Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor

Lee, Song Yi; Choi, Jin Woo; Lee, Jae Young; Kim, Dae Duk; Kim, Hyo Cheol; Cho, Hyun‐Jong

doi:10.1080/10717544.2018.1480673

Cited by 33 publications

(23 citation statements)

References 41 publications

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“…While non-resorbable beads are currently used for chemoembolization on clinic, resorbable drug-eluting beads gained a lot of focus as they have advantages of transient embolization, not interfering repeat chemoembolization, and complete drug releasing (Marelli et al, 2007;Weng et al, 2011;Choi et al, 2015;Lee et al, 2018). PLGA is a biocompatible and biodegradable polymer and Yang et al used modified PLGA to form ATO-loaded nanoparticles and reached drug load of 10.08%, the highest previously reported value (Yang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal

et al. 2020

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Chemoembolization for hepatocellular carcinoma (HCC) is often suboptimal due to multiple involved signaling and lack of effective drugs. Arsenic trioxide (ATO) is a potent chemotherapeutic agent, which can target multiple signaling and have substantial efficacy on HCC. However, its usage is limited due to systemic toxicity. Using ATO-eluting beads/microspheres for chemoembolization can have locoregional drug delivery and avoid systemic exposure but will require high drug load, which has not been achieved due to low solubility of ATO. Through an innovative approach, we generated the transiently formed ATO microcrystals via micronization and stabilized these microcrystals by solvent exchange. By encapsulating ATO microcrystals, but not individual molecules, with poly(lactide-co-glycolic acid) (PLGA), we developed microspheres cored with extremely high dense ATO. The molar ratio between ATO and PLGA was 157.4:1 and drug load was 40.1%, which is 4–20 fold higher than that of reported ATO nano/microparticles. These microspheres sustainably induced reactive oxygen species, apoptosis, and cytotoxicity on HCC cells and reduced tumor growth by 80% via locoregional delivery. Chemoembolization on mice model showed that ATO-microcrystal loaded microspheres, but not ATO, inhibited HCC growth by 60–75%, which indicates ATO within these microspheres gains the chemoembolizing function via our innovative approach.

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Section: Discussionmentioning

confidence: 99%

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal

et al. 2020

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“…As a typical example, Choi et al (2015) developed DOX embedded PLGA microspheres by the emulsion approach. Furthermore, they further trapped hyaluronic acid-ceramide (HACE) into the PLGA microspheres (MS) during the emulsion process (as shown in Figure 2A), to render TACE reagents with active liver cancer cell targeting ability (Lee et al, 2018). It was worth mentioning that intra-arterial injection of this tumor targeting DOX/HACE MS, with size of 13–44 μm, could significantly inhibit liver tumor growth in a McA-RH7777 liver cancer cell implanted rat tumor model, in comparison with the microspheres without targeting ability (as shown in Figure 2B).…”

Section: Polymer Based Beads or Microparticles As Tace Reagentsmentioning

confidence: 99%

Section: Polymer Based Beads or Microparticles As Tace Reagentsmentioning

confidence: 99%

Recent Advances on Polymeric Beads or Hydrogels as Embolization Agents for Improved Transcatheter Arterial Chemoembolization (TACE)

et al. 2019

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Transcatheter arterial chemoembolization (TACE), aiming to block the hepatic artery for inhibiting tumor blood supply, became a popular therapy for hepatocellular carcinoma (HCC) patients. Traditional TACE formulation of anticancer drug emulsion in ethiodized oil (i.e., Lipiodol ® ) and gelatin sponge (i.e., Gelfoam ® ) had drawbacks on patient tolerance and resulted in undesired systemic toxicity, which were both significantly improved by polymeric beads, microparticles, or hydrogels by taking advantage of the elegant design of biocompatible or biodegradable polymers, especially amphiphilic polymers or polymers with both hydrophilic and hydrophobic chains, which could self-assemble into proposed microspheres or hydrogels. In this review, we aimed to summarize recent advances on polymeric embolization beads or hydrogels as TACE agents, with emphasis on their material basis of polymer architectures, which are important but have not yet been comprehensively summarized.

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“…Sample at each interval has been centrifuged at 1200 rpm for 5 min and the sediment was washed by deionized distilled water then dried at hot air oven overnight at 40°C and exam ined under SEM. 21…”

Section: In Vitro Degradation Studymentioning

confidence: 99%

Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy

2019

J. contemp. med. sci.

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The DRC had been prepared in our laboratory but it required further optimization therefore specific amount of resin (DEAE sephadex A25) was used to prepare a drug:resin ratio (1:8) by suspending the resin in sulfasalazine aqueous solution with at 400 rpm for 120 min at 50°C using hot plate magnetic stirrer then the obtained residue allowed to dry in a hot air oven at 40°C overnight. 9 The drug entrapment efficiency was Objective This work involves preparation and evaluation (in vitro/in vivo) of microcapsules containing sulfasalazine-ion exchange resin complex (resinate) to induce emboli for treatment of solid cancer. Methods The drug-resin complex (resinate) had been optimized by using drug:resin ratio (1:8), by suspending the resin in sulfasalazine aqueous solution with at 400 rpm for 120 min at 50°C. For controlling the release of drug, microencapsulation for the resinate was applied where 21 formulas with different resinate:poly(lactic-co-glycolic acid) ratios 2:1, 1:1 and 1:2 were prepared by solvent evaporation method to study the effect of different variables including resinate:polymer ratio, stirring speed, effect of temperature and aqueous phase volume on microencapsulation efficiency and percent of yield. Results The in vitro release study for the prepared resinate, which had 72% entrapment efficiency, showed 80.992% of drug released within 15 min and the release continued until 99.83% within 75 min formula was found to be F19 had 76.70% encapsulation efficiency and 89.40% yield. The in vitro release study for selected formula showed that 32% of drug released within 1 h and 78% of drug released within 20 days and the release continued up to 96% within 45 days indicating a controlled release manner with spherical microcapsule of 595 µm. The preliminary in vivo work using rabbits showed instant occlusion of the central auricular artery of the rabbit ear leading to ischemia within 3 days that continued to the end of study period. Conclusion This work show the suitability of microcapsules size to prevent blood flow and forming embolization with controlling release of the drug that may treat the solid tumor.

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Hyaluronic acid/doxorubicin nanoassembly-releasing microspheres for the transarterial chemoembolization of a liver tumor

Cited by 33 publications

References 41 publications

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal

Recent Advances on Polymeric Beads or Hydrogels as Embolization Agents for Improved Transcatheter Arterial Chemoembolization (TACE)

Application of PLGA-ion exchange resin microcapsules of sulfasalazine ‎for embolization therapy

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