Abstract
Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations. For the first time, this study investigates the effect of deacetylation degree (DD) of the polysaccharide component in chitosan-g-poly(N-isopropylacrylamide) (CN) carriers on controlled release of pilocarpine in the management of glaucoma. Our results showed that increasing the chitosan DD from 60.7% to 98.5% leads to enhanced biodegradation resistance of carrier and prolonged release profile of the drug. Significant DNA damage and caspase-3 activation could be detected in lens epithelial cell cultures exposed to CN made from highly deacetylated polysaccharides, indicating apoptosis-related cytotoxicity due to relatively high positive charge density of the graft copolymers. Postoperative outcomes demonstrated that long-term therapeutic efficacy in glaucomatous rabbits is governed by intraocular pressure changes in response to intracamerally administered pilocarpine-loaded CN, strongly suggesting the usefulness of deacetylation in this injectable drug delivery carrier.
Original language | English |
---|---|
Pages (from-to) | 375-384 |
Number of pages | 10 |
Journal | Carbohydrate Polymers |
Volume | 197 |
DOIs | |
State | Published - 01 10 2018 |
Bibliographical note
Publisher Copyright:
© 2018 Elsevier Ltd
Keywords
- Biodegradable thermogels
- Chitosan-g-poly(N-isopropylacrylamide)
- Controlled pilocarpine release
- Deacetylation degree
- Injectable drug carrier
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Luo, L. J., Huang, C. C., Chen, H. C., Lai, J. Y., & Matsusaki, M. (2018). Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers. Carbohydrate Polymers, 197, 375-384. https://doi.org/10.1016/j.carbpol.2018.06.020
Luo, Li Jyuan ; Huang, Chih Ching ; Chen, Hung Chi et al. / Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers. In: Carbohydrate Polymers. 2018 ; Vol. 197. pp. 375-384.
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title = "Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers",
abstract = "Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations. For the first time, this study investigates the effect of deacetylation degree (DD) of the polysaccharide component in chitosan-g-poly(N-isopropylacrylamide) (CN) carriers on controlled release of pilocarpine in the management of glaucoma. Our results showed that increasing the chitosan DD from 60.7% to 98.5% leads to enhanced biodegradation resistance of carrier and prolonged release profile of the drug. Significant DNA damage and caspase-3 activation could be detected in lens epithelial cell cultures exposed to CN made from highly deacetylated polysaccharides, indicating apoptosis-related cytotoxicity due to relatively high positive charge density of the graft copolymers. Postoperative outcomes demonstrated that long-term therapeutic efficacy in glaucomatous rabbits is governed by intraocular pressure changes in response to intracamerally administered pilocarpine-loaded CN, strongly suggesting the usefulness of deacetylation in this injectable drug delivery carrier.",
keywords = "Biodegradable thermogels, Chitosan-g-poly(N-isopropylacrylamide), Controlled pilocarpine release, Deacetylation degree, Injectable drug carrier",
author = "Luo, {Li Jyuan} and Huang, {Chih Ching} and Chen, {Hung Chi} and Lai, {Jui Yang} and Michiya Matsusaki",
note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
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doi = "10.1016/j.carbpol.2018.06.020",
language = "英语",
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Luo, LJ, Huang, CC, Chen, HC, Lai, JY & Matsusaki, M 2018, 'Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers', Carbohydrate Polymers, vol. 197, pp. 375-384. https://doi.org/10.1016/j.carbpol.2018.06.020
Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers. / Luo, Li Jyuan; Huang, Chih Ching; Chen, Hung Chi et al.
In: Carbohydrate Polymers, Vol. 197, 01.10.2018, p. 375-384.
Research output: Contribution to journal › Journal Article › peer-review
TY - JOUR
T1 - Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers
AU - Luo, Li Jyuan
AU - Huang, Chih Ching
AU - Chen, Hung Chi
AU - Lai, Jui Yang
AU - Matsusaki, Michiya
N1 - Publisher Copyright:© 2018 Elsevier Ltd
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations. For the first time, this study investigates the effect of deacetylation degree (DD) of the polysaccharide component in chitosan-g-poly(N-isopropylacrylamide) (CN) carriers on controlled release of pilocarpine in the management of glaucoma. Our results showed that increasing the chitosan DD from 60.7% to 98.5% leads to enhanced biodegradation resistance of carrier and prolonged release profile of the drug. Significant DNA damage and caspase-3 activation could be detected in lens epithelial cell cultures exposed to CN made from highly deacetylated polysaccharides, indicating apoptosis-related cytotoxicity due to relatively high positive charge density of the graft copolymers. Postoperative outcomes demonstrated that long-term therapeutic efficacy in glaucomatous rabbits is governed by intraocular pressure changes in response to intracamerally administered pilocarpine-loaded CN, strongly suggesting the usefulness of deacetylation in this injectable drug delivery carrier.
AB - Development of biodegradable thermogels as intracameral injectable carriers for ocular delivery of antiglaucoma medications can provide a better treatment modality with low dosing frequency than eye drop formulations. For the first time, this study investigates the effect of deacetylation degree (DD) of the polysaccharide component in chitosan-g-poly(N-isopropylacrylamide) (CN) carriers on controlled release of pilocarpine in the management of glaucoma. Our results showed that increasing the chitosan DD from 60.7% to 98.5% leads to enhanced biodegradation resistance of carrier and prolonged release profile of the drug. Significant DNA damage and caspase-3 activation could be detected in lens epithelial cell cultures exposed to CN made from highly deacetylated polysaccharides, indicating apoptosis-related cytotoxicity due to relatively high positive charge density of the graft copolymers. Postoperative outcomes demonstrated that long-term therapeutic efficacy in glaucomatous rabbits is governed by intraocular pressure changes in response to intracamerally administered pilocarpine-loaded CN, strongly suggesting the usefulness of deacetylation in this injectable drug delivery carrier.
KW - Biodegradable thermogels
KW - Chitosan-g-poly(N-isopropylacrylamide)
KW - Controlled pilocarpine release
KW - Deacetylation degree
KW - Injectable drug carrier
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DO - 10.1016/j.carbpol.2018.06.020
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SN - 0144-8617
VL - 197
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JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
ER -
Luo LJ, Huang CC, Chen HC, Lai JY, Matsusaki M. Effect of deacetylation degree on controlled pilocarpine release from injectable chitosan-g-poly(N-isopropylacrylamide) carriers. Carbohydrate Polymers. 2018 Oct 1;197:375-384. doi: 10.1016/j.carbpol.2018.06.020