Local drug delivery with a self-contained, programmable, microfluidic system

Fiering, Jason; Mescher, Mark J.; Swan, Erin E. Leary; Holmboe, Maria E.; Murphy, Brian; Chen, Z.; Peppi, Marcello; Sewell, William F.; McKenna, Michael J.; Kujawa, Sharon G.; Borenstein, Jeffrey T.

doi:10.1007/s10544-008-9265-5

Cited by 40 publications

(32 citation statements)

References 17 publications

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“…Such an exchange would cause marker loss from ST perilymph in the normal, RW compliant state. A comparable oscillatory fluid exchange across a cannula sealed into ST is used in a device to deliver drugs to perilymph (Fiering et al, 2009). Both of these interactions between perilymph and CSF in the basal turn of ST are incorporated into the computer model of the inner ear fluids that was used to interpret the results of gentamicin applications.…”

Section: Introductionmentioning

confidence: 99%

Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig

et al. 2016

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Intratympanic gentamicin therapy is widely used clinically to suppress the vestibular symptoms of Meniere’s disease. Dosing in humans was empirically established and we still know remarkably little about where gentamicin enters the inner ear, where it reaches in the inner ear and what time course it follows after local applications. In this study, gentamicin was applied to the round window niche as a 20 μL bolus of 40 mg/ml solution. Ten 2 μL samples of perilymph were collected sequentially from the lateral semi-circular canal (LSCC) at times from 1 – 4 hours after application. Gentamicin concentration was typically highest in samples originating from the vestibule and was lower in samples originating from scala tympani. To interpret these results, perilymph elimination kinetics for gentamicin was quantified by loading the entire perilymph space by injection at the LSCC with a 500 μg/ml gentamicin solution followed by sequential perilymph sampling from the LSCC after different delay times. This allowed concentration decline in perilymph to be followed with time. Gentamicin was retained well in scala vestibuli and the vestibule but declined rapidly at the base of scala tympani, dominated by interactions of perilymph with CSF, as reported for other substances. Quantitative analysis, taking into account perilymph kinetics for gentamicin, showed that more gentamicin entered at the round window membrane (57%) than at the stapes (35%) but the lower concentrations found in scala tympani were due to greater losses there. The gentamicin levels found in perilymph of the vestibule, which are higher than would be expected from round window entry alone, undoubtedly contribute to the vestibulotoxic effects of the drug. Furthermore, calculations of gentamicin distribution following targeted applications to the RW or stapes are more consistent with cochleotoxicity depending on the gentamicin concentration in scala vestibuli rather than that in scala tympani.

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Section: Introductionmentioning

confidence: 99%

Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig

et al. 2016

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“…Recently, however, application of novel technologies such as microfluidics or nanofluidics and biomimetics has emerged actuating drug delivery strategies. Microfluidics involves the engineering of a system to manipulate with high precision ultra-small volumes, such as nanoliters of liquids (108). Microfluidic technology will facilitate screening of nanodrug delivery systems in a high throughput fashion for well-controlled, batch-to-batch reproducible fabrication of nanoparticles and assess their biological behavior for biomedical applications (109).…”

Section: Emerging Technologies May Accelerate Translation Of Nanopartmentioning

confidence: 99%

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

et al. 2014

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Abstract. Nanotechnology has enabled the development of novel therapeutic and diagnostic strategies, such as advances in targeted drug delivery systems, versatile molecular imaging modalities, stimulus responsive components for fabrication, and potential theranostic agents in cancer therapy. Nanoparticle modifications such as conjugation with polyethylene glycol have been used to increase the duration of nanoparticles in blood circulation and reduce renal clearance rates. Such modifications to nanoparticle fabrication are the initial steps toward clinical translation of nanoparticles. Additionally, the development of targeted drug delivery systems has substantially contributed to the therapeutic efficacy of anti-cancer drugs and cancer gene therapies compared with nontargeted conventional delivery systems. Although multifunctional nanoparticles offer numerous advantages, their complex nature imparts challenges in reproducibility and concerns of toxicity. A thorough understanding of the biological behavior of nanoparticle systems is strongly warranted prior to testing such systems in a clinical setting. Translation of novel nanodrug delivery systems from the bench to the bedside will require a collective approach. The present review focuses on recent research efforts citing relevant examples of advanced nanodrug delivery and imaging systems developed for cancer therapy. Additionally, this review highlights the newest technologies such as microfluidics and biomimetics that can aid in the development and speedy translation of nanodrug delivery systems to the clinic.

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“…In the most severe cases, patients suffering from these conditions are implanted with commercially-available drug infusion pumps for therapeutic management. These devices bypass physiological barriers to enable delivery of new compounds such as biologics, biosimilars, and other small molecules directly to the target tissue (Urquhart et al 1984;Urquhart 2001); and thereby maximize therapeutic efficacy of the drug and limiting toxic side effects by delivering the correct amount of drug in the vicinity of the target cells and reducing the drug exposure to the nontarget cells (Fiering et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors

Sheybani

Cobo

Meng

2015

Biomed Microdevices

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We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 μL/min) and dose sensing (bolus resolution of 0.55-2 μL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue.

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Local drug delivery with a self-contained, programmable, microfluidic system

Cited by 40 publications

References 17 publications

Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig

Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors

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