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Open AccessArticle

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

1
College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea
2
Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea
3
Advanced Analysis Center, Korea Institute of Science and Technology, Hwarang-ro, Seongbuk-gu, Seoul 02792, Korea
4
Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 392; https://doi.org/10.3390/pharmaceutics11080392
Received: 14 June 2019 / Revised: 17 July 2019 / Accepted: 1 August 2019 / Published: 5 August 2019
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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. View Full-Text
Keywords: oxaliplatin; PLGA; hydrogel; intra-abdominal anti-adhesion barrier; colorectal cancer oxaliplatin; PLGA; hydrogel; intra-abdominal anti-adhesion barrier; colorectal cancer
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MDPI and ACS Style

Abuzar, S.M.; Ahn, J.-H.; Park, K.S.; Park, E.J.; Baik, S.H.; Hwang, S.-J. Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment. Pharmaceutics 2019, 11, 392.

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