Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model

Meng Huang Wu, Ming Hung Shih, Wei Bin Hsu, Navneet Kumar Dubey, Wen Fu Lee, Tsai Yu Lin, Meng Yow Hsieh, Chin Fu Chen, Kuo Ti Peng, Tsung Jen Huang, Chung Sheng Shi, Ren Shyang Guo, Chang Jhih Cai, Chiu Yen Chung, Chung Hang Wong

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolacembedded 2, 2′-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Proinflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

Original languageEnglish
Article numbere0186784
JournalPLoS One
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

biodegradability
Hydrogel
hydrocolloids
Postoperative Pain
Rats
pain
animal models
Ketorolac
Sensory Thresholds
Pain Threshold
composite polymers
interleukin-1
Tissue
Interleukin-1
Pain
interleukin-6
Vascular Endothelial Growth Factor A
Sol-gels
Interleukin-6
gels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model. / Wu, Meng Huang; Shih, Ming Hung; Hsu, Wei Bin; Dubey, Navneet Kumar; Lee, Wen Fu; Lin, Tsai Yu; Hsieh, Meng Yow; Chen, Chin Fu; Peng, Kuo Ti; Huang, Tsung Jen; Shi, Chung Sheng; Guo, Ren Shyang; Cai, Chang Jhih; Chung, Chiu Yen; Wong, Chung Hang.

In: PLoS One, Vol. 12, No. 10, e0186784, 01.10.2017.

Research output: Contribution to journalArticle

Wu, MH, Shih, MH, Hsu, WB, Dubey, NK, Lee, WF, Lin, TY, Hsieh, MY, Chen, CF, Peng, KT, Huang, TJ, Shi, CS, Guo, RS, Cai, CJ, Chung, CY & Wong, CH 2017, 'Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model', PLoS One, vol. 12, no. 10, e0186784. https://doi.org/10.1371/journal.pone.0186784
Wu, Meng Huang ; Shih, Ming Hung ; Hsu, Wei Bin ; Dubey, Navneet Kumar ; Lee, Wen Fu ; Lin, Tsai Yu ; Hsieh, Meng Yow ; Chen, Chin Fu ; Peng, Kuo Ti ; Huang, Tsung Jen ; Shi, Chung Sheng ; Guo, Ren Shyang ; Cai, Chang Jhih ; Chung, Chiu Yen ; Wong, Chung Hang. / Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model. In: PLoS One. 2017 ; Vol. 12, No. 10.
@article{dbee3dc26f7a472785d5598d8c92ca09,
title = "Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model",
abstract = "This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolacembedded 2, 2′-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Proinflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt{\%}) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.",
author = "Wu, {Meng Huang} and Shih, {Ming Hung} and Hsu, {Wei Bin} and Dubey, {Navneet Kumar} and Lee, {Wen Fu} and Lin, {Tsai Yu} and Hsieh, {Meng Yow} and Chen, {Chin Fu} and Peng, {Kuo Ti} and Huang, {Tsung Jen} and Shi, {Chung Sheng} and Guo, {Ren Shyang} and Cai, {Chang Jhih} and Chung, {Chiu Yen} and Wong, {Chung Hang}",
year = "2017",
month = "10",
day = "1",
doi = "10.1371/journal.pone.0186784",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model

AU - Wu, Meng Huang

AU - Shih, Ming Hung

AU - Hsu, Wei Bin

AU - Dubey, Navneet Kumar

AU - Lee, Wen Fu

AU - Lin, Tsai Yu

AU - Hsieh, Meng Yow

AU - Chen, Chin Fu

AU - Peng, Kuo Ti

AU - Huang, Tsung Jen

AU - Shi, Chung Sheng

AU - Guo, Ren Shyang

AU - Cai, Chang Jhih

AU - Chung, Chiu Yen

AU - Wong, Chung Hang

PY - 2017/10/1

Y1 - 2017/10/1

N2 - This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolacembedded 2, 2′-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Proinflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

AB - This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolacembedded 2, 2′-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Proinflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

UR - http://www.scopus.com/inward/record.url?scp=85032180177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032180177&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0186784

DO - 10.1371/journal.pone.0186784

M3 - Article

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e0186784

ER -