Comparison of Drug Distribution Between Intravitreal Injection and a Controlled–Release Implant in a Rabbit Eye

Abstract Due to physiological barriers within the eye, which limit penetration of many drugs from the systemic circulation into the vitreous, the most common method of treating retinal disease is direct intravitreal injection. However, this common procedure may be inappropriate for a wide range of drugs as it may lead to highly variable concentrations potentially causing higher toxicity for tissues inside the eye and limiting therapeutic effect. A recent procedure is to use surgically implanted drug release device, called implant here, in the vitreous of the eye that allow controlled release of drug over a sustained period of time. For constant release of drug over 15 hours, a substantial reduction in peak drug concentration is predicted near the retina. When compared with the implant, a doubling of drug concentration would be expected for more than 3 hours near the retina for the intravitreal injection.

Download Full-text

Microsponges: A Novel Strategy to Control the Delivery Rate of Active Agents with Reduced Skin Irritancy

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i6-s.3757 ◽

2019 ◽

Vol 9 (6-s) ◽

pp. 238-247

Author(s):

PRAMILA VISHWAKARMA ◽

Ramraj Choudhary

Keyword(s):

Drug Delivery ◽

Controlled Release ◽

Drug Delivery System ◽

Delivery System ◽

Skin Irritation ◽

Systemic Circulation ◽

Release Mechanism ◽

Porous Microspheres ◽

Wide Range ◽

Novel Strategy

Microsponges are particulate system which is composed by porous polymeric material. As compare to Conventional topical formulations, microsponge provide controlled release of the drug in the epidermis, it is to ensure that the drug is mainly localized and does not unduly entering the systemic circulation, it is a new area of research. The active ingredient needs to maximize the time to stay on the skin, while reducing transdermal penetration. Apart from this, there is a problem of unethical vehicles that can be viscous sticky deformation and skin irritation. One of the biggest challenges of now a days is to control irritability for a predetermined site of active agents in the human body. Microsponges delivery system is a unique technique for controlled release with low irritant involving many triggers of Mechanism for the release of drugs. The Microsponge Delivery system is a polymeric porous microspheres, which can trap a wide range of effective elements such as anti-fungus, anti-infected, anti- inflammatory agent, fragrance and essential agent. This review includes different techniques used to prepare microsponges, formulation consideration, safety consideration, drug release mechanism, and challenges with microsponge drug delivery system along with their advantages, disadvantages and applications. In the current review, we summarize the updated application and capacity of Microsponge as an effective drug-delivery system to reduce skin irritation. Keywords: Microsponges; quasi-emulsion solvent diffusion; Porous microspheres; Controlled release.

Download Full-text

Microsponges: An Overview

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v4i4.8860 ◽

2017 ◽

Vol 4 (4) ◽

Author(s):

Hamid Hussain ◽

Divya Juyal ◽

Archana Dhyani

Keyword(s):

Controlled Release ◽

Delivery System ◽

Oral Delivery ◽

Active Agent ◽

Topical Delivery ◽

Water Soluble ◽

Wide Range ◽

Porous Beads

Microsponge and Nanosponge delivery System was originally developed for topical delivery of drugs can also be used for controlled oral delivery of drugs using water soluble and bioerodible polymers. Microsponge delivery system (MDS) can entrap wide range of drugs and then release them onto the skin over a time by difussion mechanism to the skin. It is a unique technology for the controlled release of topical agents and consists of nano or micro porous beads loaded with active agent and also use for oral delivery of drugs using bioerodible polymers.

Download Full-text

Clinical Perspectives and Trends: Microperimetry as a trial endpoint in retinal disease

Ophthalmologica ◽

10.1159/000515148 ◽

2021 ◽

Author(s):

Yesa Yang ◽

Hannah Dunbar

Keyword(s):

Clinical Trial ◽

Retinal Disease ◽

Age Related Macular Degeneration ◽

Gene Therapies ◽

Age Related ◽

Wide Range ◽

Trial Endpoints ◽

Visual Acuity Loss ◽

Psychophysical Test ◽

Trial Endpoint

Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting early stages of common sight-threatening conditions such as age-related macular degeneration. Visual function measures are likely to be key candidates in this search. Over the last two decades, microperimetry has been used extensively to characterize functional vision in a wide range of retinal conditions, detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicenter trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical issues to consider, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.

Download Full-text

Online Thread and Data Mapping Using a Sharing-Aware Memory Management Unit

ACM Transactions on Modeling and Performance Evaluation of Computing Systems ◽

10.1145/3433687 ◽

2021 ◽

Vol 5 (4) ◽

pp. 1-28

Author(s):

Eduardo H. M. Cruz ◽

Matthias Diener ◽

Laércio L. Pilla ◽

Philippe O. A. Navaux

Keyword(s):

Energy Efficiency ◽

Memory Management ◽

Substantial Reduction ◽

Management Unit ◽

Memory Access ◽

Parallel Applications ◽

Data Mapping ◽

Wide Range ◽

Memory Accesses ◽

Level Parallelism

Current and future architectures rely on thread-level parallelism to sustain performance growth. These architectures have introduced a complex memory hierarchy, consisting of several cores organized hierarchically with multiple cache levels and NUMA nodes. These memory hierarchies can have an impact on the performance and energy efficiency of parallel applications as the importance of memory access locality is increased. In order to improve locality, the analysis of the memory access behavior of parallel applications is critical for mapping threads and data. Nevertheless, most previous work relies on indirect information about the memory accesses, or does not combine thread and data mapping, resulting in less accurate mappings. In this paper, we propose the Sharing-Aware Memory Management Unit (SAMMU), an extension to the memory management unit that allows it to detect the memory access behavior in hardware. With this information, the operating system can perform online mapping without any previous knowledge about the behavior of the application. In the evaluation with a wide range of parallel applications (NAS Parallel Benchmarks and PARSEC Benchmark Suite), performance was improved by up to 35.7% (10.0% on average) and energy efficiency was improved by up to 11.9% (4.1% on average). These improvements happened due to a substantial reduction of cache misses and interconnection traffic.

Download Full-text

Reduced heart rate variability during sleep in long-duration spaceflight

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00423.2012 ◽

2013 ◽

Vol 305 (2) ◽

pp. R164-R170 ◽

Cited By ~ 15

Author(s):

D. Xu ◽

J. K. Shoemaker ◽

A. P. Blaber ◽

P. Arbeille ◽

K. Fraser ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Substantial Reduction ◽

Space Station ◽

Power Spectral Analysis ◽

Power Spectral ◽

Long Duration ◽

Fractal Properties ◽

Wide Range ◽

Simultaneous Movement

Limited data are available to describe the regulation of heart rate (HR) during sleep in spaceflight. Sleep provides a stable supine baseline during preflight Earth recordings for comparison of heart rate variability (HRV) over a wide range of frequencies using both linear, complexity, and fractal indicators. The current study investigated the effect of long-duration spaceflight on HR and HRV during sleep in seven astronauts aboard the International Space Station up to 6 mo. Measurements included electrocardiographic waveforms from Holter monitors and simultaneous movement records from accelerometers before, during, and after the flights. HR was unchanged inflight and elevated postflight [59.6 ± 8.9 beats per minute (bpm) compared with preflight 53.3 ± 7.3 bpm; P < 0.01]. Compared with preflight data, HRV indicators from both time domain and power spectral analysis methods were diminished inflight from ultralow to high frequencies and partially recovered to preflight levels after landing. During inflight and at postflight, complexity and fractal properties of HR were not different from preflight properties. Slow fluctuations (<0.04 Hz) in HR presented moderate correlations with movements during sleep, partially accounting for the reduction in HRV. In summary, substantial reduction in HRV was observed with linear, but not with complexity and fractal, methods of analysis. These results suggest that periodic elements that influence regulation of HR through reflex mechanisms are altered during sleep in spaceflight but that underlying system complexity and fractal dynamics were not altered.

Download Full-text

Engineering and experimental testing of two-wavelength laser-assisted device for photocoagulation of eye tissue

Ophthalmology journal ◽

10.17816/ov2013210-15 ◽

2013 ◽

Vol 6 (2) ◽

pp. 10-15

Author(s):

Yury Sergeevich Astakhov ◽

Yevgeny Leonidovich Akopov ◽

Aleksandr Anatolevich Ivanov ◽

Mariya Alexeevna Smirnova ◽

Leonid Nikolaevich Panteleev ◽

...

Keyword(s):

High Efficiency ◽

Experimental Testing ◽

Wide Spectrum ◽

Retinal Disease ◽

Primary Objective ◽

3D Analysis ◽

Potential Candidate ◽

Living Tissue ◽

Wide Range ◽

Retinal Photocoagulation

Retinal photocoagulation is believed to be one of most efficient methods to treat many retinal abnormalities. By now, a number of lasers operating at different wavelengths, irradiation intensities, and exposure times have been tested in search of optimal parameters for each type of retinal photocoagulation. Taking into consideration a wide range of such parameters, the primary objective of the present study was to develop a device that would combine the potentials of different lasers into a single universal laser-assisted coagulator (ULAC) equally suitable for a wide diversity of retinal disease. Important issue would be the creation of an experimental model allowing an operative evaluation of the coagulating effect induced by the ULAC. The sources of coherent irradiation to be combined were DPSS and diode lasers (532 and 810 nm, respectively). Through two individual fibers, irradiation generated by each of the lasers entered the optical blender to be further directed to the target, now via a single fiber. The target termed the “surrogate of living tissue” was a mixture of donor human blood and chicken egg white, which corresponded, respectively, to the chromophore and thermocoagulating agent, both sensitive to laser beams at 532 and 810 nm. As a result, irradiation of surrogate of living tissue by a laser under the trial caused the formation of a coagulate and its firm adhesion to the coverslip, after that the coagulate was separated from the unaffected surrogate of living tissue followed by its 3D-analysis. In conclusion, the whole procedure, while being relatively non-expensive and easy to perform, has proved to be simple enough for testing of a wide spectrum of coagulation-inducing parameters, whatever laser was used. Moreover, even the initial experiments have shown the high efficiency of the ULAC as a potential candidate for the application in ophthalmological practice.

Download Full-text

Numerical Investigation of Drug Transport from Blood Vessels to Tumor Tissue Using a Tumor-Vasculature-on-a-Chip

10.1101/652099 ◽

2019 ◽

Author(s):

Wei Li ◽

Hao-Fei Wang ◽

Zhi-Yong Li ◽

Tong Wang ◽

Chun-Xia Zhao

Keyword(s):

Tumor Microenvironment ◽

Blood Vessel ◽

Drug Concentration ◽

Tumor Size ◽

Drug Transport ◽

Tumor Tissue ◽

Transport Model ◽

Temporal Structure ◽

Drug Distribution ◽

Tumor Vasculature

AbstractThe delivery of adequate concentration of anticancer drugs to tumor site is critical to achieve effective therapeutic treatment, but it is challenging to experimentally observe drug transport and investigate the spatial distribution of the drug in tumor microenvironment. In this study, we investigated the drug transport from a blood vessel to tumor tissue, and explored the effect of tumor size, tumor numbers and positioning on drug concentration distribution using a numerical method in combination with a microfluidic Tumor-Vasculature-on-a-Chip (TVOC) model. The TVOC model is composed of a vessel channel, a tumor channel sandwiched with a porous membrane. A species transport model based on computational fluid dynamics was adapted to investigate drug transport. The numerical simulation was firstly validated using experimental data, and then used to analyse the spatial-temporal structure of the flow, and to investigate the effect of tumor size and positioning on drug transport and drug concentration heterogeneity. We found the drug concentration surrounding the tumor is highly heterogeneous, with the most downstream point the most difficult for drugs to transport and the nearest point to the blood vessel the easiest. Moreover, tumor size and positioning contribute significantly to this drug concentration heterogeneity on tumor surface, which is dramatically augmented in large and downstream-positioned tumors. These studies established the relationship between solid tumor size/positioning and drug concentration heterogeneity in the tumor microenvironment, which could help to understand heterogenous drug distribution in tumor microenvironment.

Download Full-text

Post colonoscopic acute bacterial prostatitis: a case report

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20211889 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1482

Author(s):

Rahim A. Rashid ◽

Ramalakshmi Karthikeyan

Keyword(s):

Urinary Tract ◽

Lower Urinary Tract ◽

Bacterial Infections ◽

Common Procedure ◽

Lower Urinary Tract Infection ◽

Delayed Treatment ◽

Bacterial Prostatitis ◽

Wide Range ◽

Acute Bacterial Prostatitis ◽

Lower Urinary

Colonoscopy is a common procedure for diagnosing a wide range of conditions and symptoms affecting the large bowel. Research has shown that the examination itself may induce transient bacterial infections. Specifically acute bacterial prostatitis (ABP) has little mention in medical literature as a recognized complication of this procedure. Here we discuss a 37 year old male presenting with symptoms suggesting lower urinary tract infection after having undergone colonoscopy followed by recurrent episodic haematuria and lower urinary tract symptoms (LUTS). Physicians and endoscopists should be aware of the risk of acute bacterial prostatitis as a potential complication of colonoscopy in order to minimize misdiagnosis as well as the complications associated with the delayed treatment of it. In addition male patients and the immunocompromised should be fully counselled regarding this risk prior to undertaking this procedure.

Download Full-text

Design and physics basis for the upcoming DIII-D SAS-VW campaign to quantify tungsten leakage and transport in a new slot divertor geometry

Physica Scripta ◽

10.1088/1402-4896/ac3c5f ◽

2021 ◽

Author(s):

Tyler Abrams ◽

Gregory Sinclair ◽

J.H. Nichols ◽

Ezekial A Unterberg ◽

David Donovan ◽

...

Keyword(s):

Temporal Resolution ◽

Small Angle ◽

Stress Test ◽

Substantial Reduction ◽

Wide Range ◽

Experiment Validation

Abstract A set of experiments are planned to exploit the high SOL collisionality enabled by a tightly baffled slot divertor geometry to suppress tungsten leakage in DIII-D. A toroidal row of graphite tiles from the Small Angle Slot (SAS) divertor is being coated with 10-15 µm of tungsten. New spectroscopic viewing chords with in-vacuo optics will measure the W gross erosion source from the divertor surface with high spatial and temporal resolution. In parallel, the bottom of the SAS divertor is changed from a flat to a "V" shape. New SOLPS-ITER/DIVIMP simulations conducted with drifts using the planned "V" shape predict a substantial reduction in W sourcing and SOL accumulation in either B×∇B direction relative to either the old SAS divertor shape or the open, lower divertor. Dedicated studies are planned to carefully characterize the level of W sourcing, leakage, and scrape-off-layer (SOL) accumulation in DIII-D over a wide range of plasma scenarios. Various actuators will be assessed for their efficacy in further reducing high-Z impurity sources and leakage from the slot divertor geometry. This coupled code-experiment validation effort will be used to stress-test physics models and build confidence in extrapolations to advanced, high-Z divertor geometries for next-step devices.

Download Full-text