Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment
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-(<span style="...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/8/392 |
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| author | Sharif Md Abuzar Jun-Hyun Ahn Kyung Su Park Eun Jung Park Seung Hyuk Baik Sung-Joo Hwang |
| author_facet | Sharif Md Abuzar Jun-Hyun Ahn Kyung Su Park Eun Jung Park Seung Hyuk Baik Sung-Joo Hwang |
| author_sort | Sharif Md Abuzar |
| collection | DOAJ |
| description | 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-(<span style="font-variant: small-caps;">d</span>,<span style="font-variant: small-caps;">l</span>-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, AUC<sub>0−48h</sub>, C<sub>max</sub>, and T<sub>max</sub> 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. |
| first_indexed | 2024-04-11T10:58:55Z |
| format | Article |
| id | doaj.art-ab1b38cef3ab461b88b427db8b4f3aff |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T10:58:55Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ab1b38cef3ab461b88b427db8b4f3aff2022-12-22T04:28:41ZengMDPI AGPharmaceutics1999-49232019-08-0111839210.3390/pharmaceutics11080392pharmaceutics11080392Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer TreatmentSharif Md Abuzar0Jun-Hyun Ahn1Kyung Su Park2Eun Jung Park3Seung Hyuk Baik4Sung-Joo Hwang5College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, KoreaAdvanced Analysis Center, Korea Institute of Science and Technology, Hwarang-ro, Seongbuk-gu, Seoul 02792, KoreaDivision of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaDivision of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaCollege of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, KoreaColorectal 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-(<span style="font-variant: small-caps;">d</span>,<span style="font-variant: small-caps;">l</span>-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, AUC<sub>0−48h</sub>, C<sub>max</sub>, and T<sub>max</sub> 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.https://www.mdpi.com/1999-4923/11/8/392oxaliplatinPLGAhydrogelintra-abdominal anti-adhesion barriercolorectal cancer |
| spellingShingle | Sharif Md Abuzar Jun-Hyun Ahn Kyung Su Park Eun Jung Park Seung Hyuk Baik Sung-Joo Hwang Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment Pharmaceutics oxaliplatin PLGA hydrogel intra-abdominal anti-adhesion barrier colorectal cancer |
| title | Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment |
| title_full | Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment |
| title_fullStr | Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment |
| title_full_unstemmed | Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment |
| title_short | Pharmacokinetic Profile and Anti-Adhesive Effect of Oxaliplatin-PLGA Microparticle-Loaded Hydrogels in Rats for Colorectal Cancer Treatment |
| title_sort | pharmacokinetic profile and anti adhesive effect of oxaliplatin plga microparticle loaded hydrogels in rats for colorectal cancer treatment |
| topic | oxaliplatin PLGA hydrogel intra-abdominal anti-adhesion barrier colorectal cancer |
| url | https://www.mdpi.com/1999-4923/11/8/392 |
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