Physicochemical, pharmaceutical and biological approaches toward designing optimized and efficient hydrophobically modified chitosan-based polymeric micelles as a nanocarrier system for targeted delivery of anticancer drugs

References

• Min KH, Park K, Kim YS, et al. Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy. J Control Release 2008;127:208–18
   PubMed Web of Science ®Google Scholar
• Son YJ, Jang JS, Cho YW, et al. Biodistribution and anti-tumor efficacy of doxorubicin loaded glycol-chitosan nanoaggregates by EPR effect. J Control Release 2003;91:135–45
   PubMed Web of Science ®Google Scholar
• Hwang HY, Kim IS, Kwon IC, Kim YH. Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles. J Control Release 2012;128:23–31
   Google Scholar
• Seow WY, Xue JM, Yang YY. Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles. Biomaterials 2007;28:1730–40
   PubMed Web of Science ®Google Scholar
• Kim SC, Yoon HJ, Lee JW, et al. Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles. Int J Pharm 2005;293:303–10
   PubMed Web of Science ®Google Scholar
• Qu G, Yao Z, Zhang C, et al. PEG conjugated N-octyl-O-sulfate chitosan micelles for delivery of paclitaxel: in vitro characterization and in vivo evaluation. Eur J Pharm Sci 2009;37:98–105
   PubMed Web of Science ®Google Scholar
• Ravi Kumar MNV. A review of chitin and chitosan applications. React Funct Polym 2000;46:1–27
   Web of Science ®Google Scholar
• Kean T, Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv Drug Delivery Rev 2010;62:3–11
   PubMed Web of Science ®Google Scholar
• Wang QZ, Chen XG, Liu N, et al. Protonation constants of chitosan with different molecular weight and degree of deacetylation. Carbohydr Polym 2006;65:194–201
   Web of Science ®Google Scholar
• Bagheri-Khoulenjani S, Taghizadeh S, Mirzadeh H. An investigation on the short-term biodegradability of chitosan with various molecular weights and degrees of deacetylation. Carbohydr Polym 2009;78:773–8
   Web of Science ®Google Scholar
• Qin C, Du Y, Zong L, et al. Effect of hemicellulase on the molecular weight and structure of chitosan. Polym Degrad Stab 2003;80:435–41
   Web of Science ®Google Scholar
• Santander-Ortega M, Peula-García J, Goycoolea F, Ortega-Vinuesa J. Chitosan nanocapsules: effect of chitosan molecular weight and acetylation degree on electrokinetic behaviour and colloidal stability. Colloids Surf B Biointerfaces 2011;82:571–80
   PubMed Web of Science ®Google Scholar
• Du YZ, Wang L, Yuan H, et al. Preparation and characteristics of linoleic acid-grafted chitosan oligosaccharide micelles as a carrier for doxorubicin. Colloids Surf B Biointerfaces 2009;69:257–63
   PubMed Web of Science ®Google Scholar
• Kim YH, Gihm SH, Park CR, et al. Structural characteristics of size-controlled self-aggregates of deoxycholic acid-modified chitosan and their application as a DNA delivery carrier. Bioconjug Chem 2001;12:932–8
   PubMed Web of Science ®Google Scholar
• Huo M, Zhang Y, Zhou J, et al. Formation, microstructure, biodistribution and absence of toxicity of polymeric micelles formed by N-octyl-N,O-carboxymethyl chitosan. Carbohydr Polym 2011;83:1959–69
   Web of Science ®Google Scholar
• Tsaih ML, Chen RH. Effect of molecular weight and urea on the conformation of chitosan molecules in dilute solutions. Int J Biol Macromol 1997;20:233–40
   PubMed Web of Science ®Google Scholar
• Qun G, Ajun W. Effects of molecular weight, degree of acetylation and ionic strength on surface tension of chitosan in dilute solution. Carbohydr Polym 2006;64:29–36
   Web of Science ®Google Scholar
• Li YY, Chen XG, Yu LM, et al. Aggregation of hydrophobically modified chitosan in solution and at the air–water interface. J Appl Polym Sci 2006;102:1968–73
   Web of Science ®Google Scholar
• Zhang J, Chen XG, Li YY, Liu CS. Self-assembled nanoparticles based on hydrophobically modified chitosan as carriers for doxorubicin. Nanomedicine 2007;3:258–65
   PubMed Web of Science ®Google Scholar
• Signini R, Desbrières J, Campana Filho S. On the stiffness of chitosan hydrochloride in acid-free aqueous solutions. Carbohydr Polym 2000;43:351–7
   Web of Science ®Google Scholar
• Rinaudo M, Milas M, Dung PL. Characterization of chitosan. Influence of ionic strength and degree of acetylation on chain expansion. Int J Biol Macromol 1993;15:281–5
   PubMed Web of Science ®Google Scholar
• Anthonsen MW, Vårum KM, Smidsrød O. Solution properties of chitosans: conformation and chain stiffness of chitosans with different degrees of N-acetylation. Carbohydr Polym 1993;22:193–201
   Web of Science ®Google Scholar
• Wang W, Bo S, Li S, Qin W. Determination of the Mark-Houwink equation for chitosans with different degrees of deacetylation. Int J Biol Macromol 1991;13:281–5
   PubMed Web of Science ®Google Scholar
• Schatz C, Viton C, Delair T, et al. Typical physicochemical behaviors of chitosan in aqueous solution. Biomacromolecules 2003b;4:641–8
   PubMed Web of Science ®Google Scholar
• Kim JH, Kim YS, Kim S, et al. Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel. J Control Release 2006;111:228–34
   PubMed Web of Science ®Google Scholar
• Zhang J, Chen XG, Sun GZ, et al. Effect of molecular weight on the oleoyl-chitosan nanoparticles as carriers for doxorubicin. Colloids Surf B Biointerfaces 2010;77:125–30
   PubMed Web of Science ®Google Scholar
• Park K, Kim JH, Nam YS, et al. Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles. J Control Release 2007;122:305–14
   PubMed Web of Science ®Google Scholar
• Jiang G B, Quan D, Liao K, Wang H. Preparation of polymeric micelles based on chitosan bearing a small amount of highly hydrophobic groups. Carbohydr Polym 2006;66:514–20
   Web of Science ®Google Scholar
• Yang X, Zhang Q, Wang Y, et al. Self-aggregated nanoparticles from methoxy poly(ethylene glycol)-modified chitosan: synthesis; characterization; aggregation and methotrexate release in vitro. Colloids Surf B Biointerfaces 2008;61:125–31
   PubMed Web of Science ®Google Scholar
• Fan L, Li F, Zhang H, et al. Co-delivery of PDTC and doxorubicin by multifunctional micellar nanoparticles to achieve active targeted drug delivery and overcome multidrug resistance. Biomaterials 2010;31:5634–42
   PubMed Web of Science ®Google Scholar
• Chen XG, Lee CM, Park HJ. O/W emulsification for the self-aggregation and nanoparticle formation of linoleic acid modified chitosan in the aqueous system. J Agric Food Chem 2003;51:3135–9
   PubMed Web of Science ®Google Scholar
• Pang HT, Chen XG, Park HJ, et al. Preparation and rheological properties of deoxycholate-chitosan and carboxymethyl-chitosan in aqueous systems. Carbohydr Polym 2007;69:419–25
   Web of Science ®Google Scholar
• Amiji MM. Pyrene fluorescence study of chitosan self-association in aqueous solution. Carbohydr Polym 1995;26:211–13
   Web of Science ®Google Scholar
• Lee KY, Jo WH, Kwon IC, et al. Physicochemical characteristics of self-aggregates of hydrophobically modified chitosans. Langmuir 1998;14:2329–32
   Web of Science ®Google Scholar
• Chen WY, Hsu CH, Huang JR, et al. Effect of the ionic strength of the media on the aggregation behaviors of high molecule weight chitosan. J Polym Res 2011b;18:1385–95
   Web of Science ®Google Scholar
• Peng X, Zhang L. Formation and morphologies of novel self-assembled micelles from chitosan derivatives. Langmuir 2007;23:10493–8
   PubMed Web of Science ®Google Scholar
• Cai G, Jiang H. pH-Sensitive nanoparticles self-assembled from a novel class of biodegradable amphiphilic copolymers based on chitosan. J Mater Sci: Mater Med 2009;20:1315–20
   PubMed Web of Science ®Google Scholar
• Yang L, Guo C, Jia L, et al. Dual responsive copolymer micelles for drug controlled release. J Colloid Interface Sci 2010;350:22–9
   PubMed Web of Science ®Google Scholar
• Lao SB, Zhang ZX, Xu HH, Jiang GB. Novel amphiphilic chitosan derivatives: synthesis, characterization and micellar solubilization of rotenone. Carbohydr Polym 2010;82:1136–42
   Web of Science ®Google Scholar
• Du YZ, Lu P, Zhou JP, et al. Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system: factors affecting the complexation. Int J Pharm 2010;391:260–6
   PubMed Web of Science ®Google Scholar
• Yinsong W, Lingrong L, Jian W, Zhang Q. Preparation and characterization of self-aggregated nanoparticles of cholesterol-modified O-carboxymethyl chitosan conjugates. Carbohydr Polym 2007;69:597–606
   Web of Science ®Google Scholar
• Xiangyang X, Ling L, Jianping Z, et al. Preparation and characterization of N-succinyl-N′-octyl chitosan micelles as doxorubicin carriers for effective anti-tumor activity. Colloids Surf B Biointerfaces 2007;55:222–8
   PubMed Web of Science ®Google Scholar
• Peng X, Zhang L. Self-assembled micelles of N-phthaloyl-carboxymethychitosan for drug delivery. Colloids Surf A 2009;337:21–5
   Web of Science ®Google Scholar
• Hu FQ, Meng P, Dai YQ, et al. PEGylated chitosan-based polymer micelle as an intracellular delivery carrier for anti-tumor targeting therapy. Eur J Pharm Biopharm 2008;70:749–57
   PubMed Web of Science ®Google Scholar
• Yoksan R, Matsusaki M, Akashi M, Chirachanchai S. Controlled hydrophobic/hydrophilic chitosan: colloidal phenomena and nanosphere formation. Colloid Polym Sci 2004;282:337–42
   Web of Science ®Google Scholar
• Zhang Y, Huo M, Zhou J, et al. Potential of amphiphilically modified low molecular weight chitosan as a novel carrier for hydrophobic anticancer drug: synthesis, characterization, micellization and cytotoxicity evaluation. Carbohydr Polym 2009;77:231–8
   Web of Science ®Google Scholar
• Hyung Park J, Kwon S, Lee M, et al. Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity. Biomaterials 2006;27:119–26
   PubMed Web of Science ®Google Scholar
• Hu FQ, Wu X, Du YZ, et al. Cellular uptake and cytotoxicity of shell crosslinked stearic acid-grafted chitosan oligosaccharide micelles encapsulating doxorubicin. Eur J Pharm Biopharm 2008;69:117–25
   PubMed Web of Science ®Google Scholar
• Du Y-Z, Wang L, Yuan H, Hu F-Q. Linoleic acid-grafted chitosan oligosaccharide micelles for intracellular drug delivery and reverse drug resistance of tumor cells. Int J Biol Macromol 2011;48:215–22
   PubMed Web of Science ®Google Scholar
• Lin WJ, Chen MH. Synthesis of multifunctional chitosan with galactose as a targeting ligand for glycoprotein receptor. Carbohydr Polym 2007;67:474–80
   Web of Science ®Google Scholar
• Schatz C, Pichot C, Delair T, et al. Static light scattering studies on chitosan solutions: from macromolecular chains to colloidal dispersions. Langmuir 2003;19:9896–903
   Web of Science ®Google Scholar
• Aiping Z, Tian C, Lanhua Y, et al. Synthesis and characterization of N-succinyl-chitosan and its self-assembly of nanospheres. Carbohydr Polym 2006;66:274–9
   Web of Science ®Google Scholar
• Kong XY, Li XY, Wang XH, et al. Synthesis and characterization of a novel MPEG-chitosan diblock copolymer and self-assembly of nanoparticles. Carbohydr Polym 2010;79:170–5
   Web of Science ®Google Scholar
• Mekhail GM, Kamel AO, Awad GA, Mortada ND. Anticancer effect of atorvastatin nanostructured polymeric micelles based on stearyl-grafted chitosan. Int J Biol Macromol 2012;51:351–63
   PubMed Web of Science ®Google Scholar
• Guan X, Quan D, Shuai X, et al. Chitosan graft poly(caprolactone) s: an optimized chemical approach leading to a controllable structure and enhanced properties. J Polym Sci, Part A: Polym Chem 2007;45:2556–68
   Web of Science ®Google Scholar
• Jeong YI, Kim DG, Jang MK, Nah JW. Preparation and spectroscopic characterization of methoxy poly(ethylene glycol)-grafted water-soluble chitosan. Carbohydr Res 2008;343:282–9
   PubMed Web of Science ®Google Scholar
• Ma G, Yang D, Zhou Y, et al. Preparation and characterization of water-soluble N-alkylated chitosan. Carbohydr Polym 2008;74:121–6
   Web of Science ®Google Scholar
• Xiong W-Y, Yi Y, Liu H-Z, et al. Selective carboxypropionylation of chitosan: synthesis, characterization, blood compatibility, and degradation. Carbohydr Res 2011;346:1217–23
   PubMed Web of Science ®Google Scholar
• Pillai C, Paul W, Sharma CP. Chitin and chitosan polymers: chemistry, solubility and fiber formation. Prog Polym Sci 2009;34:641–78
   Web of Science ®Google Scholar
• Zou A, Huo M, Yin X, et al. Octreotide-mediated N-octyl-O, N-carboxymethyl chitosan micelles: preparation, characterization and research as doxorubicin delivery vectors. J China Pharm Univ 2011;42:124–30
   Google Scholar
• Huo M, Zou A, Yao C, et al. Somatostatin receptor-mediated tumor-targeting drug delivery using octreotide-PEG-deoxycholic acid conjugate-modified N-deoxycholic acid-O, N-hydroxyethylation chitosan micelles. Biomaterials 2012;33:6393–407
   PubMed Web of Science ®Google Scholar
• Ma G, Yang D, Kennedy JF, Nie J. Synthesize and characterization of organic-soluble acylated chitosan. Carbohydr Polym 2009;75:390–4
   Web of Science ®Google Scholar
• Gorochovceva N, Makuka R. Synthesis and study of water-soluble chitosan-O-poly(ethylene glycol) graft copolymers. Eur Polym J 2004;40:685–91
   Web of Science ®Google Scholar
• Hu Y, Du Y, Yang J, et al. Self-aggregation and antibacterial activity of N-acylated chitosan. Polymer 2007;48:3098–106
   Web of Science ®Google Scholar
• Hu Y, Du Y, Wang X, Feng T. Self aggregation of water soluble chitosan and solubilization of thymol as an antimicrobial agent. J Biomed Mater Res Part A 2009;90:874–81
   PubMedGoogle Scholar
• Zhang C, Ding Y, Yu LL, Ping Q. Polymeric micelle systems of hydroxycamptothecin based on amphiphilic N-alkyl-N-trimethyl chitosan derivatives. Colloids Surf B Biointerfaces 2007;55:192–9
   PubMed Web of Science ®Google Scholar
• Saravanakumar G, Min KH, Min DS, et al. Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: synthesis, characterization, and in vivo biodistribution. J Control Release 2009;140:210–17
   PubMed Web of Science ®Google Scholar
• Huo M, Zhang Y, Zhou J, et al. Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug. Int J Pharm 2010;394:162–73
   PubMed Web of Science ®Google Scholar
• Kohori F, Yokoyama M, Sakai K, Okano T. Process design for efficient and controlled drug incorporation into polymeric micelle carrier systems. J Control Release 2002;78:155–63
   PubMed Web of Science ®Google Scholar
• Zhang C, Qineng P, Zhang H. Self-assembly and characterization of paclitaxel-loaded N-octyl-O-sulfate chitosan micellar system. Colloids Surf B Biointerfaces 2004;39:69–75
   PubMed Web of Science ®Google Scholar
• Sui W, Changqing Y, Yanjing C, et al. Self-assembly of an amphiphilic derivative of chitosan and micellar solubilization of puerarin. Colloids Surf B Biointerfaces 2006;48:13–16
   PubMed Web of Science ®Google Scholar
• Duhem N, Rolland J, Riva R, et al. Tocol modified glycol chitosan for the oral delivery of poorly soluble drugs. Int J Pharm 2012;423:452–60
   PubMed Web of Science ®Google Scholar
• Jiang GB, Quan D, Liao K, Wang H. Novel polymer micelles prepared from chitosan grafted hydrophobic palmitoyl groups for drug delivery. Mol Pharm 2006;3:152–60
   PubMed Web of Science ®Google Scholar
• Kim JH, Kim YS, Park K, et al. Self-assembled glycol chitosan nanoparticles for the sustained and prolonged delivery of antiangiogenic small peptide drugs in cancer therapy. Biomaterials 2008;29:1920–30
   PubMed Web of Science ®Google Scholar
• Yu JM, Li YJ, Qiu LY, Jin Y. Self-aggregated nanoparticles of cholesterol-modified glycol chitosan conjugate: preparation, characterization, and preliminary assessment as a new drug delivery carrier. Eur Polym J 2008;44:555–65
   Web of Science ®Google Scholar
• Li Y, Zhang S, Meng X, et al. The preparation and characterization of a novel amphiphilic oleoyl-carboxymethyl chitosan self-assembled nanoparticles. Carbohydr Polym 2011;83:130–6
   Web of Science ®Google Scholar
• Ngawhirunpat T, Wonglertnirant N, Opanasopit P, et al. Incorporation methods for cholic acid chitosan-g-mPEG self-assembly micellar system containing camptothecin. Colloids Surf B Biointerfaces 2009;74:253–9
   PubMed Web of Science ®Google Scholar
• Zheng H, Rao Y, Yin Y, et al. Preparation, characterization, and in vitro drug release behavior of 6-mercaptopurine-carboxymethyl chitosan. Carbohydr Polym 2011;83:1952–8
   Web of Science ®Google Scholar
• Park JH, Cho YW, Son YJ, et al. Preparation and characterization of self-assembled nanoparticles based on glycol chitosan bearing adriamycin. Colloid Polym Sci 2006;284:763–70
   Web of Science ®Google Scholar
• Lee K, Kim JH, Kwon I, Jeong S. Self-aggregates of deoxycholic acid-modified chitosan as a novel carrier of adriamycin. Colloid Polym Sci 2000;278:1216–19
   Web of Science ®Google Scholar
• Zhang C, Qu G, Sun Y, et al. Pharmacokinetics, biodistribution, efficacy and safety of N-octyl-O-sulfate chitosan micelles loaded with paclitaxel. Biomaterials 2008;29:1233–41
   PubMed Web of Science ®Google Scholar
• Na JH, Koo H, Lee S, et al. Real-time and non-invasive optical imaging of tumor-targeting glycol chitosan nanoparticles in various tumor models. Biomaterials 2011;32:5252–61
   PubMed Web of Science ®Google Scholar
• Huh KM, Lee SC, Cho YW, et al. Hydrotropic polymer micelle system for delivery of paclitaxel. J Control Release 2005;101:59–68
   PubMed Web of Science ®Google Scholar
• Liu L, Xu X, Guo S, Han W. Synthesis and self-assembly of chitosan-based copolymer with a pair of hydrophobic/hydrophilic grafts of polycaprolactone and poly(ethylene glycol). Carbohydr Polym 2009;75:401–7
   Web of Science ®Google Scholar
• Yuan H, Lu L-J, Du Y-Z, Hu F-Q. Stearic acid-g-chitosan polymeric micelle for oral drug delivery: in vitro transport and in vivo absorption. Mol Pharm 2010;8:225–38
   PubMed Web of Science ®Google Scholar
• Wang Y, Jiang Q, Liu LR, Zhang Q. The interaction between bovine serum albumin and the self-aggregated nanoparticles of cholesterol-modified O-carboxymethyl chitosan. Polymer 2007;48:4135–42
   Web of Science ®Google Scholar
• Cai G, Zhang H, Liu P, et al. Triggered disassembly of hierarchically assembled onion-like micelles into the pristine core–shell micelles via a small change in pH. Acta Biomater 2011;7:3729–37
   PubMed Web of Science ®Google Scholar
• Chen M, Liu Y, Yang W, et al. Preparation and characterization of self-assembled nanoparticles of 6-O-cholesterol-modified chitosan for drug delivery. Carbohydr Polym 2011;84:1244–51
   Web of Science ®Google Scholar
• Wang YS, Liu LR, Jiang Q, Zhang QQ. Self-aggregated nanoparticles of cholesterol-modified chitosan conjugate as a novel carrier of epirubicin. Eur Polym J 2007;43:43–51
   Web of Science ®Google Scholar
• Ye YQ, Chen FY, Wu Q, et al. Enhanced cytotoxicity of core modified chitosan based polymeric micelles for doxorubicin delivery. J Pharm Sci 2009;98:704–12
   PubMed Web of Science ®Google Scholar
• Li H, Liu J, Ding S, et al. Synthesis of novel pH-sensitive chitosan graft copolymers and micellar solubilization of paclitaxel. Int J Biol Macromol 2009;44:249–56
   PubMed Web of Science ®Google Scholar
• Park JS, Han TH, Lee KY, et al. N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs: endocytosis, exocytosis and drug release. J Control Release 2006;115:37–45
   PubMed Web of Science ®Google Scholar
• Mo R, Jin X, Li N, et al. The mechanism of enhancement on oral absorption of paclitaxel by N-octyl-O-sulfate chitosan micelles. Biomaterials 2011;32:4609–20
   PubMed Web of Science ®Google Scholar
• Li H, Huo M, Zhou J, et al. Enhanced oral absorption of paclitaxel in N deoxycholic acid N, O hydroxyethyl chitosan micellar system. J Pharm Sci 2010;99:4543–53
   PubMed Web of Science ®Google Scholar
• Mo R, Xiao Y, Sun M, et al. Enhancing effect of N-octyl-O-sulfate chitosan on etoposide absorption. Int J Pharm 2011;409:38–45
   PubMed Web of Science ®Google Scholar
• Kim JH, Kim YS, Park K, et al. Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice. J Control Release 2008b;127:41–9
   PubMed Web of Science ®Google Scholar
• Cho YW, Park SA, Han TH, et al. In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: mechanisms, key factors, and their implications. Biomaterials 2007;28:1236–47
   PubMed Web of Science ®Google Scholar
• Zhu H, Liu F, Guo J, et al. Folate-modified chitosan micelles with enhanced tumor targeting evaluated by near infrared imaging system. Carbohydr Polym 2011;86:1118–29
   Web of Science ®Google Scholar
• Hobbs SK, Monsky WL, Yuan F, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA 1998;95:4607–12
   PubMed Web of Science ®Google Scholar
• Lee BS, Park K, Park S, et al. Tumor targeting efficiency of bare nanoparticles does not mean the efficacy of loaded anticancer drugs: importance of radionuclide imaging for optimization of highly selective tumor targeting polymeric nanoparticles with or without drug. J Control Release 2010;147:253–60
   PubMed Web of Science ®Google Scholar
• Lee C-M, Jang D, Kim J, et al. Oleyl-chitosan nanoparticles based on a dual probe for optical/MR imaging in vivo. Bioconjug Chem 2011;22:186–92
   PubMed Web of Science ®Google Scholar
• Wang F, Zhang D, Duan C, et al. Preparation and characterizations of a novel deoxycholic acid–O-carboxymethylated chitosan–folic acid conjugates and self-aggregates. Carbohydr Polym 2011;84:1192–200
   Web of Science ®Google Scholar
• Tan Y-L, Liu C-G. Preparation and characterization of self-assemblied nanoparticles based on folic acid modified carboxymethyl chitosan. J Mater Sci: Mater Med 2011;22:1213–20
   PubMed Web of Science ®Google Scholar
• Zhang C, Qu G, Sun Y, et al. Biological evaluation of N-octyl-O-sulfate chitosan as a new nano-carrier of intravenous drugs. Eur J Pharm Sci 2008b;33:415–23
   PubMed Web of Science ®Google Scholar
• Onishi H, Machida Y. Biodegradation and distribution of water-soluble chitosan in mice. Biomaterials 1999;20:175–82
   PubMed Web of Science ®Google Scholar
• Kato Y, Onishi H, Machida Y. Evaluation of N-succinyl-chitosan as a systemic long-circulating polymer. Biomaterials 2006;21:1579–85
   Google Scholar
• Kato Y, Onishi H, Machida Y. N-succinyl-chitosan as a drug carrier: water-insoluble and water-soluble conjugates. Biomaterials 2004;25:907–15
   PubMed Web of Science ®Google Scholar
• Kato Y, Onishi H, Machida Y. Biological fate of highly-succinylated N-succinyl-chitosan and antitumor characteristics of its water-soluble conjugate with mitomycin C at iv and ip administration into tumor-bearing mice. Biol Pharm Bull 2000;23:1497–503
   PubMed Web of Science ®Google Scholar
• Zeng L, Qin C, Wang W, et al. Absorption and distribution of chitosan in mice after oral administration. Carbohydr Polym 2008;71:435–40
   Web of Science ®Google Scholar
• Kim J-H, Bae SM, Na M-H, et al. Facilitated intracellular delivery of peptide-guided nanoparticles in tumor tissues. J Control Release 2012;157:493–9
   PubMed Web of Science ®Google Scholar
• Nam HY, Kwon SM, Chung H, et al. Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles. J Control Release 2009;135:259–67
   PubMed Web of Science ®Google Scholar
• Chiu YL, Ho YC, Chen YM, et al. The characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan. J Control Release 2010;146:152–9
   PubMed Web of Science ®Google Scholar
• Qu D, Lin H, Zhang N, et al. In vitro evaluation on novel modified chitosan for targeted antitumor drug delivery. Carbohydr Polym 2012;92:545–54
   PubMed Web of Science ®Google Scholar
• Zhang J, Chen XG, Peng WB, Liu CS. Uptake of oleoyl-chitosan nanoparticles by Acells. Nanomedicine 2008c;4:208–14
   PubMed Web of Science ®Google Scholar
• Cho YW, Kim Y, Kim I, et al. Tumoral accumulation of long-circulating, self-assembled nanoparticles and its visualization by gamma scintigraphy. Macromol Res 2008;16:15–20
   Web of Science ®Google Scholar
• Lee SJ, Koo H, Jeong H, et al. Comparative study of photosensitizer loaded and conjugated glycol chitosan nanoparticles for cancer therapy. J Control Release 2011;152:21–9
   PubMed Web of Science ®Google Scholar