Abstract
Chitooligosaccharides (COS) have been therapeutically effective against a wide range of medical conditions, and the low molecular weight (MW) and, in some cases, a high degree of deacetylation (DD) have enhanced its biological activity. However, these properties can dramatically change the behavior of COS as a drug carrier, especially for drugs that show limited bioavailability. COS-based drug delivery systems (DDS) can be absorbed more readily, and they have faster release characteristics, in addition to exhibiting better biodegradability and bioaccumulation potential. These properties are central to the success of COS in the delivery of a wide variety of drugs, ranging from tumor-targeting drugs to genes. This chapter discusses in depth the impact of MW and DD on COS-based DDS and reviews recent applications.
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Abbreviations
- COS:
-
Chitosan oligomer/chitooligosaccharide
- DDS:
-
Drug delivery systems
- DP:
-
Degree of polymerization
- DD:
-
Degree of deacetylation
- MW:
-
Molecular weight
- TNF-α:
-
Tumor necrosis factor α
- IL-6:
-
Interleukin-6
- iNOS:
-
Inducible nitric oxide synthase
- PI3K/Akt:
-
Phosphatidylinositol 3-kinase-Akt
- VEGF:
-
Vascular endothelial growth factor
- uPA:
-
Urokinase plasminogen activator
- COX-2:
-
Cyclooxygenase
- MCP-1:
-
Monocyte Chemoattractant Protein-1
- TMCO:
-
Trimethylated chitosan oligomer
- EPR:
-
Enhanced permeability and retention
- GP:
-
Glycerolphosphate
- LCST:
-
Lower critical solution temperature
- siRNA:
-
Small interfering ribonucleic acids
- miRNA:
-
Micro RNA mimics
- ASO:
-
Antisense oligonucleotides
- mRNA:
-
Messenger RNA
- NP:
-
Nanoparticles
- PBA:
-
Phenylboronic acid
- PTX:
-
Paclitaxel
- ATRA:
-
All-trans-retinoic acid
- PDLLA:
-
Poly(DL-lactic) acid
- PARP:
-
Poly (ADP-ribose) polymerase
- Bak1:
-
BCL2 Antagonist/Killer 1
- Bax:
-
Bcl-2-associated X protein
- Bcl-2:
-
B-cell lymphoma 2
- PD-L1:
-
Programmed death-ligand 1
- AmB:
-
Amphotericin B
References
Aam BB et al (2010) Production of chitooligosaccharides and their potential applications in medicine. Mar Drugs 8(5):1482–1517. https://doi.org/10.3390/md8051482
Ageitos JM, Chuah J-A, Numata K (2016) Chapter 1 Design considerations for properties of nanocarriers on disposition and efficiency of drug and gene delivery, pp 1–22. https://doi.org/10.1039/9781782622536-00001
Amirani E et al (2020) Effects of chitosan and oligochitosans on the phosphatidylinositol 3-kinase-AKT pathway in cancer therapy. Int J Biol Macromol 164:456–467. https://doi.org/10.1016/j.ijbiomac.2020.07.137
Azuma K et al (2014) Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol 25(10):1935–1940. https://doi.org/10.1093/annonc/mdu242
Barenholz Y (2012) Doxil®—the first FDA-approved nano-drug: lessons learned. J Control Release: off J Control Release Soc 160(2):117–134. https://doi.org/10.1016/j.jconrel.2012.03.020
Berger AG, Chou JJ, Hammond PT (2020) Approaches to modulate the chronic wound environment using localized nucleic acid delivery. Adv Wound Care [Preprint]. https://doi.org/10.1089/wound.2020.1167
Bernkop-Schnürch A, Dünnhaupt S (2012) Chitosan-based drug delivery systems. Eur J Pharm Biopharm 81(3):463–469. https://doi.org/10.1016/j.ejpb.2012.04.007
Bolard J, Joly V, Yeni P (1993) Mechanism of action of amphotericin B at the cellular level. Its modulation by delivery systems. J Liposome Res 3(3):409–427. https://doi.org/10.3109/08982109309150728
Bowe CL et al (1997) Design of compounds that increase the absorption of polar molecules. Proc Natl Acad Sci USA 94(22):12218–12223
Burova TV et al (2020) Biodegradable thermoresponsive oligochitosan nanoparticles: mechanisms of phase transition and drug binding-release. Int J Biol Macromol 164:1451–1460. https://doi.org/10.1016/j.ijbiomac.2020.07.203
Chae SY, Jang M-K, Nah J-W (2005) Influence of molecular weight on oral absorption of water soluble chitosans. J Control Release 102(2):383–394. https://doi.org/10.1016/j.jconrel.2004.10.012
Chandika P et al (2015) Fish collagen/alginate/chitooligosaccharides integrated scaffold for skin tissue regeneration application. Int J Biol Macromol 81:504–513. https://doi.org/10.1016/j.ijbiomac.2015.08.038
Chatterjee S et al (2020) Drug delivery system of dual-responsive PF127 hydrogel with polysaccharide-based nano-conjugate for textile-based transdermal therapy. Carbohydr Polym 236:116074. https://doi.org/10.1016/j.carbpol.2020.116074
Cheng Z et al (2012) Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science (New York, N.Y.) 338(6109):903–910. https://doi.org/10.1126/science.1226338
Cheung RCF et al (2015) Chitosan: an update on potential biomedical and pharmaceutical applications. Mar Drugs 13(8):5156–5186. https://doi.org/10.3390/md13085156
Chung MJ, Park JK, Park YI (2012) Anti-inflammatory effects of low-molecular weight chitosan oligosaccharides in IgE–antigen complex-stimulated RBL-2H3 cells and asthma model mice. Int Immunopharmacol 12(2):453–459. https://doi.org/10.1016/j.intimp.2011.12.027
Contreras-Ruiz L et al (2011) Intracellular trafficking of hyaluronic acid-chitosan oligomer-based nanoparticles in cultured human ocular surface cells. Mol vis 17:279–290
Crouse JZ et al (2015) Development of a microscale red blood cell-shaped pectin-oligochitosan hydrogel system using an electrospray-vibration method: preparation and characterization. J Appl Biomater Funct Mater 13(4):e326-331. https://doi.org/10.5301/jabfm.5000250
De Campos AM et al (2003) The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa. Eur J Pharm Sci off J Eur Feder Pharm Sci 20(1):73–81. https://doi.org/10.1016/s0928-0987(03)00178-7
Dong W et al (2012) Effects of molecular weights on the absorption, distribution and urinary excretion of intraperitoneally administrated carboxymethyl chitosan in rats. J Mater Sci Mater Med 23(12):2945–2952. https://doi.org/10.1007/s10856-012-4747-7
Du Y-Z et al (2010) Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system: Factors affecting the complexation. Int J Pharm 391(1):260–266. https://doi.org/10.1016/j.ijpharm.2010.02.017
Dublin E et al (2000) Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma. Fibroblastic expression has strong associations with tumor pathology. Am J Pathol 157(4):1219–1227. https://doi.org/10.1016/S0002-9440(10)64637-8
Duffy MJ et al (1999) Urokinase plasminogen activator: a prognostic marker in multiple types of cancer. J Surg Oncol 71(2):130–135. https://doi.org/10.1002/(sici)1096-9098(199906)71:2%3c130::aid-jso14%3e3.0.co;2-9
Dyawanapelly S et al (2016) Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins. Drug Deliv Transl Res 6(4):365–379. https://doi.org/10.1007/s13346-016-0295-x
Elbehairi SEI et al (2020) Role of Pd(II)–chitooligosaccharides–Gboxin analog in oxidative phosphorylation inhibition and energy depletion: targeting mitochondrial dynamics. Chem Biol Drug Des 96(4):1148–1161. https://doi.org/10.1111/cbdd.13703
Fenton OS et al (2018) Advances in biomaterials for drug delivery. Adv Mater 30(29):1705328. https://doi.org/10.1002/adma.201705328
Fujita T et al (1994) Control of in vivo fate of albumin derivatives utilizing combined chemical modification. J Drug Target 2(2):157–165. https://doi.org/10.3109/10611869409015905
Garaiova Z et al (2012) Cellular uptake of DNA-chitosan nanoparticles: the role of clathrin- and caveolae-mediated pathways. Int J Biol Macromol 51(5):1043–1051. https://doi.org/10.1016/j.ijbiomac.2012.08.016
Gåserød O, Smidsrød O, Skjåk-Bræk G (1998) Microcapsules of alginate-chitosan—I: A quantitative study of the interaction between alginate and chitosan. Biomaterials 19(20):1815–1825. https://doi.org/10.1016/S0142-9612(98)00073-8
Gelderblom H et al (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer (Oxford, England: 1990) 37(13):1590–1598. https://doi.org/10.1016/s0959-8049(01)00171-x
Genta I, Perugini P, Pavanetto F (1998) Different molecular weight chitosan microspheres: influence on drug loading and drug release. Drug Dev Ind Pharm 24(8):779–784. https://doi.org/10.3109/03639049809082726
Gupta K, Jabrail F (2006) Effects of degree of deacetylation and cross-linking on physical characteristics, swelling and release behavior of chitosan microspheres. Carbohydr Polym 66:43–54. https://doi.org/10.1016/j.carbpol.2006.02.019
Gupta KC, Jabrail F (2007) Glutaraldehyde cross-linked chitosan microspheres for controlled release of centchroman. Carbohydr Res 342:2244–2252. https://doi.org/10.1016/j.carres.2007.06.009
Harish Prashanth KV, Tharanathan RN (2007) Chitin/chitosan: modifications and their unlimited application potential—an overview. Trends Food Sci Technol 18(3):117–131. https://doi.org/10.1016/j.tifs.2006.10.022
Herdiana Y et al (2021) Chitosan-based nanoparticles of targeted drug delivery system in breast cancer treatment. Polymers 13(11):1717. https://doi.org/10.3390/polym13111717
Hou L et al (2012) Pharmacokinetics of a paclitaxel-loaded low molecular weight heparin-all-trans-retinoid acid conjugate ternary nanoparticulate drug delivery system. Biomaterials 33(21):5431–5440. https://doi.org/10.1016/j.biomaterials.2012.03.070
Hou H et al (2016) Chitooligosaccharide inhibits scar formation and enhances functional recovery in a mouse model of sciatic nerve injury. Mol Neurobiol 53(4):2249–2257. https://doi.org/10.1007/s12035-015-9196-0
Hu F-Q et al (2008) Cellular uptake and cytotoxicity of shell crosslinked stearic acid-grafted chitosan oligosaccharide micelles encapsulating doxorubicin. Eur J Pharm Biopharm 69(1):117–125. https://doi.org/10.1016/j.ejpb.2007.09.018
Hu F-Q et al (2009) Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles. Biomaterials 30(36):6955–6963. https://doi.org/10.1016/j.biomaterials.2009.09.008
Hu X et al (2020) Chitooligosaccharides-modified PLGA nanoparticles enhance the antitumor efficacy of AZD9291 (Osimertinib) by promoting apoptosis. Int J Biol Macromol 162:262–272. https://doi.org/10.1016/j.ijbiomac.2020.06.154
Inggrid Setyawati M et al (2015) Understanding and exploiting nanoparticles’ intimacy with the blood vessel and blood. Chem Soc Rev 44(22):8174–8199. https://doi.org/10.1039/C5CS00499C
Issa MM et al (2006) Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo. J Control Release 115(1):103–112. https://doi.org/10.1016/j.jconrel.2006.06.029
Jafari H et al (2020) Chitooligosaccharides for wound healing biomaterials engineering. Mater Sci Eng C Mater Biol Appl 117:111266. https://doi.org/10.1016/j.msec.2020.111266
Jiang C et al (2014) Deoxycholic acid-modified chitooligosaccharide/mPEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy. Int J Pharm 475(1–2):60–68. https://doi.org/10.1016/j.ijpharm.2014.08.037
Jiang Z et al (2021) Effect of chitosan oligosaccharide-conjugated selenium on improving immune function and blocking gastric cancer growth. Eur J Pharmacol 891:173673. https://doi.org/10.1016/j.ejphar.2020.173673
Kanasty R et al (2013) Delivery materials for siRNA therapeutics. Nat Mater 12(11):967–977. https://doi.org/10.1038/nmat3765
Karmakar S, Banik NL, Ray SK (2008) Combination of all-trans retinoic acid and paclitaxel-induced differentiation and apoptosis in human glioblastoma U87MG xenografts in nude mice. Cancer 112(3):596–607. https://doi.org/10.1002/cncr.23223
Kim CJ (1998) Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets. Drug Dev Ind Pharm 24(7):645–651. https://doi.org/10.3109/03639049809082366
Kim M-O et al (2013) Water-soluble chitosan sensitizes apoptosis in human leukemia cells via the downregulation of Bcl-2 and dephosphorylation of akt. J Food Biochem 37(3):270–277. https://doi.org/10.1111/j.1745-4514.2011.00628.x
Klausner EA et al (2010) Ultrapure chitosan oligomers as carriers for corneal gene transfer. Biomaterials 31(7):1814–1820. https://doi.org/10.1016/j.biomaterials.2009.10.031
Klokkevold PR et al (1999) The effect of chitosan (poly-N-acetyl glucosamine) on lingual hemostasis in heparinized rabbits. J Oral Maxillofac Surg 57(1):49–52. https://doi.org/10.1016/S0278-2391(99)90632-8
Ko YG et al (2011) Gelation of chitin and chitosan dispersed suspensions under electric field: effect of degree of deacetylation. ACS Appl Mater Interfaces 3(4):1289–1298. https://doi.org/10.1021/am200091r
Koo H et al (2013) Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery. J Control Release: off J Control Release Soc 172(3):823–831. https://doi.org/10.1016/j.jconrel.2013.08.297
Köping-Höggård M et al (2001) Chitosan as a nonviral gene delivery system. Structure–property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo. Gene Ther 8(14):1108–1121. https://doi.org/10.1038/sj.gt.3301492
Koutsilieri E, Rethwilm A, Scheller C (2007) The therapeutic potential of siRNA in gene therapy of neurodegenerative disorders. J Neural Transm Suppl 72:43–49. https://doi.org/10.1007/978-3-211-73574-9_7
Kr S, N S, Jm M (2000) Raloxifene hydrochloride. Am J Health-Syst Pharm: AJHP: Off J Am Soc Health-Syst Pharm 57(18). https://pubmed.ncbi.nlm.nih.gov/11006795/. Accessed 25 July 2021
Kristiansen A, Vårum KM, Grasdalen H (1998) The interactions between highly de-N-acetylated chitosans and lysozyme from chicken egg white studied by 1H-NMR spectroscopy. Eur J Biochem 251(1–2):335–342. https://doi.org/10.1046/j.1432-1327.1998.2510335.x
Kumari M, Liu C-H, Wu W-C (2020) Oligochitosan modified albumin as plasmid DNA delivery vector: endocytic trafficking, polyplex fate, in vivo compatibility. Int J Biol Macromol 142:492–502. https://doi.org/10.1016/j.ijbiomac.2019.09.121
Lai M-Y et al (2003) Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats. J Pharm Pharmacol 55(2):205–209. https://doi.org/10.1211/002235702522
Lee DW et al (2003) Effect of gamma-irradiation on degradation of alginate. J Agric Food Chem 51(16):4819–4823. https://doi.org/10.1021/jf021053y
Lee JH, Yeo Y (2015) Controlled drug release from pharmaceutical nanocarriers. Chem Eng Sci 125:75–84. https://doi.org/10.1016/j.ces.2014.08.046
Li J et al (2016) A comparative study on the efficiency of chitosan-N-acetylcysteine, chitosan oligosaccharides or carboxymethyl chitosan surface modified nanostructured lipid carrier for ophthalmic delivery of curcumin. Carbohydr Polym 146:435–444. https://doi.org/10.1016/j.carbpol.2016.03.079
Lieberman J (2018) Tapping the RNA world for therapeutics. Nat Struct Mol Biol 25(5):357–364. https://doi.org/10.1038/s41594-018-0054-4
Liu W et al (2011) Tumor-derived vascular endothelial growth factor (VEGF)-a facilitates tumor metastasis through the VEGF-VEGFR1 signaling pathway. Int J Oncol 39(5):1213–1220. https://doi.org/10.3892/ijo.2011.1138
Liu S-H, Chen F-W, Chiang M-T (2021a) Chitosan oligosaccharide alleviates abnormal glucose metabolism without inhibition of hepatic lipid accumulation in a high-fat diet/streptozotocin-induced diabetic rat model. Mar Drugs 19(7):360. https://doi.org/10.3390/md19070360
Liu X et al (2021b) Enhancing anti-melanoma outcomes in mice using novel chitooligosaccharide nanoparticles loaded with therapeutic survivin-targeted siRNA. Eur J Pharm Sci 158:105641. https://doi.org/10.1016/j.ejps.2020.105641
Lopes JR et al (2013) Physical and chemical stimuli-responsive drug delivery systems: targeted delivery and main routes of administration. Curr Pharm Des 19(41):7169–7184. https://doi.org/10.2174/13816128113199990698
Lozano MV et al (2008) Highly efficient system to deliver taxanes into tumor cells: docetaxel-loaded chitosan oligomer colloidal carriers. Biomacromol 9(8):2186–2193. https://doi.org/10.1021/bm800298u
Maganti N et al (2011) Structure-process-property relationship of biomimetic chitosan-based nanocomposite scaffolds for tissue engineering: biological, physico-chemical, and mechanical functions. Adv Eng Mater 13(3):B108–B122. https://doi.org/10.1002/adem.201080094
Mahmoodi Chalbatani G et al (2019) Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach. Int J Nanomed 14:3111–3128. https://doi.org/10.2147/IJN.S200253
Mallakuntla MK et al (2021) Chitooligosaccharides induce apoptosis in human breast cancer cells. Carbohydr Polym Technol Appl 2:100077. https://doi.org/10.1016/j.carpta.2021.100077
Manzari MT et al (2021) Targeted drug delivery strategies for precision medicines. Nat Rev Mater 6(4):351–370. https://doi.org/10.1038/s41578-020-00269-6
Mei Y et al (2013) Protective effect of chitooligosaccharides against cyclophosphamide-induced immunosuppression in mice. Int J Biol Macromol 62:330–335. https://doi.org/10.1016/j.ijbiomac.2013.09.038
Mendis E et al (2007) An in vitro cellular analysis of the radical scavenging efficacy of chitooligosaccharides. Life Sci 80(23):2118–2127. https://doi.org/10.1016/j.lfs.2007.03.016
Mengíbar M et al (2013) Influence of the physico-chemical characteristics of chito-oligosaccharides (COS) on antioxidant activity. Carbohydr Polym 97(2):776–782. https://doi.org/10.1016/j.carbpol.2013.05.035
Mizuno K et al (2008) Pretreatment with low doses of erythropoietin ameliorates brain damage in periventricular leukomalacia by targeting late oligodendrocyte progenitors: a rat model. Neonatology 94(4):255–266. https://doi.org/10.1159/000151644
Moorthy MS et al (2019) Chitosan oligosaccharide coated mesoporous silica nanoparticles for pH-stimuli responsive drug delivery applications. J Porous Mater 26(1):217–226. https://doi.org/10.1007/s10934-018-0646-8
Morales JO et al (2017) Challenges and future prospects for the delivery of biologics: oral mucosal, pulmonary, and transdermal routes. AAPS J 19(3):652–668. https://doi.org/10.1208/s12248-017-0054-z
Muanprasat C, Chatsudthipong V (2017) Chitosan oligosaccharide: biological activities and potential therapeutic applications. Pharmacol Ther 170:80–97. https://doi.org/10.1016/j.pharmthera.2016.10.013
Naqvi S, Moerschbacher BM (2017) The cell factory approach toward biotechnological production of high-value chitosan oligomers and their derivatives: an update. Crit Rev Biotechnol 37(1):11–25. https://doi.org/10.3109/07388551.2015.1104289
Naveed M et al (2019) Chitosan oligosaccharide (COS): an overview. Int J Biol Macromol 129:827–843. https://doi.org/10.1016/j.ijbiomac.2019.01.192
Nguyen M-H, Lee SE et al (2019a) A simple strategy to enhance the in vivo wound-healing activity of curcumin in the form of self-assembled nanoparticle complex of curcumin and oligochitosan. Mater Sci Eng C Mater Biol Appl 98:54–64. https://doi.org/10.1016/j.msec.2018.12.091
Nguyen M-H, Vu N-B-D et al (2019b) In vivo comparison of wound healing and scar treatment effect between curcumin-oligochitosan nanoparticle complex and oligochitosan-coated curcumin-loaded-liposome. J Microencapsul 36(2):156–168. https://doi.org/10.1080/02652048.2019.1612476
Nishikawa M et al (1992) Pharmacokinetics of receptor-mediated hepatic uptake of glycosylated albumin in mice. Int J Pharm 85(1):75–85. https://doi.org/10.1016/0378-5173(92)90136-P
Oh G-W et al (2021) Characterization of an oxidized alginate-gelatin hydrogel incorporating a COS-salicylic acid conjugate for wound healing. Carbohydr Polym 252:117145. https://doi.org/10.1016/j.carbpol.2020.117145
Okamoto Y et al (2003) Effects of chitin and chitosan on blood coagulation. Carbohyd Polym 53(3):337–342. https://doi.org/10.1016/S0144-8617(03)00076-6
Onishi H, Machida Y (1999) Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials 20(2):175–182. https://doi.org/10.1016/S0142-9612(98)00159-8
Parachoniak CA, Park M (2012) Dynamics of receptor trafficking in tumorigenicity. Trends Cell Biol 22(5):231–240. https://doi.org/10.1016/j.tcb.2012.02.002
Parhi R (2020) Drug delivery applications of chitin and chitosan: a review. Environ Chem Lett 18(3):577–594. https://doi.org/10.1007/s10311-020-00963-5
Park E-J et al (2012) Doxorubicin induces cytotoxicity through upregulation of pERK–dependent ATF3. PLoS ONE 7(9):e44990. https://doi.org/10.1371/journal.pone.0044990
Park H-H et al (2018) Characterization and biological activity of PVA hydrogel containing chitooligosaccharides conjugated with gallic acid. Carbohydr Polym 198:197–205. https://doi.org/10.1016/j.carbpol.2018.06.070
Park P-J, Je J-Y, Kim S-K (2003) Free radical scavenging activity of chitooligosaccharides by electron spin resonance spectrometry. J Agric Food Chem 51(16):4624–4627. https://doi.org/10.1021/jf034039+
Peppas NA, Reinhart CT (1983) Solute diffusion in swollen membranes. Part I. A new theory. J Membr Sci 15(3):275–287. https://doi.org/10.1016/S0376-7388(00)82304-2
Qiu F, He Z-G, Li H-Z (2003) HPLC analyses and pharmacokinetic studies of baicalin and oxymatrine in rabbits. Pharmazie 58(9):616–619
Rehmann MS et al (2017) Tuning and predicting mesh size and protein release from step growth hydrogels. Biomacromol 18(10):3131–3142. https://doi.org/10.1021/acs.biomac.7b00781
Richardson SC, Kolbe HV, Duncan R (1999) Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA. Int J Pharm 178(2):231–243. https://doi.org/10.1016/s0378-5173(98)00378-0
Rosenblum D et al (2018) Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun 9(1):1410. https://doi.org/10.1038/s41467-018-03705-y
Sacco P et al (2018) The role played by the molecular weight and acetylation degree in modulating the stiffness and elasticity of chitosan gels. Carbohyd Polym 196:405–413. https://doi.org/10.1016/j.carbpol.2018.05.060
Salah R et al (2013) Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1. Int J Biol Macromol 52:333–339. https://doi.org/10.1016/j.ijbiomac.2012.10.009
Sandri G et al (2012) The role of chitosan as a mucoadhesive agent in mucosal drug delivery. J Drug Deliv Sci Technol 22(4):275–284. https://doi.org/10.1016/S1773-2247(12)50046-8
Sandri G et al (2017) Halloysite and chitosan oligosaccharide nanocomposite for wound healing. Acta Biomater 57:216–224. https://doi.org/10.1016/j.actbio.2017.05.032
Saravanakumar G et al (2009) Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: synthesis, characterization, and in vivo biodistribution. J Control Release: off J Control Release Soc 140(3):210–217. https://doi.org/10.1016/j.jconrel.2009.06.015
Schipper NG et al (1997) Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement. Pharm Res 14(7):923–929. https://doi.org/10.1023/a:1012160102740
Schipper NG, Vårum KM, Artursson P (1996) Chitosans as absorption enhancers for poorly absorbable drugs. 1: influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial (Caco-2) cells. Pharm Res 13(11):1686–1692. https://doi.org/10.1023/a:1016444808000
Seong JS, Yun ME, Park SN (2018) Surfactant-stable and pH-sensitive liposomes coated with N-succinyl-chitosan and chitooligosaccharide for delivery of quercetin. Carbohydr Polym 181:659–667. https://doi.org/10.1016/j.carbpol.2017.11.098
Shahbazi B et al (2015) Preparation and characterization of silk fibroin/oligochitosan nanoparticles for siRNA delivery. Colloids Surf B Biointerfaces 136:867–877. https://doi.org/10.1016/j.colsurfb.2015.10.044
Shaikh R et al (2011) Mucoadhesive drug delivery systems. J Pharm Bioallied Sci 3(1):89–100. https://doi.org/10.4103/0975-7406.76478
Shao K et al (2015) Pharmacokinetics and biodegradation performance of a hydroxypropyl chitosan derivative. J Ocean Univ China 14(5):888–896. https://doi.org/10.1007/s11802-015-2600-6
Song Z et al (2018) Oligochitosan-pluronic 127 conjugate for delivery of honokiol. Artif Cells Nanomed Biotechnol 46(sup1):740–750. https://doi.org/10.1080/21691401.2018.1434785
Song Z et al (2019) Linolenic acid-modified methoxy poly (ethylene glycol)-oligochitosan conjugate micelles for encapsulation of amphotericin B. Carbohydr Polym 205:571–580. https://doi.org/10.1016/j.carbpol.2018.10.086
Sparreboom A et al (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci 94(5):2031–2035. https://doi.org/10.1073/pnas.94.5.2031
Srinivasarao M, Low PS (2017) Ligand-targeted drug delivery. Chem Rev 117(19):12133–12164. https://doi.org/10.1021/acs.chemrev.7b00013
Stealey S et al (2020) Calcium-oligochitosan-pectin microcarrier for colonic drug delivery. Pharm Dev Technol 25(2):260–265. https://doi.org/10.1080/10837450.2019.1691591
Sutthasupha P, Lungkaphin A (2020) The potential roles of chitosan oligosaccharide in prevention of kidney injury in obese and diabetic conditions. Food Funct 11(9):7371–7388. https://doi.org/10.1039/d0fo00302f
Svenson S (2004) Carrier-based drug delivery. In: Carrier-based drug delivery. American Chemical Society (ACS Symposium Series, vol 879), pp 2–23. https://doi.org/10.1021/bk-2004-0879.ch001.
Tabassum N, Ahmed S, Ali MA (2021) Chitooligosaccharides and their structural-functional effect on hydrogels: a review. Carbohydr Polym 261:117882. https://doi.org/10.1016/j.carbpol.2021.117882
Tang Q et al (2019) A pH-responsive self-healing hydrogel based on multivalent coordination of Ni2+ with polyhistidine-terminated PEG and IDA-modified oligochitosan. J Mater Chem B 7(1):30–42. https://doi.org/10.1039/c8tb02360c
Thanou M, Verhoef JC, Junginger HE (2001) Chitosan and its derivatives as intestinal absorption enhancers. Adv Drug Deliv Rev 50(Suppl 1):S91-101. https://doi.org/10.1016/s0169-409x(01)00180-6
Thanou M et al (2002) Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials 23(1):153–159. https://doi.org/10.1016/s0142-9612(01)00090-4
Trzciński S (2006) 13. Combined degradation of chitosans, p 9
Vo T-S, Kong C-S, Kim S-K (2011) Inhibitory effects of chitooligosaccharides on degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. Carbohydr Polym 84(1):649–655. https://doi.org/10.1016/j.carbpol.2010.12.046
Wang Z, Li Y (2018) Raloxifene/SBE-β-CD inclusion complexes formulated into nanoparticles with chitosan to overcome the absorption barrier for bioavailability enhancement. Pharmaceutics 10(3):E76. https://doi.org/10.3390/pharmaceutics10030076
Wang T et al (2012) Erythropoietin-loaded oligochitosan nanoparticles for treatment of periventricular leukomalacia. Int J Pharm 422(1–2):462–471. https://doi.org/10.1016/j.ijpharm.2011.10.058
Wang Y et al (2016) Biodegradable functional polycarbonate micelles for controlled release of amphotericin B. Acta Biomater 46:211–220. https://doi.org/10.1016/j.actbio.2016.09.036
Wang K et al (2018) Nanoceria-loaded injectable hydrogels for potential age-related macular degeneration treatment. J Biomed Mater Res Part A 106(11):2795–2804. https://doi.org/10.1002/jbm.a.36450
Whitehead KA et al (2011) Silencing or stimulation? siRNA delivery and the immune system. Annu Rev Chem Biomol Eng 2:77–96. https://doi.org/10.1146/annurev-chembioeng-061010-114133
Wong K et al (2006) PEI-g-chitosan, a novel gene delivery system with transfection efficiency comparable to polyethylenimine in vitro and after liver administration in vivo. Bioconjug Chem 17(1):152–158. https://doi.org/10.1021/bc0501597
Wu Y et al (2008) Coagulation property of hyaluronic acid–collagen/chitosan complex film. J Mater Sci Mater Med 19(12):3621–3629. https://doi.org/10.1007/s10856-008-3477-3
Wu H et al (2012) Inhibition of angiogenesis by chitooligosaccharides with specific degrees of acetylation and polymerization. Carbohydr Polym 89(2):511–518. https://doi.org/10.1016/j.carbpol.2012.03.037
Wu N et al (2015) Immunostimulative activity of low molecular weight chitosans in RAW264.7 macrophages. Mar Drugs 13(10):6210–6225. https://doi.org/10.3390/md13106210
Xin C et al (2018) Stearic acid-grafted chitooligosaccharide nanomicelle system with biocleavable gadolinium chelates as a multifunctional agent for tumor imaging and drug delivery. Pharm Res 36(1):10. https://doi.org/10.1007/s11095-018-2530-2
Xing R et al (2017) Monomer composition of chitooligosaccharides obtained by different degradation methods and their effects on immunomodulatory activities. Carbohydr Polym 157:1288–1297. https://doi.org/10.1016/j.carbpol.2016.11.001
Xing P, Zhao Y (2018) Supramolecular vesicles for stimulus-responsive drug delivery. Small Methods 2(4):1700364. https://doi.org/10.1002/smtd.201700364
Xiong C et al (2009) Potent angiogenic inhibition effects of deacetylated chitohexaose separated from chitooligosaccharides and its mechanism of action in vitro. Carbohydr Res 344(15):1975–1983. https://doi.org/10.1016/j.carres.2009.06.036
Yamada K et al (2005) Chitosan oligomers as potential and safe absorption enhancers for improving the pulmonary absorption of interferon-alpha in rats. J Pharm Sci 94(11):2432–2440. https://doi.org/10.1002/jps.20454
Yang H-C, Hon M-H (2009) The effect of the molecular weight of chitosan nanoparticles and its application on drug delivery. Microchem J 92(1):87–91. https://doi.org/10.1016/j.microc.2009.02.001
Yang H-C, Hon M-H (2010) The effect of the degree of deacetylation of chitosan nanoparticles and its characterization and encapsulation efficiency on drug delivery. Polym-Plast Technol Eng 49(12):1292–1296. https://doi.org/10.1080/03602559.2010.482076
Yhee JY et al (2013) The EPR effect in cancer therapy. In: Bae YH, Mrsny RJ, Park K (eds) Cancer targeted drug delivery: an elusive dream. Springer, New York, NY, pp 621–632. https://doi.org/10.1007/978-1-4614-7876-8_23
Yin X et al (2017) Chitooligosaccharides modified reduction-sensitive liposomes: enhanced cytoplasmic drug delivery and osteosarcomas-tumor inhibition in animal models. Pharm Res 34(10):2172–2184. https://doi.org/10.1007/s11095-017-2225-0
Yin X et al (2018) Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma. Drug Deliv 25(1):900–908. https://doi.org/10.1080/10717544.2018.1458920
Yomota C, Komuro T, Kimura T (1990) Studies on the degradation of chitosan films by lysozyme and release of loaded chemicals. Yakugaku Zasshi: J Pharm Soc Jpn 110(6):442–448. https://doi.org/10.1248/yakushi1947.110.6_442
Yousef M et al (2012) Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: therapeutic efficacy and possible mechanisms of action. Pharmacol Res 66(1):66–79. https://doi.org/10.1016/j.phrs.2012.03.013
Yu S-Y et al (2017) Antidiabetic effect of chitosan oligosaccharide (GO2KA1) is mediated via inhibition of intestinal alpha-glucosidase and glucose transporters and PPARγ expression. BioFactors 43(1):90–99. https://doi.org/10.1002/biof.1311
Yuan Z et al (2011) Enhanced accumulation of low-molecular-weight chitosan in kidneys: a study on the influence of N-acetylation of chitosan on the renal targeting. J Drug Target 19(7):540–551. https://doi.org/10.3109/1061186X.2010.521158
Yue Z-G et al (2011) Surface charge affects cellular uptake and intracellular trafficking of chitosan-based nanoparticles. Biomacromol 12(7):2440–2446. https://doi.org/10.1021/bm101482r
Zaghloul N, Patel H, Ahmed MN (2017) A model of Periventricular Leukomalacia (PVL) in neonate mice with histopathological and neurodevelopmental outcomes mimicking human PVL in neonates. PLoS ONE 12(4):e0175438. https://doi.org/10.1371/journal.pone.0175438
Zeng L et al (2008) Absorption and distribution of chitosan in mice after oral administration. Carbohydr Polym 71(3):435–440. https://doi.org/10.1016/j.carbpol.2007.06.016
Zhang J et al (2010) Chitosan modification and pharmaceutical/biomedical applications. Mar Drugs 8(7):1962–1987. https://doi.org/10.3390/md8071962
Zhang J et al (2015) Polymeric nanoparticles based on chitooligosaccharide as drug carriers for co-delivery of all-trans-retinoic acid and paclitaxel. Carbohydr Polym 129:25–34. https://doi.org/10.1016/j.carbpol.2015.04.036
Zhang W et al (2016) Novel pectin-based carriers for colonic drug delivery. Pharm Dev Technol 21(1):127–130. https://doi.org/10.3109/10837450.2014.965327
Zhang J et al (2020) Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion. J Zhejiang Univ Sci B 21(8):611–627. https://doi.org/10.1631/jzus.B2000172
Zhao Y et al (2018) Chitosan oligosaccharides alleviate PM2.5-induced lung inflammation in rats. Environ Sci Pollut Res 25. https://doi.org/10.1007/s11356-018-3365-4
Zheng F et al (2007) Chitosan nanoparticle as gene therapy vector via gastrointestinal mucosa administration: results of an in vitro and in vivo study. Life Sci 80(4):388–396. https://doi.org/10.1016/j.lfs.2006.09.040
Zheng B et al (2016) Molecular weight-dependent immunostimulative activity of low molecular weight chitosan via regulating NF-κB and AP-1 signaling pathways in RAW264.7 macrophages. Mar Drugs 14(9):169. https://doi.org/10.3390/md14090169
Zheng Y et al (2020) Protective effect of chitosan oligosaccharide against oxidative damage of peripheral blood mononuclear cells in dairy cows induced by diethylenetriamine/nitric oxide via NF-κB signalling pathway. Ital J Anim Sci 19(1):602–609. https://doi.org/10.1080/1828051X.2020.1772131
Zhou X et al (2010) Effect of low molecular weight chitosans on drug permeation through mouse skin: 1. Transdermal delivery of baicalin. J Pharm Sci 99(7):2991–2998. https://doi.org/10.1002/jps.22063
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Tabassum, N., Ahmed, S., Azam Ali, M. (2022). Chitooligosaccharides for Drug Delivery. In: Kim, SK. (eds) Chitooligosaccharides. Springer, Cham. https://doi.org/10.1007/978-3-030-92806-3_19
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