Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept ...termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.
Nitric oxide can activate neutrophils and macrophages, facilitate the synthesis of collagen, which allows significantly accelerating the regeneration of traumatized tissues. We studied the effects of ...nitric oxide-containing gas flow generated by plasma-chemical device "Plason" in a rat model of full-thickness wounds. Histological and morphometric analyses revealed that Plason treated wounds expressed significantly fewer signs of inflammation and contained a more mature granulation tissue on day 4 after the operation. Considering the results of the experimental study, we applied the Plason device in sports medicine for the treatment of lower limb bruises of 34 professional soccer players. Athletes were asked to assess the intensity of pain with the Visual Analogue Scale. Girths of their lower limbs were measured over the course of rehabilitation. Nitric oxide therapy of full-thickness wounds inhibited inflammation and accelerated the regeneration of skin and muscle tissues. Compared with the control, we observed a significant reduction in pain syndrome on days 2-7 after injuries, edema, and hematoma, and shortened treatment duration. This pilot study indicates that the use of nitric oxide is a promising treatment method for sports injuries.
Osteoarthritis (OA) is one of the most common joint diseases worldwide. Unfortunately, clinical methods lack the ability to detect OA in the early stages. Timely detection of the knee joint ...degradation at the level of tissue changes can prevent its progressive damage. Here, diffuse reflectance spectroscopy (DRS) in the NIR range was used to obtain optical markers of the cartilage damage grades and to assess its mechanical properties. It was observed that the water content obtained by DRS strongly correlates with the cartilage thickness (R = .82) and viscoelastic relaxation time (R = .7). Moreover, the spectral parameters, including water content (OH‐band), protein content (CH‐band), and scattering parameters allowed for discrimination between the cartilage damage grades (10−4 < P ≤ 10−3). The developed approach may become a valuable addition to arthroscopy, helping to identify lesions at the microscopic level in the early stages of OA and complement the surgical analysis.
Osteoarthritis (OA) is one of the most common joint diseases worldwide. Methods of early and accurate diagnostics make it possible to provide timely and personalized treatment. Unfortunately, clinical methods lack the ability to detect OA in the early stages. This work is devoted to the development of new approach that may allow rapid detection of early stages of cartilage degradation using diffuse reflectance spectroscopy.
It is known that exogenous nitric oxide (NO) has a bactericidal effect, activates proliferation of fibroblasts, enhances angiogenesis and collagen synthesis, accelerates maturation of granulation ...tissue.
The purpose of this research was to study the dose-dependent therapeutic effect of nitric oxide (NO) in NO-containing gas flows (NO-CGF) applied to the wound surfaces.
The experiment was performed in 36 white Wistar rats with full-thickness skin wounds with an area size of 3 cm2. We used Plason device modified with an experimental plasma-chemical generator of nitric oxide (manipulator) for the following parameters of NO-CGF in the wound surface area: mass flow rate of nitric oxide 2.0 mg/s, axial gas flow velocity 9 m/s, nitric oxide content 1340 ppm, nitrogen dioxide content 108 ppm, gas flow temperature 39°C. Each group included 6 animals. The mass of nitric oxide delivered to the wound varied by the exposure time of 15, 30, 60, 120 and 360 seconds and was 30, 60, 120, 240 and 720 mg, respectively. Wounds were left untreated in the control group. Wound tissues were excised 4 days after the operation and studied with histological, semi-quantitative and morphometric methods.
Histological analysis revealed beneficial effects of NO therapy on wound healing, including reduction of microcirculatory disorders and exudate volume and acceleration of fibroblast proliferation and collagen synthesis. We proved that the most effective stimulation of the wound healing process occurred with a duration of exposure of 120 and 360 seconds (integral mass doses of NO on the wound surfaces were 240 mg and 720 mg, relative mass doses of NO per wound areas were 80 mg/cm2 and 240 mg/cm2, respectively). We did not identify the overdose phenomena after prolonged exposure of the wound to NO.
Our results are important for further improvement of the technique and the standardization of NO-therapy for the treatment of wounds, inflammatory and destructive processes in clinical practice.
Nitric oxide (NO) is a gaseous molecule produced by NO-synthases that regulates a wide range of physiological and pathophysiological processes. Endogenous NO signaling system plays an important role ...in all stages of wound healing. In 1998, a team from Bauman Moscow State Technical University and Sechenov First Moscow State Medical University (Sechenov University) developed the Plason device. Plason generates NO-containing air-plasma flow from atmospheric air and allows to apply required doses of NO to affected areas. It was shown, that exogenous NO penetrates through a wound surface, an intact skin, mucous membranes and a cornea, which leads to the wide range of applications. The experimental and clinical studies of 1992–2006 proved exogenous NO-therapy to be beneficial in patients with extensive purulent wounds, trophic ulcers, diabetic foot syndrome, purulent-inflammatory disease of soft tissues and scars.
Up to now Plason is the only certified in Russia and Europe medical device generating NO from atmospheric air at high therapeutically significant concentrations (500–1200 ppm). It is used in Russia, Ukraine, Belarus and Slovakia. Other air-plasma devices, “Tianox” (Sarov, Russia) and “iNO pulse” (Bellerophon Inc., USA) generated low concentrations of NO (10–100 ppm) were found effective against severe acute respiratory syndrome and recently tested for treatment of COVID-19. The purpose of this review is to acquaint global medical community with the extensive experience of Russian clinicians in NO-therapy. It covers the NO-therapy studies in multiple medical fields published after 2006.
Application of the Plason device was beneficial in treatment of wounds, purulent, traumatic and scar lesions, joint diseases, including sports injuries, as well as in abdominal surgery, dentistry, ophthalmology, otolaryngology and other areas of medicine.
