The pursuit of linear dosage in pharmacy: reservoir-based drug delivery systems from macro to micro scale.

Introduction: The pursuit of linear dosage in pharmacy is essential for achieving consistent therapeutic release and enhancing patient compliance. This review provides a comprehensive summary of zero-order drug delivery systems, with a particular focus on reservoir-based systems emanated from different microfabrication technologies.

Areas Covered: The consideration of recent advances in drug delivery systems is given to encompass the key areas including the importance of achieving a constant drug release rate for therapeutic applications.

Template-Free Manufacturing of Defined Structure and Size Polymeric Microparticles.

Complex-structured polymeric microparticles hold significant promise as an advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape, and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or limited control over particle size distribution and cargo (functional payload) release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters.

Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency in vitro and in vivo.

Photoacoustic flow cytometry is one of the most effective approaches to detect "alien" objects in the bloodstream, including circulating tumor cells, blood clots, parasites, and emboli. However, the possibility of detecting high-amplitude signals from these objects against the background of blood depends on the parameters of the laser pulse. So, the dependencies of photoacoustic signals amplitude and number on laser pulse energy (5-150 μJ), pulse length (1, 2, 5 ns), and pulse repetition rate (2, 5, 10 kHz) for the melanoma cells were investigated.

In Vivo Laser-Induced Vasoactive Microenvironmental Setting via a Stimuli-Responsive Microstructured Depot.

A stimuli-responsive polymeric three-dimensional microstructured film (PTMF) is a 3D structure with an array of sealed chambers on its external surface. In this work, we demonstrate the use of PTMF as a laser-triggered stimulus-response system for local in vivo targeted blood vessels stimulation by vasoactive substances. The native vascular networks of the mouse mesentery were used as model tissues.

Light distribution in fat cell layers at physiological temperatures.

Adipose tissue (AT) optical properties for physiological temperatures and in vivo conditions are still insufficiently studied. The AT is composed mainly of packed cells close to spherical shape. It is a possible reason that AT demonstrates a very complicated spatial structure of reflected or transmitted light.

Additive Manufacturing of Drug-Eluting Multilayer Biodegradable Films.

Drug-eluting films made of bioresorbable polymers are a widely used tool of modern personalized medicine. However, most currently existing methods of producing coatings do not go beyond the laboratory, as they have low encapsulation efficiency and/or difficulties in scaling up. The PLACE (Printed Layered Adjustable Cargo Encapsulation) technology proposed in this article uses an additive approach for film manufacturing.

Ultrasound-Triggerable Coatings for Foley Catheter Balloons for Local Release of Anti-Inflammatory Drugs during Bladder Neck Dilation.

Bladder neck contracture (BNC) is a complication of the surgical treatment of benign and malignant prostate conditions and is associated with the partial or complete blockage of urination. Correction of this condition usually requires repeated surgical intervention, which does not guarantee recovery. Balloon dilation is a minimally invasive alternative to the surgical dissection of tissues; however, it significantly reduces the patient's quality of life.

Laser Microperforation Assisted Drug-Elution from Biodegradable Films.

In a modern high-tech medicine, drug-eluting polymer coatings are actively used to solve a wide range of problems, including the prevention of post-surgery infection, inflammatory, restenosis, thrombosis and many other implant-associated complications. For major assumptions, the drug elution mechanism is considered mainly to be driven by the degradation of the polymer matrix. This process is very environmentally dependent, unpredictable and often leads to a non-linear drug release kinetic.

Renal Artery Catheterization for Microcapsules' Targeted Delivery to the Mouse Kidney.

The problem of reducing the side effects associated with drug distribution throughout the body in the treatment of various kidney diseases can be solved by effective targeted drug delivery. The method described herein involves injection of a drug encapsulated in polyelectrolyte capsules to achieve prolonged local release and long-term capillary retention of several hours while these capsules are administered via the renal artery. The proposed method does not imply disruption (puncture) of the renal artery or aorta and is suitable for long-term chronic experiments on mice.

Effect of Graphene Oxide and Nanosilica Modifications on Electrospun Core-Shell PVA-PEG-SiO@PVA-GO Fiber Mats.

Electrospinning is a well-established method for the fabrication of polymer biomaterials, including those with core-shell nanofibers. The variability of structures presents a great range of opportunities in tissue engineering and drug delivery by incorporating biologically active molecules such as drugs, proteins, and growth factors and subsequent control of their release into the target microenvironment to achieve therapeutic effect. The object of study is non-woven core-shell PVA-PEG-SiO@PVA-GO fiber mats assembled by the technology of coaxial electrospinning.

"Smart" Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy.

Bacterial infections are a severe medical problem, especially in traumatology, orthopedics, and surgery. The local use of antibiotics-elution materials has made it possible to increase the effectiveness of acute infections treatment. However, the infection prevention problem remains unresolved.

Optical coherence microangiography of the mouse kidney for diagnosis of circulatory disorders.

Optical coherence tomography (OCT) has become widespread in clinical applications in which precise three-dimensional functional imaging of living organs is required. Nevertheless, the kidney is inaccessible for the high resolution OCT imaging due to a high light attenuation coefficient of skin and soft tissues that significantly limits the penetration depth of the probing laser beam. Here, we introduce a surgical protocol and fixation scheme that enables functional visualization of kidney's peritubular capillaries via OCT microangiography.

Lightsheet-based flow cytometer for whole blood with the ability for the magnetic retrieval of objects from the blood flow.

Detection and extraction of circulating tumor cells and other rare objects in the bloodstream are of great interest for modern diagnostics, but devices that can solve this problem for the whole blood volume of laboratory animals are still rare. Here we have developed SPIM-based lightsheet flow cytometer for the detection of fluorescently-labeled objects in whole blood. The bypass channel between two blood vessels connected with the external flow cell was used to visualize, detect, and magnetically separate fluorescently-labeled objects without hydrodynamic focusing.

Effect of Systemic Polyelectrolyte Microcapsule Administration on the Blood Flow Dynamics of Vital Organs.

Polyelectrolyte microcapsules and other targeted drug delivery systems could substantially reduce the side effects of drug and overall toxicity. At the same time, the cardiovascular system is a unique transport avenue that can deliver drug carriers to any tissue and organ. However, one of the most important potential problems of drug carrier systemic administration in clinical practice is that the carriers might cause circulatory disorders, the development of pulmonary embolism, ischemia, and tissue necrosis due to the blockage of small capillaries.

Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety.

Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many of them are lacking effectiveness for kidney targeting, due to systemic dispersion and accumulation in the lungs and liver after intravenous administration. Renal artery administration of carriers provides their effective local accumulation but may cause irreversible vessel blockage.

Photobiomodulation of lymphatic drainage and clearance: perspective strategy for augmentation of meningeal lymphatic functions.

There is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs.

Phenomenon of atypical vascular effects of epinephrine and an increase of photodynamic response by nitroglycerin in rats with colon adenocarcinoma: adrenergic and nitrergic mechanisms and novel applied aspects.

Using an original model of stress-induced colon adenocarcinoma, we uncover atypical vasorelaxation effects of a mucosa injection of epinephrine assessed by laser speckle contrast imaging and a significant increase of fluorescent intensity of 5-ALA/PpIX from malignant colon tissues by a mucosa injection of nitroglycerine. We clearly demonstrate a high activity of adrenergic and nitrergic mechanisms underlying this phenomenon and discuss their application in improving of optical approaches for effective diagnosis of gastrointestinal cancer.

Pilot study of transcranial photobiomodulation of lymphatic clearance of beta-amyloid from the mouse brain: breakthrough strategies for non-pharmacologic therapy of Alzheimer's disease.

In this pilot study, we analyzed effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm) on clearance of beta-amyloid (Aβ) from the mouse brain. The immunohistochemical and confocal data clearly demonstrate the significant reduction of deposition of Aβ plaques in mice after tPBM vs. untreated animals.

Effect of a Controlled Release of Epinephrine Hydrochloride from PLGA Microchamber Array: In Vivo Studies.

This paper presents the synthesis of highly biocompatible and biodegradable poly(lactide- co-glycolide) (PLGA) microchamber arrays sensitive to low-intensity therapeutic ultrasound (1 MHz, 1-2 W, 1 min). A reliable method was elaborated that allowed the microchambers to be uniformly filled with epinephrine hydrochloride (EH), with the possibility of varying the cargo amount. The maximum load of EH was 4.

Photodynamic opening of the blood-brain barrier and pathways of brain clearing.

A new application of the photodynamic treatment (PDT) is presented for the opening of blood-brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous injection of FITC-dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT-related opening of BBB, including clearance from nanoparticles as drug carriers.

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing.

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB.

Off-axis holographic laser speckle contrast imaging of blood vessels in tissues.

Laser speckle contrast imaging (LSCI) has become one of the most common tools for functional imaging in tissues. Incomplete theoretical description and sophisticated interpretation of measurement results are completely sidelined by a low-cost and simple hardware, fastness, consistent results, and repeatability. In addition to the relatively low measuring volume with around 700 ?? ? m of the probing depth for the visible spectral range of illumination, there is no depth selectivity in conventional LSCI configuration; furthermore, in a case of high NA objective, the actual penetration depth of light in tissues is greater than depth of field (DOF) of an imaging system.

Hypoxia and Neonatal Haemorrhagic Stroke: Experimental Study of Mechanisms.

We studied the level of blood oxygen saturation (SpO2) in the brain in newborn rats in the pre- and post-stroke periods, as well as the changes in cerebral blood flow and beta-arrestin-1 as a marker of hypoxic stress. Our results show that mild hypoxia precedes the stroke development and is associated with venous relaxation and decrease blood outflow from the brain resulting in the elevation of synthesis of beta-arrestin-1 in the brain. The incidence of stroke is characterized by severe hypoxia, which is accompanied by the progression of pathological changes in cerebral veins and the high level of beta-arrestin-1.

The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages.

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress.

Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats.

Stress is a major factor for a risk of cerebrovascular catastrophes. Studying of mechanisms underlying stress-related brain-injures in neonates is crucial for development of strategy to prevent of neonatal stroke. Here, using a model of sound-stress-induced intracranial hemorrhages in newborn rats and optical methods, we found that cerebral veins are more sensitive to the deleterious effect of stress than arteries and microvessels.