Hyaluronic Acid Nanoparticles with Parameters Required for In Vivo Applications: From Synthesis to Parametrization.

Hyaluronic acid is an excellent biocompatible material for in vivo applications. Its ability to bind CD44, a cell receptor involved in numerous biological processes, predetermines HA-based nanomaterials as unique carrier for therapeutic and theranostic applications. Although numerous methods for the synthesis of hyaluronic acid nanoparticles (HANPs) are available today, their low reproducibility and wide size distribution hinder the precise assessment of the effect on the organism. A robust and reproducible approach for producing HANPs that meet strict criteria for in vivo applications (e.g., to lung parenchyma) remains challenging. We designed and evaluated four protocols for the preparation of HANPs with those required parameters. The HA molecule was cross-linked by novel combinations of carbodiimide, and four different amine-containing compounds resulted in monodisperse HANPs with a low polydispersity index. By a complex postsynthetic characterization, we confirmed that the prepared HANPs meet the criteria for inhaled therapeutic delivery and other in vivo applications.

Hyaluronic Acid: Known for Almost a Century, but Still in Vogue.

Hyaluronic acid (HA) has a special position among glycosaminoglycans. As a major component of the extracellular matrix (ECM). This simple, unbranched polysaccharide is involved in the regulation of various biological cell processes, whether under physiological conditions or in cases of cell damage. This review summarizes the history of this molecule's study, its distinctive metabolic pathway in the body, its unique properties, and current information regarding its interaction partners. Our main goal, however, is to intensively investigate whether this relatively simple polymer may find applications in protecting against ionizing radiation (IR) or for therapy in cases of radiation-induced damage. After exposure to IR, acute and belated damage develops in each tissue depending upon the dose received and the cellular composition of a given organ. A common feature of all organ damage is a distinct change in composition and structure of the ECM. In particular, the important role of HA was shown in lung tissue and the variability of this flexible molecule in the complex mechanism of radiation-induced lung injuries. Moreover, HA is also involved in intermediating cell behavior during morphogenesis and in tissue repair during inflammation, injury, and would healing. The possibility of using the HA polymer to affect or treat radiation tissue damage may point to the missing gaps in the responsible mechanisms in the onset of this disease. Therefore, in this article, we will also focus on obtaining answers from current knowledge and the results of studies as to whether hyaluronic acid can also find application in radiation science.

Attenuation of Radiation-Induced Lung Injury by Hyaluronic Acid Nanoparticles.

PURPOSE: Therapeutic thorax irradiation as an intervention in lung cancer has its limitations due to toxic effects leading to pneumonitis and/or pulmonary fibrosis. It has already been confirmed that hyaluronic acid (HA), an extracellular matrix glycosaminoglycan, is involved in inflammation disorders and wound healing in lung tissue. We examined the effects after gamma irradiation of hyaluronic acid nanoparticles (HANPs) applied into lung prior to that irradiation in a dose causing radiation-induced pulmonary injuries (RIPI). MATERIALS AND METHODS: Biocompatible HANPs were first used for viability assay conducted on the J774.2 cell line. For in vivo experiments, HANPs were administered intratracheally to C57Bl/6 mice 30 min before thoracic irradiation by 17 Gy. Molecular, cellular, and histopathological parameters were measured in lung and peripheral blood at days 113, 155, and 190, corresponding to periods of significant morphological and/or biochemical alterations of RIPI. RESULTS: Modification of linear hyaluronic acid molecule into nanoparticles structure significantly affected the physiological properties and caused long-term stability against ionizing radiation. The HANPs treatments had significant effects on the expression of the cytokines and particularly on the pro-fibrotic signaling pathway in the lung tissue. The radiation fibrosis phase was altered significantly in comparison with a solely irradiated group. CONCLUSIONS: The present study provides evidence that application of HANPs caused significant changes in molecular and cellular patterns associated with RIPI. These findings suggest that HANPs could diminish detrimental radiation-induced processes in lung tissue, thereby potentially decreasing the extracellular matrix degradation leading to lung fibrosis.