Journal Article

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

Li, Yi-Chen, Young, Tai-Horng, Hsieh, Hao-Ying, Lee, An Li, Lin, Wei-Yang, Chen, Yi‐Jane, Chen, Ke-Cheng

2020

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aqueous solutions / Biology and Life Sciences / Biomedical engineering / Calorimetry / Cell adhesion & migration / Cell Line / Chemical interactions / Chest / Controlled release / Cytokines / Delayed-Action Preparations - administration & dosage / Deposition / Differential scanning calorimetry / Diseases / Drug Carriers - chemistry / Drug Carriers - toxicity / Drug delivery / Drug delivery systems / Drug Liberation / Drugs / Empyema / Empyema, Pleural - drug therapy / Empyema, Pleural - pathology / Engineering / Engineering and Technology / Extracellular matrix / Extracellular Matrix - drug effects / Extracellular Matrix - metabolism / Fibrin / Fibrin - metabolism / Fibrinolysis / Fibrinolytic Agents - administration & dosage / Fibrinolytic Agents - pharmacokinetics / Fibroblasts / Fibrosis / Fourier transforms / Gels / Humans / Hyaluronic acid / Hyaluronic Acid - chemistry / Hyaluronic Acid - toxicity / Hydrogels / Hydrogels - chemistry / Hydrogels - toxicity / In vitro methods and tests / Infrared spectroscopy / Kinases / Medicine and Health Sciences / Molecular weight / Physical Sciences / Pleural cavity / Pleural effusion / Pneumonia / Poloxamer - chemistry / Poloxamer - toxicity / Poloxamers / Solubility / Spectroscopy / Spectrum analysis / Surgery / Sustained release / Temperature / Thoracic surgery / Thrombolytic drugs / Time / Time Factors / Toxicity / Toxicity testing / Toxicity Tests / U-Plasminogen activator / Urokinase / Urokinase-Type Plasminogen Activator - administration & dosage / Urokinase-Type Plasminogen Activator - pharmacokinetics / Wound drainage