the Eustachian tube and restricted diffusion through the round window membrane. Efficiency of the approach can be enhanced by applying compounds in biodegradable wicks or (hydro-)gels increasing their residence time in the middle ear as well as utilizing nanocarriers, which enhance permeation through the round window membrane [86] . Intracochlear injection targeting scala tympani via the round window membrane is the most commonly used route of administration in current preclinical studies.…”

Section: Disease Mechanismsmentioning

confidence: 99%