Hyaluronic acid on the urokinase sustained release with a hydrogel system composed of poloxamer 407: HA/P407 hydrogel system for drug delivery

Abstract

Pleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity. PLOS ONEPLOS ONE | https://doi.org/10., et al. (2020) Hyaluronic acid on the urokinase sustained release with a hydrogel system composed of poloxamer 407: HA/P407 hydrogel system for drug delivery. PLoS ONE 15(3): e0227784. https://doi.org/10.

Icariin-Loaded Hydrogel Regulates Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and Promotes Cartilage Repair in Osteoarthritis

“…Poloxamer 407, a biocompatible polymer, was utilized widely as a thermosensitive material, owing to its performance of rapid thermo-reversible sol–gel transition and the capability to stabilize sustained releasing drugs ( Bai et al, 2020a ; Hsieh et al, 2020 ). Although the surfactant function of Poloxamer 407 is beneficial to the dispersion of drugs in the hydrogels, this capacity may result in the rapid erosion of the hydrogels in several hours under physiological conditions, thus, leading to a burst release of the loaded drugs ( Tundisi et al, 2021 ; Yang et al, 2021 ).…”

“…A simple mixing process is applied to prepare the Poloxamer 407 and HA (PHa) hydrogel in aqueous solution according to previous studies ( Jung et al, 2017 ; Hsieh et al, 2020 ). In brief, Poloxamer 407 (20 wt%) and HA (1 wt%) were dispersed in double distilled water for a further 24 h in a refrigerator at 4°C until a transparent solution was obtained.…”

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders

“…When P407 gel is used alone, it rapidly loses its gelling ability after being diluted in a water-enriched environment. Blending P407 with other polymers such as hyaluronic acid or molecules is a solution to improve drug loading; these composite hydrogels are widely developed in the literature [ 95 , 126 , 127 , 128 ]. For example, P407-based hydrogels are widely used to encapsulate some small molecule drugs, such as ketorolac, metoprolol and doxycycline, which have a molecular weight (MW) of less than 500 Da.…”

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules

“…One of the most commonly used strategies for the formation of physically cross-linked HA hydrogels is the combination of HA with gelling agents, such as poloxamer, ALG, collagen, or more frequently, methylcellulose (MC). , For example, an HA-MC hydrogel was able to sustain the release of IGF-1. The authors modulated the delivery by adding Src homology 3 (SH3)-binding peptides to the polymer chains .…”