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Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment

 Sharif Md Abuzar  ;  Jun-Hyun Ahn  ;  Kyung Su Park  ;  Eun Jung Park  ;  Seung Hyuk Baik  ;  Sung-Joo Hwang 
 Pharmaceutics, Vol.11(8) : E392, 2019 
Journal Title
Issue Date
PLGA ; colorectal cancer ; hydrogel ; intra-abdominal anti-adhesion barrier ; oxaliplatin
Colorectal cancer (CRC) is one of the most malignant and fatal cancers worldwide. Although cytoreductive surgery combined with chemotherapy is considered a promising therapy, peritoneal adhesion causes further complications after surgery. In this study, oxaliplatin-loaded Poly-(d,l-lactide-co-glycolide) (PLGA) microparticles were prepared using a double emulsion method and loaded into hyaluronic acid (HA)- and carboxymethyl cellulose sodium (CMCNa)-based cross-linked (HC) hydrogels. From characterization and evaluation study PLGA microparticles showed smaller particle size with higher entrapment efficiency, approximately 1100.4 ± 257.7 nm and 77.9 ± 2.8%, respectively. In addition, microparticle-loaded hydrogels showed more sustained drug release compared to the unloaded microparticles. Moreover, in an in vivo pharmacokinetic study after intraperitoneal administration in rats, a significant improvement in the bioavailability and the mean residence time of the microparticle-loaded hydrogels was observed. In HC21 hydrogels, AUC0-48h, Cmax, and Tmax were 16012.12 ± 188.75 ng·h/mL, 528.75 ± 144.50 ng/mL, and 1.5 h, respectively. Furthermore, experimental observation revealed that the hydrogel samples effectively protected injured tissues from peritoneal adhesion. Therefore, the results of the current pharmacokinetic study together with our previous report of the in vivo anti-adhesion efficacy of HC hydrogels demonstrated that the PLGA microparticle-loaded hydrogels offer novel therapeutic strategy for CRC treatment.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Eun Jung(박은정) ORCID logo https://orcid.org/0000-0002-4559-2690
Baik, Seung Hyuk(백승혁) ORCID logo https://orcid.org/0000-0003-4183-2332
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