Packaging for a drug delivery microelectromechanical system

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2005.Includes bibliographical references (p. 52-55).Local drug delivery is a fast expanding field, and has been a center of attention for researchers in medicine in the last decade. Its advantages over systemic drug delivery are clear in cancer therapy, with localized tumors. A silicon microelectromechanical drug delivery device was fabricated for the purpose of delivering chemotherapeutic agents such-as carmustine, a potent brain cancer drug, directly to the site of the tumor. Limitations in the delivery capacity of the device led to the design of a new package. This package is made from thermally bonded Pyrex® 7740 frames that are anodically bonded to the drug delivery chip. It increases the capacity of the chip, is smaller than the previous package and possesses true hermeticity, because of the bonding processes involved. This work describes the fabrication steps of the new package and a problem with the thermal bonding of Pyrex® frames preventing the achievement of a package true to the original design. A temporary solution was devised and the completed package was tested with regards to its intended goals. It managed to increase the load capacity of the chip by a, factor of 10, with potential for more, while decreasing the overall size of the package. Short-term hermeticity was achieved for this package by using a UV-cured epoxy to bond some pieces, which was not in the original design. Future work will focus on finding a permanent solution to the aforementioned problem, and directions for it were suggested.by Hong Linh Ho Duc.S.M

Emergency delivery of Vasopressin from an implantable MEMS rapid drug delivery device

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references.An implantable rapid drug delivery device based on micro-electro-mechanical systems (MEMS) technology was designed, fabricated and validated for the in vivo rapid delivery of vasopressin in a rabbit model. In vitro characterization of device performance found the device capable of reliably and reproducibly delivering 85% of its loaded drug solution. A comparison of intraperitoneal and subcutaneous injections of vasopressin in rabbits was performed to determine the implantation location for the device. Both routes of delivery were found to be viable implantation locations, and the less invasive subcutaneous site was chosen. Vasopressin was released from the subcutaneously implanted device in anesthetized rabbits and found to exert a measurable effect on blood pressure. The bioavailability of vasopressin delivered from the device was found to be 6.2% after one hour. Proof-of-concept experiments were also conducted to address long-term stability of drugs in the implanted device and wireless activation of the device. These experiments defined areas of future research for improvement of the device.by Hong Linh Ho Duc.Ph.D

In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability

In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

An Implantable MEMS Drug Delivery Device for Rapid Delivery in Ambulatory Emergency Care

We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD[superscript 3] (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD3 provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD3 are proposed

Pial arteriovenous fistula associated with vein of Galen dilatation in adult: A case report and MRI findings

Pial arteriovenous fistula (PAVF) is a rare intracranial vascular lesion where direct communication exists between one or more pial arteries and a cerebral vein, without an intervening nidus and located in the subpial meningeal space. When the drainage of PAVF involves a dilated, but already formed vein of Galen (VOG), it should be distinguished from other vascular lesions located in this area, because their angio-architecture, natural history and treatment options are different. A 33-year-old female was admitted to our hospital with a history of new-onset generalized tonic-clonic seizures. Clinical examination showed no neurological deficit. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) depicted an arteriovenous fistula that was fed by the pial branches from left posterior cerebral artery and drained into the medial atrial vein before joining the VOG confluence and causing VOG dilatation. No nidus between the feeding arteries and draining vein, dural feeding arteries, or anatomical variations commonly seen with true vein of Galen aneurysmal malformations (VOGM) were found. These finding suggested a diagnosis of a PAVF associated with vein of Galen dilatation, which was confirmed by digital subtraction angiography. The patient was treated with transarterial glue embolization in 1 section, resulting in nearly complete occlusion of the fistula. Conventional MRI and MRA are noninvasive modalities that can provide valuable information regarding the anatomic localization of the fistula point, the feeding arteries, the venous sac, and their relationship with surrounding structures. These techniques are helpful for accurate diagnosis and treatment planning

Xanthine oxidase, α-glucosidase and α-amylase inhibitory activities of the essential oil from Piper lolot: In vitro and in silico studies

Introduction: Piper lolot is a species of herb used as a popular food in Vietnam. Furthermore, the species has been used as a Vietnamese traditional medicine to treat many diseases. Methods: Chemical constituents in the essential oil from leaves of Piper lolot were determined using GC/MS analysis. The anti-gout and anti-diabetic activities of the essential oil were determined through the inhibitory assays against xanthine oxidase, α-glucosidase and α-amylase enzymes. In addition, molecular docking simulations were used to elucidate the inhibitory mechanism between the main compounds and the enzymes. Results: The dominant constituents of the Piper lolot essential oils were determined as β-caryophyllene (20.6%), β-bisabolene (11.6%), β-selinene (8.4%), β-elemene (7.7%), trans-muurola-4(14),5-diene (7.4%), and (E)-β-ocimene (6.7%). The essential oil displayed xanthine oxidase, α-amylase, and α-glucosidase inhibitory activities with IC50 values of 28.4, 130.6, and 59.1 μg/mL, respectively. The anti-gout and anti-diabetic activities of the essential oil from the P. lolot species are reported for the first time. Furthermore, molecular docking simulation was consistent to in vitro experiments. Conclusion: The present study provides initial evidence that the essential oil of P. lolot may be a potential natural source to develop new diabetes preparations

Design of Silicon TE0/TE1 Mode Router Using Mach-Zehnder and Multimode Interferometers

This paper proposes a new design of two-mode three-port optical mode router for mode division multiplexing systems. The device consists of a Mach-Zehnder interferometer (MZI) and a multimode interferometer (MMI), which utilizes silicon material for photonic integrated circuits (PIC). By setting appropriate values for the two butterfly-shaped phase shifters (PSs) at MZI and MMI, the input mode, either transverse electric (TE) modes TE0 or TE1, can be routed to the desired output among the three output ports. The device is designed and optimized via three-dimensional beam propagation method (3D BPM). The proposed device achieves very low insertion loss and small cross-talk, which are less than 0.4 dB and -24.5 dB, respectively, over the whole C band

Evaluation of Two Techniques for Viral Load Monitoring Using Dried Blood Spot in Routine Practice in Vietnam (French National Agency for AIDS and Hepatitis Research 12338)

International audienceBackground. Although it is the best method to detect early therapeutic failure, viral load (VL) monitoring is still not widely available in many resource-limited settings because of difficulties in specimen transfer, personnel shortage, and insufficient laboratory infrastructures. Dried blood spot (DBS) use, which was introduced in the latest World Health Organization recommendations, can overcome these difficulties. This evaluation aimed at validating VL measurement in DBS, in a laboratory without previous DBS experience and in routine testing conditions.Methods. Human immunodeficiency virus (HIV)-infected adults were observed in a HIV care site in Hanoi, and each patient provided 2 DBS cards with whole blood spots and 2 plasma samples. Viral load was measured in DBS and in plasma using the COBAS Ampliprep/TaqMan and the Abbott RealTime assays. To correctly identify those with VL ≥ 1000 copies/mL, sensitivity and specificity were estimated.Results. A total of 198 patients were enrolled. With the Roche technique, 51 plasma VL were ≥1000 copies/mL; among these, 28 presented a VL in DBS that was also ≥1000 copies/mL (sensitivity, 54.9; 95% confidence interval [CI], 40.3-68.9). On the other hand, all plasma VL < 1000 copies/mL were also <1000 copies/mL in DBS (specificity, 100; 95% CI, 97.5-100). With the Abbott technique, 45 plasma VL were ≥1000 copies/mL; among these, 42 VL in DBS were also ≥1000 copies/mL (sensitivity, 93.3%; 95% CI, 81.7-98.6); specificity was 94.8 (95% CI, 90.0-97.7).Conclusions. The Abbott RealTime polymerase chain reaction assay provided adequate VL results in DBS, thus allowing DBS use for VL monitoring