Stability of chitosan - A challenge for pharmaceutical and biomedical applications

Marine Drugs

Volumn 13, Issue 4, 2015, Pages 1819-1846

  Szymańska, Emilia ^a   Winnicka, Katarzyna ^a  

^a MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

Author keywords

Acidic hydrolysis; Chitosan; Drug delivery system; Long term stability; Storage conditions; Thermal degradation

Indexed keywords

BIMATOPROST; BUSPIRONE; CHITOSAN; CHLORAMPHENICOL; CISPLATIN; CITRIC ACID; CLOTRIMAZOLE; DEXTRAN SULFATE; DICLOFENAC POTASSIUM; FUCOIDIN; GLYCEROL 2 PHOSPHATE; INSULIN; METRONIDAZOLE; MICROSPHERE; NANOCONJUGATE; NANOPARTICLE; OVALBUMIN; POLYMER; PROMETHAZINE; XANTHAN; CROSS LINKING REAGENT; EXCIPIENT;

ANXIETY DISORDER; BIODEGRADABILITY; BIOMEDICAL ENGINEERING; BONE TISSUE; CANDIDIASIS; CARTILAGE CELL; CHEMICAL STRUCTURE; COMPLEX FORMATION; CROSS LINKING; DEACETYLATION; DIABETES MELLITUS; DISPERSION; DISSOLUTION; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM; DRUG FORMULATION; DRY POWDER INHALER; ENVIRONMENTAL FACTOR; FREEZE DRYING; GAMMA IRRADIATION; GEL; GLAUCOMA; HEATING; HUMIDITY; HYDROGEL; HYDROLYSIS; LUNG CANCER; MIGRAINE; MOISTURE; MOLECULAR WEIGHT; MUCOADHESION; PERIODONTAL DISEASE; PHARMACEUTICAL ENGINEERING; PHARMACEUTICS; PHYSICAL CHEMISTRY; REVIEW; SHELF LIFE; SPRAY DRYING; SUSTAINED RELEASE FORMULATION; TISSUE ENGINEERING; ULTRAVIOLET RADIATION; VISCOSITY; WOUND; ADVERSE EFFECTS; ANALOGS AND DERIVATIVES; ANIMAL; CARBOHYDRATE ANALYSIS; CHEMISTRY; DRUG STABILITY; DRUG STORAGE; HEAT; HUMAN; TISSUE SCAFFOLD; TRENDS;

ANIMALS; CARBOHYDRATE SEQUENCE; CHITOSAN; CROSS-LINKING REAGENTS; DRUG COMPOUNDING; DRUG DELIVERY SYSTEMS; DRUG STABILITY; DRUG STORAGE; EXCIPIENTS; HOT TEMPERATURE; HUMANS; HYDROLYSIS; MOLECULAR WEIGHT; TISSUE ENGINEERING; TISSUE SCAFFOLDS;

EID: 84928384274     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md13041819     Document Type: Review

References (119)

1. D'Ayala, G.G.; Malinconico, M.; Laurienzo, P. Marine derived polysaccharides for biomedical applications: Chemical modification approaches. Molecules 2008, 13, 2069-2106.
2. Laurienzo, P. Marine polysaccharides in pharmaceutical applications: An overview. Mar. Drugs 2010, 8, 2435-2465.
3. Saravanakumar, G.; Jo, D.G.; Park, J.H. Polysaccharide-based nanoparticles: A versatile platform for drug delivery and biomedical imaging. Curr. Med. Chem. 2012, 19, 3212-3229.
4. Szymańska, E.; Winnicka, K. Preparation and in vitro evaluation of chitosan microgranules with clotrimazole. Acta Pol. Pharm. Drug Res. 2012, 69, 509-513.
5. Hurler, J.; Škalko-Basnet, N. Potentials of chitosan-based delivery systems in wound therapy: Bioadhesion study. J. Funct. Biomater. 2012, 3, 37-48.
6. Okamoto, Y.; Yano, R.; Miyatake, K.; Tomohiro, I.; Shigemasa, Y.; Minami, S. Effects of chitin and chitosan on blood coagulation. Carbohydr. Polym. 2003, 53, 337-342.
7. Kim, I.Y.; Seo, S.J.; Moon, H.S.; Yoo, M.K.; Park, I.Y.; Kim, B.C.; Cho, C.S. Chitosan and its derivatives for tissue engineering applications. Biotechnol. Adv. 2008, 26, 1-21.
8. Venkatesan, J.; Bhatnagar, I.; Kim, S.K. Chitosan-alginate biocomposite containing fucoidan for bone tissue engineering. Mar. Drugs 2014, 12, 300-316.
9. Hoemann, C.D.; Sun, J.; Légaré, A.; McKee, M.D.; Buschmann, M.D. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cartilage 2005, 13, 318-329.
10. Dash, M.; Chiellini, F.; Ottenbrite, R.M.; Chiellini, E. Chitosan - A versatile semi-synthetic polymer in biomedical applications. Prog. Polym. Sci. 2011, 36, 981-1014.
11. Ifuku, S. Chitin and chitosan nanofibers: Preparation and chemical modifications. Molecules 2014, 19, 18367-18380.
12. Mucha, M. Rheological characteristics of semi-dilute chitosan solutions. Macromol. Chem. Phys. 1997, 198, 471-484.
13. Kassem, M.A.; ElMeshad, A.N.; Fares, A.R. Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: Formulation and in vitro evaluation. AAPS Pharm. Sci. Tech. 2014, 6, 1-11.
14. Dehghan, M.H.G.; Kazi, M. Lyophilized chitosan/xanthan polyelectrolyte complex based mucoadhesive inserts for nasal delivery of promethazine hydrochloride. Iran. J. Pharm. Res. 2014, 13, 769-784.
15. Franca, J.R.; Foureaux, G.; Fuscaldi, L.L.; Ribeiro, T.G.; Rodrigues, L.B.; Bravo, R.; Castilho, R.O.; Yoshida, M.I.; Cardoso, V.N.; Fernandes, S.O.; et al. Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation. PLoS ONE 2014, 9, e95461-e95472.
16. Szymańska, E.; Winnicka, K.; Amelian, A.; Cwalina, U. Vaginal chitosan tablets with clotrimazole-design and evaluation of mucoadhesive properties using porcine vaginal mucosa, mucin and gelatin. Chem. Pharm. Bull. 2014, 62, 160-167.
17. Yeh, T.H.; Hsu, L.W.; Tseng, M.T.; Lee, P.L.; Sonjae, K.; Ho, Y.C.; Sung, H.W. Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening. Biomaterials 2011, 32, 6164-6173.
18. Slütter, B.; Bal, S.M.; Que, I.; Kaijzel, E.; Löwik, C.; Bouwstra, J.; Jiskoot, W. Antigen-adjuvant nanoconjugates for nasal vaccination: An improvement over the use of nanoparticles? Mol. Pharm. 2010, 7, 2207-2215.
19. Bal, S.M.; Slütter, B.; Verheul, R.; Bouwstra, J.A.; Jiskoot, W. Adjuvanted, antigen loaded N-trimethyl chitosan nanoparticles for nasal and intradermal vaccination: Adjuvant- and site-dependent immunogenicity in mice. Eur. J. Pharm. Sci. 2012, 45, 475-481.
20. Van der Lubben, I.M.; Kersten, G.; Fretz, M.M.; Beuvery, C.; Coos Verhoef, J.; Junginger, H.E. Chitosan microparticles for mucosal vaccination against diphtheria: Oral and nasal efficacy studies in mice. Vaccine 2003, 21, 1400-1408.
21. Baker, W.L.; Tercius, A.; Anglade, M.; White, C.M.; Coleman, C.I. A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients. Ann. Nutr. Metabl. 2009, 55, 368-374.
22. Akncbay, H.; Senel, S.; Ay, Z.Y. Application of chitosan gel in the treatment of chronic periodontitis. J. Biomed. Mater. Res. B Appl. Biomater. 2007, 80, 290-296.
23. Kong, M.; Chen, X.G.; Xing, K.; Park, H.J. Antimicrobial properties of chitosan and mode of action: A state of the art review. Int. J. Food Microbiol. 2010, 144, 51-63.
24. Palmeira-de-Oliveira, A.; Ribeiro, M.P.; Palmeira-de-Oliveira, R.; Gaspar, C.; Costa-de-Oliveira, S.; Correia, I.J.; Pina, V.; Martinez-de-Oliveira, J.; Queiroz, J.A.; Rodrigues, A.G. Anti-Candida activity of a chitosan hydrogel: Mechanism of action and cytotoxicity profile. Gynecol. Obstet. Invest. 2010, 70, 322-327.
25. Szymańska, E.; Winnicka, K.; Wieczorek, P.; Sacha, P.T.; Tryniszewska, E.A. Influence of unmodified and beta-glycerophosphate cross-linked chitosan on anti-Candida activity of clotrimazole in semi-solid delivery systems. Int. J. Mol. Sci. 2014, 15, 17765-17777.
26. Perioli, L.; Ambrogi, V.; Pagano, C.; Scuota, S.; Rossi, C. FC90 chitosan as a new polimer for metronidazole mucoadhesive tablets for vaginal administration. Int. J. Pharm. 2009, 377, 120-127.
27. Supper, S.; Anton, N.; Boisclair, J.; Seidel, N.; Riemenschnitter, M.; Curdy, C.; Vandamme, T. Chitosan/glucose 1-phosphate as new stable in situ forming depot system for controlled drug delivery. Eur. J. Pharm. Biopharm. 2014, 88, 361-373.
28. Singh, D.J.; Lohade, A.A.; Parmar, J.J.; Hegde, D.D.; Soni, P.; Samad, A.; Menon, M.D. Development of chitosan-based dry powder inhalation system of cisplatin for lung cancer. Indian J. Pharm. Sci . 2012, 74, 521-526.
29. Sarmento, B.; Ribeiro, A.; Veiga, F.; Ferreira, D. Development and characterization of new insulin containing polysaccharide nanoparticles. Colloids Surf. B Biointerfaces 2006, 53, 193-202.
30. Kurita, K.; Kaji, Y.; Mori, T.; Nishiyama, Y. Enzymatic degradation of β-chitin: Susceptibility and the influence of deacetylation. Carbohydr. Polym. 2000, 42, 19-21.
31. Ma, Z.; Wang, W.; Wu, Y.; He, Y.; Wu, T. Oxidative degradation of chitosan to the low molecular water-soluble chitosan over peroxotungstate as chemical scissors. PLoS ONE 2014, 9, e100743-e100750.
32. Mucha, M.; Pawlak, A. Complex study on chitosan degradability. Polymer 2002, 47, 43-51.
33. Knapczyk, J. Antimycotic buccal and vaginal tablets with chitosan. Int. J. Pharm. 1992, 88, 9-14.
34. Kam, H.M.; Khor, E.; Lim, L.Y. Storage of partially deacetylated chitosan films. J. Biomed. Mater. Res. 1999, 48, 881-888.
35. Jones, C.; Crane, D.T.; Lemercinier, X.; Bolgiano, B.; Yost, S.E. Physicochemical studies of the structure and stability of polysaccharide-protein conjugate vaccines. Dev. Biol. Stand. 1996, 87, 143-151.
36. nd ed.; Dumitriu, S., Ed.; CRC Press: London, UK, 2004; Chapter 14, pp. 395-409.
37. Howling, S.E. Some observations on the effect of bioprocessing on biopolymer stability. J. Drug Target. 2010, 18, 732-740.
38. th ed.; Council of Europe: Strasburg, France, 2007; Volume 2, pp. 1490-1491.
39. The United States Pharmacopeia ; USP 34-NF 29; The United States Pharmacopeial Convention: Rockville, MD, USA, 2011; pp. 5361-5365, Second Supplement.
40. Aranaz, I.; Mengíbar, M.; Harris, R.; Paños, I.; Miralles, B.; Acosta, N.; Galed, G.; Heras, Á. Functional characterization of chitin and chitosan. Curr. Chem. Biol. 2009, 3, 203-230.
41. Tsaih, M.L.; Chen, R.H. The effect of reaction time and temperature during heterogenous alkali deacetylation on degree of deacetylation and molecular weight of resulting chitosan. J. Appl. Polym. Sci. 2003, 88, 2917-2923.
42. rd ed.; Swarbrick, J., Ed.; Informa Healthcare: New York, NY, USA, 2007; Volume 1, pp. 176-193.
43. Dimonie, D.; Dima, S.O.; Petrache, M. Influence of centrifugation on the molecular parameters of chitosan solubilized in weakly acidic aqueous solutions. Dig. J. Nanomater. Bios . 2013, 8, 1799-1809.
44. Buys, G.M.; du Plessis, L.H.; Marais, A.F.; Kotze, A.F.; Hamman, J.H. Direct compression of chitosan: Process and formulation factors to improve powder flow and tablet performance. Curr. Drug Deliv. 2013, 10, 348-356.
45. Weinhold, M.X.; Sauvageau, J.C.M.; Kumirska, J.; Thöming, J. Studies on acetylation patterns of different chitosan preparations. Carbohydr. Polym. 2009, 78, 678-684.
46. Zhang, H.; Neau, S.H. In vitro degradation of chitosan by a commercial enzyme preparation: Effect of molecular weight and degree of deacetylation. Biomaterials 2001, 22, 1653-1658.
47. Francis, S.; Matthew, J.K.; Howard, W.T. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: A review. Biomaterials 2000, 21, 2589-2598.
48. Yuan, Y.; Chesnutt, B.M.; Haggard, W.O.; Bumgardner, J.D. Deacetylation of chitosan: Material characterization and in vitro evaluation via albumin adsorption and pre-osteoblastic cell cultures. Materials 2011, 4, 1399-1416.
49. Vårum, K.M.; Ottøy, M.H.; Smisrød, O. Acid hydrolysis of chitosan. Carbohydr. Polym. 2001, 46, 89-98.
50. Lopez, F.A.; Merce, A.L.R.; Alguacil, F.J.; Lopez-Delgado, A. A kinetic study on the thermal behaviour of chitosan. J. Therm. Anal. Calorim. 2008, 91, 633-639.
51. Wanjun, T.; Cunxin, W.; Donghua, C. Kinetic studies on the pyrolysis of chitin and chitosan. Polym. Degrad. Stab. 2005, 87, 389-394.
52. Bajer, D.; Kaczmarek, H. Study of the influence on UV radiation on biodegradable blends based on chitosan and starch. Progr. Chem. Appl. Chitin Deriv. 2010, 15, 17-24.
53. Davydova, V.N.; Yermak, I.M.; Gorbach, V.I.; Krasikova, I.N.; Solov'eva, T.F. Interaction of bacterial endotoxins with chitosan. Effect of endotoxin structure, chitosan molecular mass, and ionic strength of the solution on the formation of the complex. Biochemistry (Mosc.) 2000, 65, 1082-1090.
54. Gocho, H.; Shimizu, H.; Tanioka, A.; Chou, T.J.; Nakajima, T. Effect of polymer chain end on sorption isotherm of water by chitosan. Carbohydr. Polym. 2000, 41, 87-90.
55. Rege, P.R.; Shukla, D.J.; Block, L.H. Chitinosans as tableting excipients for modified release delivery systems. Int. J. Pharm. 1999, 181, 49-60.
56. Mucha, M.; Ludwiczak, S.; Kawińska, M. Kinetics of water sorption by chitosan and its blends with poly(vinyl alcohol). Carbohydr. Polym. 2005, 62, 42-49.
57. Garr, J.M.S.; Rubinstein, M.H. The influence of moisture content on the consolidation and compaction properties of paracetamol. Int. J. Pharm. 1992, 81, 187-192.
58. No, H.K.; Prinyawiwatkul, W. Stability of chitosan powder during long-term storage at room temperature. J. Agric. Food Chem. 2009, 57, 8434-8438.
59. Viljoen, J.M.; Steenekamp, J.H.; Marais, A.F.; Kotzé, A.F. Effect of moisture content, temperature and exposure time on the physical stability of chitosan powder and tablets. Drug Dev. Ind. Pharm. 2014, 40, 730-742.
60. rd ed.; Swarbrick, J., Ed.; Informa Healthcare: New York, NY, USA, 2007; Volume 4, pp. 2368-2383.
61. Chooi, K.W.; Simão Carlos, M.I.; Soundararajan, R.; Gaisford, S.; Arifin, N.; Schätzlein, A.G.; Uchegbu, I.F. Physical characterisation and long-term stability studies on quaternary ammonium palmitoyl glycol chitosan (GCPQ)-a new drug delivery polymer. J. Pharm. Sci. 2014, 103, 2296-2306.
62. EMA: Stability testing of new drug substances and products. Available online: http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2013/01/WC 500002651.pdf (ICH Topic Q1A R2) (accessed on 10 February 2015).
63. Despond, S.; Espuche, E.; Domard, A. Water sorption and permeation in chitosan films: Relation between gas permeability and relative humidity. J. Polym. Sci. B Polym. Phys. 2001, 39, 3114-3127.
64. Cervera, M.F.; Karjalainen, M.; Airaksinen, S.; Rantanen, J.; Krogars, K.; Heinämäki, J.; Colarte, A.I.; Yliruusi, J. Physical stability and moisture sorption of aqueous chitosan-amylose starch films plasticized with polyols. Eur. J. Pharm. Biopharm. 2004, 58, 69-76.
65. Kurek, M.; Guinault, A.; Voilley, A.; Galić, K.; Debeaufort, F. Effect of relative humidity on carvacrol release and permeation properties of chitosan based films and coatings. Food Chem. 2014, 144, 9-17.
66. Smart, J.D. The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev. 2005, 57, 1556-1568.
67. Nguyen; T.T.B.; Hein, S.; Ng, C.H.; Stevens, W.F. Molecular stability of chitosan in acid solutions stored at various conditions. J. Appl. Polym. Sci. 2008, 107, 2588-2593.
68. Il'ina, A.V.; Varlamov, V.P. Hydrolysis of chitosan in lactic acid. Appl. Biochem. Microbiol. 2004, 40, 300-303.
69. Jarry, C.; Chaput, C.; Chenite, A.; Renaud, M.A.; Buschmann, M.; Leroux, J.C. Effects of steam sterilization on thermogelling chitosan-based gels. J. Biomed. Mater. Res. 2001, 58, 127-135.
70. Toffey, A.; Samaranayake, G.; Frazier, C.E.; Glasser, W.G. Chitin derivatives. I. Kinetics of the heat-induced conversion of chitosan to chitin. J. Appl. Polym. Sci. 1996, 60, 75-85.
71. Lim, L.Y.; Khor, E.; Ling, C.E. Effects of dry heat and saturated steam on the physical properties of chitosan. J. Biomed. Mater. Res. 1999, 48, 111-116.
72. Yang, Y.M.; Zhao, Y.H.; Liu, X.H.; Ding, F.; Gu, X.S. The effect of different sterilization procedures on chitosan dried powder. J. Appl. Polym. Sci. 2007, 104, 1968-1972.
73. San Juan, A.; Montembault, A.; Gillet, D.; Say, J.P.; Rouif, S.; Bouet, T.; Royaud, I.; David, L. Degradation of chitosan-based materials after different sterilization treatments. IOP Conf. Ser. Mater. Sci. Eng. 2012, 31, 1-5.
74. Lim, L.Y.; Khor, E.; Koo, O. Gamma irradiation of chitosan. J. Biomed. Mater. Res. 1998, 43, 282-290.
75. Jarry C.; Leroux J.C.; Haeck J.; Chaput C. Irradiating or autoclaving chitosan/polyol solutions: Effect on thermogelling chitosan-beta-glycerophosphate systems. Chem. Pharm. Bull. 2002, 50, 1335-1340.
76. Marreco, P.R.; da Luz Moreira, P.; Genari, S.C.; Moraes, A.M. Effects of different sterilization methods on the morphology, mechanical properties, and cytotoxicity of chitosan membranes used as wound dressings. J. Biomed. Mater. Res. B Appl. Biomater. 2004, 71, 268-277.
77. França, R.; Mbeh, D.A.; Samani, T.D.; le Tien, C.; Mateescu, M.A.; Yahia, L.; Sacher, E. The effect of ethylene oxide sterilization on the surface chemistry and in vitro cytotoxicity of several kinds of chitosan. J. Biomed. Mater. Res. B Appl. Biomater. 2013, 101, 1444-1455.
78. No, H.K.; Kim, S.H.; Lee, S.H.; Park, N.Y.; Prinyawiwatkul, W. Stability and antibacterial activity of chitosan solutions affected by storage temperature and time. Carbohydr. Polym. 2006, 65, 174-178.
79. Corazzari, I.; Nisticò, R.; Turci, F.; Faga, M.G.; Franzoso, F.; Tabasso, S.; Magnacca, G. Advanced physico-chemical characterization of chitosan by means of TGA coupled on-line with FTIR and GCMS: Thermal degradation and water adsorption capacity. Polym. Degrad. Stabil. 2015, 112, 1-9.
80. Diab, M.A.; El-Sonbati, A.Z.; Bader, D.M. Thermal stability and degradation of chitosan modified by benzophenone. Spectrochim. Acta A. Mol. Biomol. Spectrosc. 2011, 79, 1057-1062.
81. Pieróg, M.; Ostrowska-Czubenko, J.; Gierszewska-Drużyńska, M. Thermal degradation of double crosslinked hydrogel chitosan mebranes. Progr. Chem. Appl. Chitin Deriv. 2012, 17, 67-74.
82. Zawadzki, J.; Kaczmarek, H. Thermal treatment of chitosan in various conditions. Carbohydr. Polym. 2010, 80, 394-400.
83. Dhawade, P.P.; Jagtap, R.N. Characterization of the glass transition temperature of chitosan and its oligomers by temperature modulated differential scanning calorimetry. Adv. Appl. Sci. Res. 2012, 3, 1372-1382.
84. Prata, A.S.; Grosso, C.R. Production of microparticles with gelatin and chitosan. Carbohydr. Polym. 2015, 116, 292-299.
85. Keegan, G.M.; Smart, J.D.; Ingram, M.J.; Barnes, L.M.; Burnett, G.R.; Rees, G.D. Chitosan microparticles for the controlled delivery of fluoride. J. Dent. 2012, 40, 229-240.
86. Cal, K.; Sollohub, K. Spray drying technique. I: Hardware and process parameters. J. Pharm. Sci. 2010, 99, 575-586.
87. Rampino, A.; Borgogna, M.; Blasi, P.; Bellich, B.; Cesàro, A. Chitosan nanoparticles: Preparation, size evolution and stability. Int. J. Pharm. 2013, 455, 219-228.
88. Yonekura, L.; Sun, H.; Soukoulis, C.; Fisk, I. Microencapsulation of Lactobacillus acidophilus NCIMB 701748 in matrices containing soluble fibre by spray drying: Technological characterization, storage stability and survival after in vitro digestion. J. Funct. Foods 2014, 6, 205-214.
89. Huang, Y.; Yeh, M.; Chiang, C. Formulation factors in preparing BTM-chitosan microspheres by spray drying method. Int. J. Pharm. 2002, 242, 239-242.
90. Aranaz, I.; Gutiérrez, M.C.; Ferrer, M.L.; del Monte, F. Preparation of chitosan nanocomposites with a macroporous structure by unidirectional freezing and subsequent freeze-drying. Mar. Drugs 2014, 12, 5619-5642.
91. Hafner, A.; Dürrigl, M.; Pepić, I.; Filipović-Grčić, J. Short- and long-term stability of lyophilised melatonin-loaded lecithin/chitosan nanoparticles. Chem. Pharm. Bull. 2011, 59, 1117-1123.
92. Abdelwahed, W.; Degobert, G.; Stainmess, S.; Fessi, H. Freeze-drying of nanoparticles Formulation, process and storage considerations. Adv. Drug Deliv. Rev. 2006, 58, 1688-1713.
93. Schuetz, Y.B.; Gurny, R.; Jordan, O. A novel thermoresponsive hydrogel based on chitosan. Eur. J. Pharm. Biopham. 2008, 68, 19-25.
94. Luangtana-Anan, M.; Limmatvapirat, S.; Nunthanid, J.; Chalongsuk, R.; Yamamoto, K. Polyethylene glycol on stability of chitosan microparticulate carrier for protein. AAPS Pharm. Sci. Tech. 2010, 11, 1376-1382.
95. Mao, H.-Q.; Roy, K.; Troung-Le, V.L.; Janes, K.A.; Lin, K.Y.; Wang, Y.; August, J.T.; Leong, K.W. Chitosan-DNA nanoparticles as gene carriers: Synthesis, characterization and transfection efficiency. J. Control. Release 2001, 70, 399-421.
96. Hermans, K.; van den Plas, D.; Kerimova, S.; Carleer, R.; Adriaensens, P.; Weyenberg, W.; Ludwig, A. Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine A. Int. J. Pharm. 2014, 472, 10-19.
97. Wu, D.; Delair, T. Stabilization of chitosan/hyaluronate colloidal polyelectrolyte complexes in physiological conditions. Carbohydr. Polym. 2015, 119, 149-158.
98. Khoo, C.G.; Frantzich, S.; Rosinski, A.; Sjöström, M.; Hoogstraate, J. Oral gingival delivery systems from chitosan blends with hydrophilic polymers. Eur. J. Pharm. Biopharm. 2003, 55, 47-56.
99. El-Hefian, E.A.; Nasef, M.M.; Yahaya, A.H. Chitosan-based polymer blends: Current status and applications. J. Chem. Soc. Pak. 2014, 36, 11-28.
100. Gupta, K.C.; Jabrail, F.H. Glutaraldehyde and glyoxal cross-linked chitosan microspheres for controlled delivery of centchroman. Carbohydr. Res. 2006, 341, 744-756.
101. Li, B.; Shan, C.L.; Zhou, Q.; Fang, Y.; Wang, Y.L.; Xu, F.; Han, L.R.; Ibrahim, M.; Guo, L.B.; Xie, G.L.; et al. Synthesis, characterization, and antibacterial activity of cross-linked chitosan-glutaraldehyde. Mar. Drugs 2013, 11, 1534-1552.
102. Minet, E.P.; O'Carroll, C.; Rooney, D.; Breslin, C.; McCarthy, C.P.; Gallagher, L.; Richards, K.G. Slow delivery of a nitrification inhibitor (dicyandiamide) to soil using a biodegradable hydrogel of chitosan. Chemosphere 2013, 93, 2854-2858.
103. Fernandes, M.; Gonçalves, I.C.; Nardecchia, S.; Amaral, I.F.; Barbosa, M.A.; Martins, M.C. Modulation of stability and mucoadhesive properties of chitosan microspheres for therapeutic gastric application. Int. J. Pharm. 2013, 454, 116-124.
104. Kyzas, G.Z.; Bikiaris, D.N. Recent modifications of chitosan for adsorption applications: A critical and systematic review. Mar. Drugs 2015, 13, 312-337.
105. Liu, C.; Thormann, E.; Claesson, P.M.; Tyrode, E. Surface grafted chitosan gels. Part II. Gel formation and characterization. Langmuir 2014, 30, 8878-8888.
106. Mekhail, M.; Jahan, K.; Tabrizian, M. Genipin-crosslinked chitosan/poly-L-lysine gels promote fibroblast adhesion and proliferation. Carbohydr. Polym. 2014, 108, 91-98.
107. Butler, M.F.; Clark, A.H.; Adams, S. Swelling and mechanical properties of biopolymer hydrogels containing chitosan and bovine serum albumin. Biomacromolecules 2006, 7, 2961-2970.
108. Hamman, J.H. Chitosan Based Polyelectrolyte Complexes as Potential Carrier Materials in Drug Delivery Systems. Mar. Drugs 2010, 8, 1305-1322.
109. Dautzenberg, H.; Kriz, J. Response of polyelectrolyte complexes to subsequent addition of salts with different cations. Langmuir 2003, 19, 5204-5211.
110. Allam, A.N.; Naggar, V.F.; El Gamal, S.S. Formulation and physicochemical characterization of chitosan/acyclovir co-crystals. Pharm. Dev. Technol. 2013, 18, 856-865.
111. Umerska, A.; Paluch, K.J.; Inkielewicz-Stępniak, I.; Santos-Martinez, M.J.; Corrigan, O.I.; Medina, C.; Tajber, L. Exploring the assembly process and properties of novel crosslinker-free hyaluronate-based polyelectrolyte complex nanocarriers. Int. J. Pharm. 2012, 436, 75-87.
112. Mitra, T.; Sailakshmi, G.; Gnanamani, A.; Mandal, A.B. Studies on cross-linking of succinic acid with chitosan/collagen. Materials Res. 2013, 16, 755-765.
113. Ruan, H.; Yu, Y.; Liu, Y.; Ding, X.; Guo, X.; Jiang, Q. Preparation and characteristics of thermoresponsive gel of minocycline hydrochloride and evaluation of its effect on experimental periodontitis models. Drug Deliv. 2014, 25, 1-7.
114. Supper, S.; Anton, N.; Seidel, N.; Riemenschnitter, M.; Schoch, C.; Vandamme, T. Rheological study of chitosan/polyol-phosphate systems: Influence of the polyol part on the thermo-induced gelation mechanism. Langmuir 2013, 29, 10229-10237.
115. Supper, S.; Anton, N.; Seidel, N.; Riemenschnitter, M.; Curdy, C.; Vandamme, T. Thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives in pharmaceutical and biomedical applications. Expert Opin. Drug Deliv. 2014, 11, 249-267.
116. Chenite, A.; Chaput, C.; Wang, D.; Combes, C.; Buschmann, M.D.; Hoemann, C.D.; Leroux, J.C.; Atkinson, B.L.; Binette, F.; Selmani, A. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 2000, 21, 2155-2161.
117. Ruel-Gariépy, E.; Chenite, A.; Chaput, C.; Guirguis, S.; Leroux, J. Characterization of thermosensitive chitosan gels for the sustained delivery of drugs. Int. J. Pharm. 2000, 203, 89-98.
118. Celebi, N.; Ermiş, S.; Ozkan, S. Development of topical hydrogels of terbinafine hydrochloride and evaluation of their antifungal activity. Drug Dev. Ind. Pharm. 2014, doi:10.3109/ 03639045.2014.891129.
119. Murray, C.A.; Dutcher, J.R. Effect of changes in relative humidity and temperature on ultrathin chitosan films. Biomacromolecules 2006, 7, 3460-3465.