Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer

Cong-Yu Wang; Min Sun; Zhen Fan; Jian-Zhong Du

doi:10.1007/s10118-022-2726-0

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Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer

RESEARCH ARTICLE | Updated：2022-09-23

- Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer
- Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer
- Chinese Journal of Polymer Science 2022年40卷第10期页码：1154-1164
- Affiliations：
  
  a.Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
  b.Department of Gynaecology and Obstetrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China
- Author bio：
  
  fanzhen2018@tongji.edu.cn (Z.F.)
  jzdu@tongji.edu.cn (J.Z.D.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 22075212 and 21925505), Natural Science Foundation of Shanghai (No. 19ZR1478800), the program for professor of special appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning and Shanghai international scientific collaboration fund (No. 21520710100). J.D. is the recipient of a 5-year National Science Fund for Distinguished Young Scholars.;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-022-2726-0.
- DOI：10.1007/s10118-022-2726-0
  中图分类号：
- 收稿：2022-01-24，
  
  修回：2022-3-20，
  
  录用：2022-3-27，
  
  网络首发：2022-06-24，
  
  纸质出版：2022-10-01
- Accepted：
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Wang, C. Y.; Sun, M.; Fan, Z.; Du, J. Z. Intestine enzyme-responsive polysaccharide-based hydrogel to open epithelial tight junctions for oral delivery of imatinib against colon cancer. Chinese J. Polym. Sci. 2022, 40, 1154–1164

Cong-Yu Wang, Min Sun, Zhen Fan, et al. Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer[J]. Chinese Journal of Polymer Science, 2022, 40(10): 1154-1164.
Wang, C. Y.; Sun, M.; Fan, Z.; Du, J. Z. Intestine enzyme-responsive polysaccharide-based hydrogel to open epithelial tight junctions for oral delivery of imatinib against colon cancer. Chinese J. Polym. Sci. 2022, 40, 1154–1164 DOI： 10.1007/s10118-022-2726-0.

Cong-Yu Wang, Min Sun, Zhen Fan, et al. Intestine Enzyme-responsive Polysaccharide-based Hydrogel to Open Epithelial Tight Junctions for Oral Delivery of Imatinib against Colon Cancer[J]. Chinese Journal of Polymer Science, 2022, 40(10): 1154-1164. DOI： 10.1007/s10118-022-2726-0.

摘要

We developed an intestine enzyme-responsive hydrogel to co-deliver anticancer drug (hydrophobic imatinib) and permeation enhancer (sodium deoxycholate) with long-term controlled release and enhanced intestinal permeability through oral administration (6-fold enhancement of in vivo anticancer effects compared to free imatinib mesylate). This intestine enzyme-responsive hydrogel has great potentials for cancer treatment.

Abstract

Imatinib has been widely used as a selective kinase inhibitor for treating a variety of cancers

and this molecule is very hydrophobic so it is usually modified with mesylate salt in clinic to increase bioavailability. However

pH-dependent aqueous solubility and relatively high dosage of imatinib mesylate greatly reduce the clinical outcomes. To solve this problem

we developed an intestine enzyme-responsive hydrogel to efficiently encapsulate hydrophobic imatinib with long-term controlled release and enhanced intestinal permeability through oral administration. Methacrylic anhydride-modified carboxymethyl chitosan (MA-CMCS) was synthesized

via

amidation reaction and then MA-CMCS was crosslinked with photoinitator under UV-irradation to form a three-dimensional hydrophilic polymer network. The intestine enzyme responsiveness was endowed with imatinib-loaded hydrogel through hydrolyzation of glucosidic bond

which could achieve enzyme-triggered long-term drug release of up to 2 days. Furthermore

sodium deoxycholate was embedded into the hydrogel to synchronously open epithelial tight junctions with improved intestinal permeability.

In vitro

studies revealed similar lethality against colon cancer cell for both imatinib mesylate and imatinib-loaded hydrogels. Moreover

significantly enhanced

in vivo

tumor inhibition (6-fold higher compared to imatinib mesylate) was achieved after oral administration with imatinib-loaded hydrogels. Overall

this enzyme-responsive hydrogel could achieve long-term synchronous release of kinase inhibitor (imatinib) and tight junction permeation enhancer (sodium deoxycholate) at intestine with enhanced therapeutic efficiency

which could provide an effective approach to improve the bioavailability of hydrophobic anticancer chemodrugs with oral administration.

关键词

Keywords

references

Miller, K. D.; Nogueira, L.; Mariotto, A. B.; Rowland, J. H.; Yabroff, K. R.; Alfano, C. M.; Jemal, A.; Kramer, J. L.; Siegel, R. L . Cancer treatment and survivorship statistics, 2019 . CA Cancer J. Clin. , 2019 . 69 363 - 385 . .

Wild, C.; Weiderpass, E.; Stewart, B. W. World cancer report: cancer research for cancer prevention . IARC Press, 2020 .

Khan, F. A.; Albalawi, R.; Pottoo, F. H . Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment . Med. Res. Rev. , 2022 . 42 227 - 258 . DOI: 10.1002/med.21809 http://doi.org/10.1002/med.21809 .

Bukowski, K.; Kciuk, M.; Kontek, R . Mechanisms of multidrug resistance in cancer chemotherapy . Int. J. Mol. Sci. , 2020 . 21,3233 .

Ortiz, R.; Quinonero, F.; Garcia-Pinel, B.; Fuel, M.; Mesas, C.; Cabeza, L.; Melguizo, C.; Prados, J . Nanomedicine to overcome multidrug resistance mechanisms in colon and pancreatic cancer: recent progress . Cancers , 2021 . 13 2058 DOI: 10.3390/cancers13092058 http://doi.org/10.3390/cancers13092058 .

Xie, Y. H.; Chen, Y. X.; Fang, J. Y . Comprehensive review of targeted therapy for colorectal cancer . Sig. Transduct. Target. Ther. , 2020 . 5 22 DOI: 10.1038/s41392-020-0116-z http://doi.org/10.1038/s41392-020-0116-z .

Hammond, W . A.; Swaika, A.; Mody, K. Pharmacologic resistance in colorectal cancer: a review . Ther. Adv. Med. Oncol. , 2016 . 8 57 - 84 . DOI: 10.1177/1758834015614530 http://doi.org/10.1177/1758834015614530 .

Zhang, J.; Yang, P. L.; Gray, N. S . Targeting cancer with small molecule kinase inhibitors . Nat. Rev. Cancer , 2009 . 9 28 - 39 . DOI: 10.1038/nrc2559 http://doi.org/10.1038/nrc2559 .

Baranowska-Kortylewicz, J.; Abe, M.; Pietras, K.; Kortylewicz, Z. P.; Kurizaki, T.; Nearman, J.; Paulsson, J.; Mosley, R. L.; Enke, C. A.; Ostman, A . Effect of platelet-derived growth factor receptor- β inhibition with STI571 on radioimmunotherapy . Cancer Res. , 2005 . 65 7824 - 7831 . DOI: 10.1158/0008-5472.CAN-04-3991 http://doi.org/10.1158/0008-5472.CAN-04-3991 .

Codullo, V.; Cova, E.; Pandolfi, L.; Breda, S.; Morosini, M.; Frangipane, V.; Malatesta, M.; Calderan, L.; Cagnone, M.; Pacini, C.; Cavagna, L.; Recalde, H.; Distler, J. H . W.; Giustra, M.; Prosperi, D.; Colombo, M.; Meloni, F.; Montecucco, C. Imatinib-loaded gold nanoparticles inhibit proliferation of fibroblasts and macrophages from systemic sclerosis patients and ameliorate experimental bleomycin-induced lung fibrosis . J. Control. Release , 2019 . 310 198 - 208 . DOI: 10.1016/j.jconrel.2019.08.015 http://doi.org/10.1016/j.jconrel.2019.08.015 .

El-Mezayen, N. S.; El-Hadidy, W. F.; El-Refaie, W. M.; Shalaby, T. I.; Khattab, M. M.; El-Khatib, A. S . Hepatic stellate cell-targeted imatinib nanomedicine versus conventional imatinib: a novel strategy with potent efficacy in experimental liver fibrosis . J. Control. Release , 2017 . 266 226 - 237 . DOI: 10.1016/j.jconrel.2017.09.035 http://doi.org/10.1016/j.jconrel.2017.09.035 .

Vlahovic, G.; Rabbani, Z. N.; Herndon, J. E., 2nd; Dewhirst, M. W.; Vujaskovic, Z . Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR- β and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation . Br. J. Cancer , 2006 . 95 1013 - 1019 . DOI: 10.1038/sj.bjc.6603366 http://doi.org/10.1038/sj.bjc.6603366 .

Willig, J. B.; Vianna, D. R. B.; Beckenkamp, A.; Beckenkamp, L. R.; Sevigny, J.; Wink, M. R.; Buffon, A.; Pilger, D. A . Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line . Purinergic Signal. , 2020 . 16 29 - 40 . DOI: 10.1007/s11302-019-09686-x http://doi.org/10.1007/s11302-019-09686-x .

Fan, Y.; Du, W.; He, B.; Fu, F.; Yuan, L.; Wu, H.; Dai, W.; Zhang, H.; Wang, X.; Wang, J.; Zhang, X.; Zhang, Q . The reduction of tumor interstitial fluid pressure by liposomal imatinib and its effect on combination therapy with liposomal doxorubicin . Biomaterials , 2013 . 34 2277 - 2288 . DOI: 10.1016/j.biomaterials.2012.12.012 http://doi.org/10.1016/j.biomaterials.2012.12.012 .

Szakács, Z.; Béni, S.; Varga, Z.; Örfi, L.; Kéri, G.; Noszál, B . Acid-base profiling of imatinib (gleevec) and its fragments . J. Med. Chem. , 2005 . 48 249 - 255 . DOI: 10.1021/jm049546c http://doi.org/10.1021/jm049546c .

Nugent, S.; Kumar, D.; Rampton, D.; Evans, D . Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs . Gut , 2001 . 48 571 - 577 . DOI: 10.1136/gut.48.4.571 http://doi.org/10.1136/gut.48.4.571 .

Li, Y.; Yang, B.; Zhang, X . Oral delivery of imatinib through galactosylated polymeric nanoparticles to explore the contribution of a saccharide ligand to absorption . Int. J. Pharm. , 2019 . 568 118508 DOI: 10.1016/j.ijpharm.2019.118508 http://doi.org/10.1016/j.ijpharm.2019.118508 .

Ramazani, F.; Chen, W.; Van Nostrum, C. F.; Storm, G.; Kiessling, F.; Lammers, T.; Hennink, W. E.; Kok, R. J . Formulation and characterization of microspheres loaded with imatinib for sustained delivery . Int. J. Pharm. , 2015 . 482 123 - 130 . DOI: 10.1016/j.ijpharm.2015.01.043 http://doi.org/10.1016/j.ijpharm.2015.01.043 .

Chen, K. H.; Miao, Y. B.; Shang, C. Y.; Huang, T. Y.; Yu, Y. T.; Yeh, C. N.; Song, H. L.; Chen, C. T.; Mi, F. L.; Lin, K. J.; Sung, H. W . A bubble bursting-mediated oral drug delivery system that enables concurrent delivery of lipophilic and hydrophilic chemotherapeutics for treating pancreatic tumors in rats . Biomaterials , 2020 . 255 120157 DOI: 10.1016/j.biomaterials.2020.120157 http://doi.org/10.1016/j.biomaterials.2020.120157 .

O’Brien, S.; Guilhot, F.; Larson, R.; Gathmann, I.; Baccarani, M.; Cervantes, F . The IRIS International study: Imatinib versus interferon and low-dose Ara-C in patients with newly-diagnosed chronic phase chronic myeloid leukemia . New Engl. J. Med. , 2003 . 348 994 - 1004 . DOI: 10.1056/NEJMoa022457 http://doi.org/10.1056/NEJMoa022457 .

Druker, B.; Guilhot, F.; O’Brien, S . Five-year follow-up of imatinib therapy for chronic-phase chronic myeloid leukemia . New Engl. J. Med. , 2006 . 355 2408 - 2417 . DOI: 10.1056/NEJMoa062867 http://doi.org/10.1056/NEJMoa062867 .

Morishima, Y.; Ogura, M.; Nishimura, M.; Yazaki, F.; Bessho, M.; Mizoguchi, H.; Chiba, S.; Hirai, H.; Tauchi, T.; Urabe, A . Efficacy and safety of imatinib mesylate for patients in the first chronic phase of chronic myeloid leukemia: results of a Japanese phase II clinical study . Int. J. Hematol. , 2004 . 80 261 - 266 . DOI: 10.1532/IJH97.04074 http://doi.org/10.1532/IJH97.04074 .

Miyazawa, K.; Nishimaki, J.; Katagiri, T.; Sashida, G.; Shoji, N.; Kawakubo, K.; Suzuki, A.; Shimamoto, T.; Gotoh, A.; Kuriyama, Y . Thrombocytopenia induced by imatinib mesylate (Glivec) in patients with chronic myelogenous leukemia: is 400 mg daily of imatinib mesylate an optimal starting dose for Japanese patients . Int. J. Hematol. , 2003 . 77 93 DOI: 10.1007/BF02982610 http://doi.org/10.1007/BF02982610 .

Carneiro, B. A.; Kaplan, J. B.; Giles, F. J . Tyrosine kinase inhibitor therapy in chronic myeloid leukemia: update on key adverse events . Expert Rev. Hematol. , 2015 . 8 457 - 479 . DOI: 10.1586/17474086.2015.1041910 http://doi.org/10.1586/17474086.2015.1041910 .

Benny, O.; Menon, L. G.; Ariel, G.; Goren, E.; Kim, S. K.; Stewman, C.; Black, P. M.; Carroll, R. S.; Machluf, M . Local delivery of poly lactic-co-glycolic acid microspheres containing imatinib mesylate inhibits intracranial xenograft glioma growth . Clin. Cancer. Res. , 2009 . 15 1222 - 1231 . DOI: 10.1158/1078-0432.CCR-08-1316 http://doi.org/10.1158/1078-0432.CCR-08-1316 .

Gupta, B.; Poudel, B. K.; Tran, T. H.; Pradhan, R.; Cho, H. J.; Jeong, J. H.; Shin, B. S.; Choi, H. G.; Yong, C. S.; Kim, J. O . Modulation of pharmacokinetic and cytotoxicity profile of imatinib base by employing optimized nanostructured lipid carriers . Pharm. Res. , 2015 . 32 2912 - 2927 . DOI: 10.1007/s11095-015-1673-7 http://doi.org/10.1007/s11095-015-1673-7 .

Kimura, S.; Egashira, K.; Nakano, K.; Iwata, E.; Miyagawa, M.; Tsujimoto, H.; Hara, K.; Kawashima, Y.; Tominaga, R.; Sunagawa, K . Local delivery of imatinib mesylate (STI571)-incorporated nanoparticle ex vivo suppresses vein graft neointima formation . Circulation , 2008 . 118 S65 - 70 . .

Palama, I . E.; Cortese, B.; D'Amone, S.; Arcadio, V.; Gigli, G. Coupled delivery of imatinib mesylate and doxorubicin with nanoscaled polymeric vectors for a sustained downregulation of BCR-ABL in chronic myeloid leukemia . Biomater. Sci. , 2015 . 3 361 - 372 . DOI: 10.1039/C4BM00289J http://doi.org/10.1039/C4BM00289J .

Marulanda, K.; Mercel, A.; Gillis, D. C.; Sun, K.; Gambarian, M.; Roark, J.; Weiss, J.; Tsihlis, N. D.; Karver, M. R.; Centeno, S. R.; Peters, E. B.; Clemons, T. D.; Stupp, S. I.; McLean, S. E.; Kibbe, M. R . Intravenous delivery of lung-targeted nanofibers for pulmonary hypertension in mice . Adv. Healthc. Mater. , 2021 . 10 e2100302 DOI: 10.1002/adhm.202100302 http://doi.org/10.1002/adhm.202100302 .

Huang, Y. K.; Tian, H. R.; Zhang, M. Z.; He, J. L.; Liu, J.; Ni, P. H . Monoclonal antibody-conjugated polyphosphoester- hyd -DOX prodrug nanoparticles for targeted chemotherapy of liver cancer cells . Chinese J. Polym. Sci. , 2021 . 39 1392 - 1402 . DOI: 10.1007/s10118-021-2582-3 http://doi.org/10.1007/s10118-021-2582-3 .

Kang, H.; Stiles, W. R.; Baek, Y.; Nomura, S.; Bao, K.; Hu, S.; Park, G. K.; Jo, M. J.; I, H.; Coll, J. L.; Rubin, B. P.; Choi, H. S . Renal clearable theranostic nanoplatforms for gastrointestinal stromal tumors . Adv. Mater. , 2020 . 32 e1905899 DOI: 10.1002/adma.201905899 http://doi.org/10.1002/adma.201905899 .

Brown, T. D.; Whitehead, K. A.; Mitragotri, S . Materials for oral delivery of proteins and peptides . Nat. Rev. Mater. , 2019 . 5 127 - 148 . .

Gong, H. Y.; Chen, Y. G.; Yu, X. S.; Xiao, H.; Xiao, J. P.; Wang, Y.; Shuai, X. T . Co-delivery of doxorubicin and afatinib with pH-responsive polymeric nanovesicle for enhanced lung cancer therapy . Chinese J. Polym. Sci. , 2019 . 37 1224 - 1233 . DOI: 10.1007/s10118-019-2272-6 http://doi.org/10.1007/s10118-019-2272-6 .

Sun, M.; Li, D.; Wang, X.; He, L.; Lv, X.; Xu, Y.; Tang, R . Intestine-penetrating, pH-sensitive and double-layered nanoparticles for oral delivery of doxorubicin with reduced toxicity . J. Mater. Chem. B , 2019 . 7 3692 - 3703 . DOI: 10.1039/C9TB00212J http://doi.org/10.1039/C9TB00212J .

Sun, M.; Hu, H.; Sun, L.; Fan, Z . The application of biomacromolecules to improve oral absorption by enhanced intestinal permeability: a mini-review . Chin. Chem. Lett. , 2020 . 31 1729 - 1736 . DOI: 10.1016/j.cclet.2020.02.035 http://doi.org/10.1016/j.cclet.2020.02.035 .

Peers, S.; Montembault, A.; Ladaviere, C . Chitosan hydrogels for sustained drug delivery . J. Control. Release , 2020 . 326 150 - 163 . DOI: 10.1016/j.jconrel.2020.06.012 http://doi.org/10.1016/j.jconrel.2020.06.012 .

Sakai, M.; Imai, T.; Ohtake, H.; Azuma, H.; Otagiri, M . Simultaneous use of sodium deoxycholate and dipotassium glycyrrhizinate enhances the cellular transport of poorly absorbed compounds across Caco-2 cell monolayers . J. Pharm. Pharmacol. , 1999 . 51 27 - 33 . DOI: doi:10.1211/0022357991772051 http://doi.org/doi:10.1211/0022357991772051 .

Moghimipour, E.; Ameri, A.; Handali, S . Absorption-enhancing effects of bile salts . Molecules , 2015 . 20 14451 - 14473 . DOI: 10.3390/molecules200814451 http://doi.org/10.3390/molecules200814451 .

Alvarez Echazu, M. I.; Olivetti, C. E.; Anesini, C.; Perez, C. J.; Alvarez, G. S.; Desimone, M. F . Development and evaluation of thymol-chitosan hydrogels with antimicrobial-antioxidant activity for oral local delivery . Mater. Sci. Eng. C , 2017 . 81 588 - 596 . DOI: 10.1016/j.msec.2017.08.059 http://doi.org/10.1016/j.msec.2017.08.059 .

Sun, M.; He, L.; Wang, X.; Tang, R . Acid-breakable TPGS-functionalized and diallyl disulfide-crosslinked nanogels for enhanced inhibition of MCF-7/ADR solid tumours . J. Mater. Chem. B , 2019 . 7 240 - 250 . DOI: 10.1039/C8TB02742K http://doi.org/10.1039/C8TB02742K .

Jaiswal, S.; Dutta, P . K.; Kumar, S.; Koh, J.; Pandey, S. Methyl methacrylate modified chitosan: synthesis, characterization and application in drug and gene delivery . Carbohydr. Polym. , 2019 . 211 109 - 117 . DOI: 10.1016/j.carbpol.2019.01.104 http://doi.org/10.1016/j.carbpol.2019.01.104 .

Zha, Q.; Wang, X.; Cheng, X.; Fu, S.; Yang, G.; Yao, W.; Tang, R . Acid-degradable carboxymethyl chitosan nanogels via an ortho ester linkage mediated improved penetration and growth inhibition of 3-D tumor spheroids in vitro . Mater. Sci. Eng. C , 2017 . 78 246 - 257 . DOI: 10.1016/j.msec.2017.04.098 http://doi.org/10.1016/j.msec.2017.04.098 .

Wang, S.; Attah, R.; Li, J.; Chen, Y.; Chen, R . A pH-responsive amphiphilic hydrogel based on pseudopeptides and poly(ethylene glycol) for oral delivery of hydrophobic drugs . ACS Biomater. Sci. Eng. , 2018 . 4 4236 - 4243 . DOI: 10.1021/acsbiomaterials.8b01040 http://doi.org/10.1021/acsbiomaterials.8b01040 .

Ding, Y . F.; Sun, T.; Li, S.; Huang, Q.; Yue, L.; Zhu, L.; Wang, R. Oral colon-targeted konjac glucomannan hydrogel constructed through noncovalent cross-linking by cucurbit[8]uril for ulcerative colitis therapy . ACS Appl. Bio Mater. , 2019 . 3 10 - 19 . .

Meng, F. D.; Ni, Y. X.; Ji, S. F.; Fu, X. H.; Wei, Y. H.; Sun, J.; Li, Z. B . Dual thermal- and pH-responsive polypeptide-based hydrogels . Chinese J. Polym. Sci. , 2017 . 35 1243 - 1252 . DOI: 10.1007/s10118-017-1959-9 http://doi.org/10.1007/s10118-017-1959-9 .

Wang, Y. Q.; Dou, X. Y.; Wang, H. F.; Wang, X.; Wu, D. C . Dendrimer-based hydrogels with controlled drug delivery property for tissue adhesion . Chinese J. Polym. Sci. , 2021 . 39 1421 - 1430 . DOI: 10.1007/s10118-021-2584-1 http://doi.org/10.1007/s10118-021-2584-1 .

Cho, I. S.; Ooya, T . Cell-encapsulating hydrogel puzzle: polyrotaxane-based self-healing hydrogels . Chem. Eur. J. , 2020 . 26 913 - 920 . DOI: 10.1002/chem.201904446 http://doi.org/10.1002/chem.201904446 .

Yin, Y.; Li, X.; Ma, H.; Zhang, J.; Yu, D.; Zhao, R.; Yu, S.; Nie, G.; Wang, H . In situ transforming RNA nanovaccines from polyethylenimine functionalized graphene oxide hydrogel for durable cancer immunotherapy . Nano Lett. , 2021 . 21 2224 - 2231 . DOI: 10.1021/acs.nanolett.0c05039 http://doi.org/10.1021/acs.nanolett.0c05039 .

Tian, R.; Qiu, X.; Yuan, P.; Lei, K.; Wang, L.; Bai, Y.; Liu, S.; Chen, X . Fabrication of self-healing hydrogels with on-demand antimicrobial activity and sustained biomolecule release for infected skin regeneration . ACS Appl. Mater. Interfaces , 2018 . 10 17018 - 17027 . DOI: 10.1021/acsami.8b01740 http://doi.org/10.1021/acsami.8b01740 .

Xiao, Y.; Lu, C.; Liu, Y.; Kong, L.; Bai, H.; Mu, H.; Li, Z.; Geng, H.; Duan, J . Encapsulation of Lactobacillus rhamnosus in hyaluronic acid-based hydrogel for pathogen-targeted delivery to ameliorate enteritis . ACS Appl. Mater. Interfaces , 2020 . 12 36967 - 36977 . DOI: 10.1021/acsami.0c11959 http://doi.org/10.1021/acsami.0c11959 .

Xu, K.; Li, L.; Cui, M.; Han, Y.; Karahan, H. E.; Chow, V. T. K.; Xu, C . Cold chain-free storable hydrogel for infant-friendly Oral delivery of amoxicillin for the treatment of pneumococcal pneumonia . ACS Appl. Mater. Interfaces , 2017 . 9 18440 - 18449 . DOI: 10.1021/acsami.7b01462 http://doi.org/10.1021/acsami.7b01462 .

Xu, X.; Xia, X.; Zhang, K.; Rai, A.; Li, Z.; Zhao, P.; Wei, K.; Zou, L.; Yang, B.; Wong, W. K . Bioadhesive hydrogels demonstrating pH-independent and ultrafast gelation promote gastric ulcer healing in pigs . Sci. Transl. Med. , 2020 . 12 eaba8014 DOI: 10.1126/scitranslmed.aba8014 http://doi.org/10.1126/scitranslmed.aba8014 .

Marslin, G.; Revina, A. M.; Khandelwal, V. K.; Balakumar, K.; Prakash, J.; Franklin, G.; Sheeba, C. J . Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity . Int. J. Nanomedicine , 2015 . 10 3163 - 3170 . .

Roman, D . L.; Roman, M.; Som, C.; Schmutz, M.; Hernandez, E.; Wick, P.; Casalini, T.; Perale, G.; Ostafe, V.; Isvoran, A. Computational assessment of the pharmacological profiles of degradation products of chitosan . Front. Bioeng. Biotech. , 2019 . 7 214 DOI: 10.3389/fbioe.2019.00214 http://doi.org/10.3389/fbioe.2019.00214 .

Fu, D.; Han, B.; Dong, W.; Yang, Z.; Lv, Y.; Liu, W . Effects of carboxymethyl chitosan on the blood system of rats . Biochem. Biophys. Res. Commun. , 2011 . 408 110 - 114 . DOI: 10.1016/j.bbrc.2011.03.130 http://doi.org/10.1016/j.bbrc.2011.03.130 .

Dong, W.; Han, B.; Feng, Y.; Song, F.; Chang, J.; Jiang, H.; Tang, Y.; Liu, W . Pharmacokinetics and biodegradation mechanisms of a versatile carboxymethyl derivative of chitosan in rats: in vivo and in vitro evaluation . Biomacromolecules , 2010 . 11 1527 - 1533 . DOI: 10.1021/bm100158p http://doi.org/10.1021/bm100158p .

Lamson, N. G.; Berger, A.; Fein, K. C.; Whitehead, K. A . Anionic nanoparticles enable the oral delivery of proteins by enhancing intestinal permeability . Nat. Biomed. Eng. , 2020 . 4 84 - 96 . DOI: 10.1038/s41551-019-0465-5 http://doi.org/10.1038/s41551-019-0465-5 .

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