Effect of Hyaluronic Acid and Pluronic-F68 on the Surface Properties of Foam as a Delivery System for Polidocanol in Sclerotherapy

Castillo-Santaella, Teresa del; Yang, Yan; Martínez-González, Inmaculada; Gálvez-Ruiz, Marı́a José; Cabrerizo-Vílchez, Miguel A.; Holgado-Terriza, Juan A.; Selles-Galiana, Fernando; Maldonado-Valderrama, Julia

doi:10.3390/pharmaceutics12111039

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…For instance, modified foam sclerosants are formed by adding other surfactants to prolong the half-life of the foam. Injectable in situ gels are available to be applied directly at the lesion site to control drugs released locally and avoid many adverse reactions [11,12]. Traditional polymer gels with covalent bonds are commonly used but difficult to degrade in vivo [13].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

et al. 2022

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Venous malformation (VM), which causes severe damage to patients’ appearance and organ function, is one of the most common vascular malformations. At present, many drugs in clinical treatment cause various adverse reactions. Herein, we synthesized cationic amphiphilic gelators (TA6, TA8, and TA9) by introducing saturated carbon chains of different lengths to tranexamic acid (TA), which could self-assemble into low-molecular-weight gels (LMWGs) as drug delivery carriers by hydrogen bonds, van der Waals forces, and hydrophobic interactions. The rheological properties, gelation driving force and drug release profiles of TA6, TA8, and TA9 hydrogels were characterized, and the results indicated that the hydrogels prepared in this study possessed the typical characteristics of a gel and could release drugs slowly. More importantly, the TA9 gelator showed significant pharmacological activity, in that it served as both an active drug compound and a drug carrier. The in vitro experiments demonstrated that TA9 induced HUVECs death and hemolysis by destroying cell membranes in a dose-dependent manner, and caused cell death and hemolysis at a concentration of 0.09 µM/mL. Meanwhile, we found TA9 could interact not only with fibrinogen, but also with other endogenous molecules in the blood. After the administration of TA9 hydrogel for 15 days, macroscopic imaging and histological evaluation in mice and rabbits displayed obvious thrombi, inflammatory reactions, and venous embolization, indicating that the mechanism of the TA9 hydrogel in treating VM was involved in two processes. Firstly, the TA9 hydrogel relied on its mechanical strength to physically block veins and continuously release TA9, in situ, for targeted therapy. Then, TA9 destroyed endothelial cells and damaged venous walls critically, causing thrombi. Most excitingly, TA9 was hydrolyzed to TA by enzymes that inhibited the degradation of thrombi by plasmin to prolong the embolization time and to promote venous fibrosis. Compared with other clinically available sclerosants, the degradation of TA9 also empowered a better biocompatibility and biodegradability for the TA9 hydrogel. In conclusion, we synthesized a potentially safe and effective derivative of TA and developed a low-molecular-weight gel as a self-delivery system for TA in treating VM.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

et al. 2022

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“…The equation predicts a linear relationship between foam stability and viscosity, all other factors being constant. Moreover, a recent study from Castillo 23 indicated that HA increased the surface viscoelasticity of POL, which had a positive impact on the stability of foam. More HA in POL signifies more viscous, cohesive, and stable foam.…”

Section: Discussionmentioning

confidence: 96%

The role of hyaluronic acid in polidocanol foam: An in vitro study

Liu

Xuanxuan

et al. 2022

Phlebology

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Objective To study the role of hyaluronic acid (HA) in polidocanol (POL) foam. Methods The dose-dependent effect of HA-POL on cultured human umbilical vein endothelial cells (HUVECs) as well as foam stability was evaluated by measuring optical density (OD) values and foam half-life time (FHT), respectively. An in vitro model was utilized for estimating the foam blood-displacement capacity by adopting maximum displacement distance (MDD) and displacement time. A comparison of foam viscosity was also carried out. Results The OD values of HUVECs treated with HA first increased and then decreased with the growing dosage of HA while cells treated with HA-POL died. Both FHT and displacement time were prolonged statistically with a gradually enhanced foam viscosity. As to MDD, there were no significant differences. Conclusions HA was found to promote HUVECs proliferation slightly, but this was almost negligible when compared to the cell-killing capacity of 1% POL. The viscosity of POL foam was enhanced by HA indicating its positive correlation with both stability and displacement capacity of POL foam.

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“…One unique application of foam delivery is sclerotherapy. Nonetheless, these sclerotherapeutic injections were performed in a very limited area, and a low volume of foam was applied [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

First In Vivo Applicational Data of Foam-Based Intrathoracic Chemotherapy (FBiTC) in a Swine Model

Khosrawipour,

Nicpoń,

Kiełbowicz

et al. 2023

Pharmaceuticals

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Background: For decades, both intraperitoneal and pleural chemotherapy (IPC) have been delivered as a liquid solution. Recent studies suggest that foam carriers outperform liquid carriers for locoregional chemotherapy. For the first time, this study aims to evaluate the feasibility, safety, and characteristics of foam-based intrathoracic chemotherapy (FBiTC) in an in vivo setting. Methods: In this study, contrast-enhanced FBiTC with doxorubicin was delivered via video-assisted thoracoscopy (VAT) in three swine under general anesthesia. Intraoperative and postoperative parameters, blood analyses, vital signs, and anesthesiologic data were collected. Additionally, an intraoperative computer tomography (CT) scan was performed, and histological tissue sections were collected and further analyzed using fluorescence microscopy. Results: FBiTC was delivered without major complications. End-tidal capnometry detected increased CO2 levels with reduced peripheral oxygen saturation and increased blood pressure and heart rate. No major intra- or postoperative complications were observed. CT scans confirmed a multidirectional distribution pattern of foam. Postoperative laboratory workup did not reveal any critical changes in hemoglobin, white blood count, or platelets. There was no evidence of critical kidney impairment or liver function. Fluorescence microscopy of tissue specimen detected doxorubicin in pleural tissues. Discussion: Our preliminary results are encouraging and indicate that FBiTC is feasible. However, to consider a possible clinical application, further studies are required to investigate the pharmacologic, pharmacodynamic, and physical properties of FBiTC and to ensure the safety of the overall procedure regarding oxygenation levels and capnography parameters.

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Effect of Hyaluronic Acid and Pluronic-F68 on the Surface Properties of Foam as a Delivery System for Polidocanol in Sclerotherapy

Cited by 7 publications

References 47 publications

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

The role of hyaluronic acid in polidocanol foam: An in vitro study

First In Vivo Applicational Data of Foam-Based Intrathoracic Chemotherapy (FBiTC) in a Swine Model

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