Abstract
A novel injectable thermosensitive hydrogel system composed of N-trimethyl chitosan chloride (TMC) and β-glycerophosphate (β-GP), coded as TMC/β-GP, was designed. The morphology and rheological behavior of hydrogels were characterized by scanning electron microscopy and rheometer, respectively. Their swelling properties were carefully studied. The results revealed that the TMC/β-GP system was liquid with low viscosity at low temperature, which allowed it to be an ideal injectable material for biomedical applications. It was interesting that the system kept in liquid status for a long time near 4 °C and transformed rapidly to gel status within 1 min upon heating to 37 °C. The hydrogel could be dissolved at acid pH, while it absorbed water at neutral and basic conditions. The release of BSA from TMC/β-GP gels was slow at neutral pH. The TMC/β-GP hydrogel is a promising vehicle for the drug release, tissue repairing and regeneration.
Similar content being viewed by others
References
Ruel-Gariépy E, Leroux JC (2004) In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm 58:409–426
Sun L, Du Y, Fan L et al (2006) Preparation, characterization and antimicrobial activity of quaternized carboxymethyl chitosan and application as pulp-cap. Polymer 47:1796–1804
Khor E, Lim LY (2003) Implantable applications of chitin and chitosan. Biomaterials 24:2339–2349
Prashanth KVH, Tharanathan RN (2007) Chitin/chitosan: modifications and their unlimited application potential—an overview. Trends Food Sci Tech 18:117–131
Kim IY, Seo SJ, Moon HS et al (2008) Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv 26:1–21
Qin C, Li H, Xiao Q et al (2006) Water-solubility of chitosan and its antimicrobial activity. Carbohydr Polym 63:367–374
Borchard G (2001) Chitosans for gene delivery. Adv Drug Deliver Rev 52:145–150
Chenite A, Buschmann M, Wang D et al (2001) Rheological characterization of thermogelling chitosan/glycerol-phosphate solutions. Carbohydr Polym 46:39–47
Chenite A, Chaput C, Wang D et al (2000) Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 21:2155–2161
Ruel-Gariépy E, Chenite A, Chaput C et al (2000) Characterization of thermosensitive chitosan gels for the sustained delivery of drugs. Int J Pharm 203:89–98
Alvarez-Lorenzo C, Concheiro A, Dubovik AS et al (2005) Temperature-sensitive chitosan-poly(N-isopropylacrylamide) interpenetrated networks with enhanced loading capacity and controlled release properties. J Control Release 102:629–641
Bhattarai N, Ramay HR, Gunn J et al (2005) PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release. J Control Release 103:609–624
Wu J, Su ZG, Ma GH (2006) A thermo- and pH-sensitive hydrogel composed of quaternized chitosan/glycerophosphate. Int J Pharm 315:1–11
Tang YF, Du YM, Hu XW et al (2007) Rheological characterisation of a novel thermosensitive chitosan/poly(vinyl alcohol) blend hydrogel. Carbohydr Polym 67:491–499
Mu Q, Fang Y (2008) Preparation of thermosensitive chitosan with poly(N-isopropylacrylamide) side at hydroxyl group via O-maleoyl-N-phthaloyl-chitosan (MPCS). Carbohydr Polym 72:308–314
Kotzé AF, Lueβen HL, de Leeuw BJ et al (1998) Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of the intestinal epithelial cells (Caco-2). J Control Release 51:35–46
Hamman JH, Stander M, Kotzé AF (2002) Effect of the degree of quaternisation of N-trimethyl chitosan chloride on absorption enhancement: in vivo evaluation in rat nasal epithelia. Int J Pharm 232:235–242
van der Merwe SM, Verhoef JC, Verheijden JHM et al (2004) Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs. Eur J Pharm Biopharm 58:225–235
Florea BI, Thanou M, Junginger HE et al (2006) Enhancement of bronchial octreotide absorption by chitosan and N-trimethyl chitosan shows linear in vitro/in vivo correlation. J Control Release 110:353–361
Amidi M, Romeijn SG, Borchard G et al (2006) Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release 111:107–116
Chen F, Zhang ZR, Huang Y (2007) Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm 336:166–173
Peng X, Zhang L (2008) Encapsulation of bovine serum albumin in N-methyl chitosan microspheres. J Biobased Mater Bioenergy 2:64–70
Sieval AB, Thanou M, Kotzé AF et al (1998) Preparation and NMR characterization of highly substituted N-trimethyl chitosan chloride. Carbohydr Polym 36:157–165
Snyman D, Hamman JH, Kotze JS et al (2002) The relationship between the absolute molecular weight and the degree of quaternisation of N-trimethyl chitosan chloride. Carbohydr Polym 50:145–150
Lue A, Zhang L (2008) Investigation of the scaling law on cellulose solution prepared at low temperature. J Phys Chem B 112:4488–4495
Chen L, Tian Z, Du Y (2004) Synthesis and pH sensitivity of carboxymethyl chitosan-based polyampholyte hydrogels for protein carrier matrices. Biomaterials 25:3725–3732
Zhao Y, Dai Y, Cui X et al (2006) Determination of protein contents of radix aconiti kusnezoffii using Coomassie Brilliant Blue G-250 dye binding. J Yunnan Natl Univ (Nat Sci Ed) 15:235–237
Xu Y, Du Y, Huang R et al (2003) Preparation and modification of N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride nanoparticle as a protein carrier. Biomaterials 24:5015–5022
Jia Z, Shen D, Xu W (2001) Synthesis and antibacterial activities of quaternary ammonium salt of chitosan. Carbohydr Res 333:1–6
Ruan D, Lue A, Zhang L (2008) Gelation behaviors of cellulose solution dissolved in aqueous NaOH/thiourea at low temperature. Polymer 49:1027–1036
Lee KY, Yuk SH (2007) Polymeric protein delivery systems. Prog Polym Sci 32:669–697
Acknowledgment
This work was supported by the National Natural Science Foundation of China (No. 30571462).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chang, Y., Xiao, L. & Du, Y. Preparation and properties of a novel thermosensitive N-trimethyl chitosan hydrogel. Polym. Bull. 63, 531–545 (2009). https://doi.org/10.1007/s00289-009-0103-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00289-009-0103-6