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

doi:10.3390/pharmaceutics11080392

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

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

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, AUC_0–48h, C_max, and T_max 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.

Original language	English
Article number	392
Journal	Pharmaceutics
Volume	11
Issue number	8
DOIs	https://doi.org/10.3390/pharmaceutics11080392
Publication status	Published - 2019 Aug

Bibliographical note

Funding Information:
This study was supported by a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea (NRF-2017R1A2B2011520 and NRF-2019R1F1A1056350), and University-Centered Labs-2018R1A6A1A03023718). The authors would like to acknowledge Yonsei Center for Research Facilities (YCRF, Seoul, Korea), Yonsei University for writing assistance.

Funding Information:
Funding: This study was supported by a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea (NRF-2017R1A2B2011520 and NRF-2019R1F1A1056350), and University-Centered Labs-2018R1A6A1A03023718).

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

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Pharmaceutical Science

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@article{1f6956f431a44679996f54c3e6f409a9,

title = "Pharmacokinetic profile and anti-adhesive effect of oxaliplatin-PLGA microparticle-loaded hydrogels in rats for colorectal cancer treatment",

abstract = "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.",

author = "Abuzar, {Sharif Md} and Ahn, {Jun Hyun} and Park, {Kyung Su} and Park, {Eun Jung} and Baik, {Seung Hyuk} and Hwang, {Sung Joo}",

note = "Funding Information: This study was supported by a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea (NRF-2017R1A2B2011520 and NRF-2019R1F1A1056350), and University-Centered Labs-2018R1A6A1A03023718). The authors would like to acknowledge Yonsei Center for Research Facilities (YCRF, Seoul, Korea), Yonsei University for writing assistance. Funding Information: Funding: This study was supported by a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea (NRF-2017R1A2B2011520 and NRF-2019R1F1A1056350), and University-Centered Labs-2018R1A6A1A03023718). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = aug,

doi = "10.3390/pharmaceutics11080392",

language = "English",

volume = "11",

journal = "Pharmaceutics",

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T1 - Pharmacokinetic profile and anti-adhesive effect of oxaliplatin-PLGA microparticle-loaded hydrogels in rats for colorectal cancer treatment

AU - Abuzar, Sharif Md

AU - Ahn, Jun Hyun

AU - Park, Kyung Su

AU - Park, Eun Jung

AU - Baik, Seung Hyuk

AU - Hwang, Sung Joo

N1 - Funding Information: This study was supported by a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea (NRF-2017R1A2B2011520 and NRF-2019R1F1A1056350), and University-Centered Labs-2018R1A6A1A03023718). The authors would like to acknowledge Yonsei Center for Research Facilities (YCRF, Seoul, Korea), Yonsei University for writing assistance. Funding Information: Funding: This study was supported by a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT & Future Planning, Republic of Korea (NRF-2017R1A2B2011520 and NRF-2019R1F1A1056350), and University-Centered Labs-2018R1A6A1A03023718). Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/8

Y1 - 2019/8

N2 - 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.

AB - 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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ER -

Pharmacokinetic profile and anti-adhesive effect of oxaliplatin-PLGA microparticle-loaded hydrogels in rats for colorectal cancer treatment

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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