Hyaluronic acid on the urokinase sustained release with a hydrogel system composed of poloxamer 407: HA/P407 hydrogel system for drug delivery
Journal
PLoS ONE
Journal Volume
15
Journal Issue
3
Pages
e0227784
Date Issued
2020
Author(s)
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. ? 2020 Hsieh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
hyaluronic acid; hydrogel; poloxamer; urokinase; drug carrier; fibrin; fibrinolytic agent; hyaluronic acid; poloxamer; urokinase; Article; chemical interaction; controlled study; differential scanning calorimetry; drug cytotoxicity; drug delivery system; drug dosage form comparison; Fourier transform infrared spectroscopy; hydrophilicity; in vitro study; intermethod comparison; loading drug dose; micellization; sustained drug release; administration and dosage; cell line; chemistry; delayed release formulation; drug effect; drug release; extracellular matrix; human; hydrogel; metabolism; pathology; pleura empyema; temperature; time factor; toxicity; toxicity testing; Cell Line; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Empyema, Pleural; Extracellular Matrix; Fibrin; Fibrinolytic Agents; Humans; Hyaluronic Acid; Hydrogels; Poloxamer; Temperature; Time Factors; Toxicity Tests; Urokinase-Type Plasminogen Activator
Publisher
Public Library of Science
Type
journal article