Development of thermosensitive poloxamer 407-based microbubble gel with ultrasound mediation for inner ear drug delivery

Hearing loss is one of the most common disabilities affecting both children and adults worldwide. However, traditional treatment of hearing loss has some limitations, particularly in terms of drug delivery system as well as diagnosis of ear imaging. The blood–labyrinth barrier (BLB), the barrier between the vasculature and fluids of the inner ear, restricts entry of most blood-borne compounds into inner ear tissues. Nanoparticles (NPs) have been demonstrated to have high biocompatibility, good degradation, and simple synthesis in the process of diagnosis and treatment, which are promising for medical applications in hearing loss. Although previous studies have shown that NPs have promising applications in the field of inner ear diseases, there is still a gap between biological research and clinical application. In this paper, we aim to summarize developments and challenges of NPs in diagnostics and treatment of hearing loss in recent years. This review may be useful to raise otology researchers’ awareness of effect of NPs on hearing diagnosis and treatment.

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Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

Current Molecular Pharmacology ◽

10.2174/1874467214666210120160016 ◽

2021 ◽

Vol 14 ◽

Author(s):

Sarbjot Kaur ◽

Ujjwal Nautiyal ◽

Pooja A. Chawla ◽

Viney Chawla

Keyword(s):

Drug Delivery ◽

Ex Vivo ◽

In Vitro Release ◽

Nanostructured Lipid Carriers ◽

Polydispersity Index ◽

Poloxamer 407 ◽

Ex Vivo Permeation ◽

Permeation Studies ◽

Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

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A Totally Implantable Drug Delivery System for Local Therapy of the Middle and Inner Ear

Ear Nose & Throat Journal ◽

10.1177/014556139707600813 ◽

1997 ◽

Vol 76 (8) ◽

pp. 567-570 ◽

Cited By ~ 15

Author(s):

Rolf Lehner ◽

Heribert Brugger ◽

Marcus M. Maassen ◽

Hans-Peter Zenner

Keyword(s):

Drug Delivery ◽

Inner Ear ◽

Drug Delivery System ◽

Delivery System ◽

Drug Application ◽

Local Therapy ◽

Trophic Factors ◽

Mastoid Cavity ◽

Round Window Membrane ◽

Wide Range

Local therapy of middle and inner ear diseases is being used, but is restricted to cases of ear drum perforation or to repeated invasive intratympanic drug application by the physician. In accordance with the Medical Device Directive (class III), a bone-anchored, totally implantable drug delivery system (TI-DDS) has been developed. It includes a micropump for subcutaneous, patient-controlled activation, a drug reservoir and a septum port. A thin guide-wired catheter leads from the pump outlet to the point of application in the mastoid or middle ear cavities. Local inner ear therapy with suitable drugs is possible by positioning the catheter's end near the round window membrane. The system requires no battery and will offer a wide range of patient-controlled bolus applications (25 μl per activation). We first analyzed the three-dimensional implantation geometry of the mastoid cavity. Basic micromechanical problems have been solved in order to create several prototypes. The TI-DDS has already undergone extensive in vitro testing. Recent results of pump rate precision and digital pressure force testing are promising. Local drug treatment for conditions such as lidocaine-sensitive tinnitus, secretory otitis media, Meniere's disease, localized pain and intralesional cancer is under discussion. Furthermore, local application of future biotechnological trophic factors for inner ear treatment is anticipated. The basic engineering is completed and initial animal tests are in preparation.

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Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

Pharmaceutics ◽

10.3390/pharmaceutics11020058 ◽

2019 ◽

Vol 11 (2) ◽

pp. 58 ◽

Cited By ~ 5

Author(s):

Dong Shin ◽

Bo Chae ◽

Yoon Goo ◽

Ho Yoon ◽

Chang Kim ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Bioavailability ◽

Amorphous State ◽

Poloxamer 407 ◽

Enhanced Dissolution ◽

Previous Formulation ◽

Practical Development ◽

Precipitation Inhibitor

To improve the dissolution and oral bioavailability of valsartan (VST), we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMED) composed of Capmul® MCM (oil), Tween® 80 (surfactant), Transcutol® P (cosurfactant), and Poloxamer 407 (precipitation inhibitor) but encountered a stability problem (Transcutol® P-induced weight loss in storage) after solidification. In the present study, replacing Transcutol® P with Gelucire® 44/14 resulted in a novel SuSMED formulation, wherein the total amount of surfactant/cosurfactant was less than that of the previous formulation. Solidified SuSMED (S-SuSMED) granules were prepared by blending VST-containing SuSMED with selective solid carriers, L-HPC and Florite® PS-10, wherein VST existed in an amorphous state. S-SuSMED tablets fabricated by direct compression with additional excipients were sufficiently stable in terms of drug content and impurity changes after 6 months of storage at accelerated conditions (40 ± 2 °C and 75 ± 5% relative humidity). Consequently, enhanced dissolution was obtained (pH 1.2, 2 h): 6-fold for S-SuSMED granules against raw VST; 2.3-fold for S-SuSMED tablets against Diovan® (reference tablet). S-SuSMED tablets increased oral bioavailability in rats (10 mg/kg VST dose): approximately 177–198% versus raw VST and Diovan®. Therefore, VST-loaded S-SuSMED formulations might be good candidates for practical development in the pharmaceutical industry.

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