Eco-friendly synthesis of chitosan and its medical application: from chitin extraction to nanoparticle preparation


  • Riyona Desvy Pratiwi Research Center for Vaccine and Drug, Organization Research of Health, The National Research and Innovation Agency, Jalan Raya Bogor Km 46 Cibinong, Bogor 16911, West Java, Indonesia
  • Sjaikhurrizal El Muttaqien Research Center for Vaccine and Drug, Organization Research of Health, The National Research and Innovation Agency
  • Nunik Gustini Research Center for Vaccine and Drug, Organization Research of Health, The National Research and Innovation Agency
  • Najla Salsabila Difa Research Center for Vaccine and Drug, Organization Research of Health, The National Research and Innovation Agency
  • Gita Syahputra Research Center for Vaccine and Drug, Organization Research of Health, The National Research and Innovation Agency
  • A’liyatur Rosyidah Research Center for Vaccine and Drug, Organization Research of Health, The National Research and Innovation Agency



green synthesis, nano-chitosan, drug delivery
Graphical Abstract


Background and Purpose: Chitosan, a chitin deacetylation product, has been applied in nanoparticle or nano-chitosan for medical applications. However, the chitin extraction from crustacean shells and other natural resources, chitin deacetylation, and crosslinking of the chitosan forming the nano-chitosan mostly involve hazardous chemical and physical processes. The risks of these processes to human health and the environment attract the attention of scientists to develop safer and greener techniques. This review aims to describe the progress of harmless chitosan synthesis. Experimental Approach: All strongly related publications to each section, which were found on scientific search engines (Google Scholar, Scopus, and Pubmed), were studied, selected, and then used as references in writing this review. No limitation for the publication year was applied. The publications were searched from April 2022 - June 2023. Key Results: Nano-chitosan could be synthesized in harmless techniques, including the preparation of the chitosan raw materials and crosslinking the chitosan polymer. Enzymatic processes in shell deproteination in the chitin extraction and deacetylation are preferable to reduce the negative effects of conventional chemical-physical processes. Mild alkalines and deep eutectic solvents also provide similar benefits. In the nano-chitosan synthesis, naturally derived compounds (carrageenan, genipin, and valinin) show potency as safer crosslinkers, besides tripolyphosphate, the most common safe crosslinker. Conclusion: A list of eco-friendly and safer processes in the synthesis of nano-chitosan has been reported in recent years. These findings are suggested for the nano-chitosan synthesis on an industrial scale in the near future.


Download data is not yet available.


M.K. Teli, S. Mutalik, G.K. Rajanikant. Nanotechnology and Nanomedicine: Going Small Means Aiming Big; Current Pharmaceutical Design 16 (2010) 1882-1892.

R. Foulkes, E. Man, J. Thind, S. Yeung, A. Joy, C. Hoskins. The Regulation of Nanomaterials and Nanomedicines for Clinical Application: Current and Future Perspectives. Biomaterial Science 8 (2020) 4653-4664.

H. Peniche, C. Peniche. Chitosan Nanoparticles: A Contribution to Nanomedicine. Polymer International 60 (2011) 883-889.

M.A. Mohammed, J.T.M. Syeda, K.M. Wasan, E.K. Wasan. An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery. Pharmaceutics 9 (2017) 53.

D. Chenthamara, S. Subramaniam, S.G. Ramakrishnan, S. Krishnaswamy, M.M. Essa, F.H. Lin, M.W. Qoronfleh. Therapeutic Efficacy of Nanoparticles and Routes of Administration. Biomaterial Research 23 (2019) 20.

I. Mahapatra, J.R.A. Clark, P.J. Dobson, R. Owen, I. Lynch, J.R. Lead. Expert Perspectives on Potential Environmental Risks from Nanomedicines and Adequacy of the Current Guideline on Environmental Risk Assessment. Environmental Science Nano 5 (2018) 1873-1889.

P. Beaney, J. Lizardi-Mendoza, M. Healy. Comparison of Chitins Produced by Chemical and Bioprocessing Methods. Journal of Chemical Technology and Biotechnology 80 (2005) 145-150.

M. Yanat, K. Schroën. Preparation Methods and Applications of Chitosan Nanoparticles; with an Outlook toward Reinforcement of Biodegradable Packaging. Reactive and Functional Polymer 161 (2021) 104849.

B.T. Iber, N.A. Kasan, D. Torsabo, J.W. Omuwa. A Review of Various Sources of Chitin and Chitosan in Nature. Journal of Renewable Materials 10 (2022) 1097-1123.

G. Crini. Historical Review on Chitin and Chitosan Biopolymers. Environmental Chemistry Letter 17 (2019) 1623-1643.

S.P. Chawla, S.R. Kanatt, A.K. Sharma. Chitosan, in Polysaccharides, K. Ramawat, J.M. Mérillon (Eds)., Springer Cham, 2015, 219-246.

M.V. Tsurkan, A. Voronkina, Y. Khrunyk, M. Wysokowski, M, I. Petrenko, H. Ehrlich. Progress in Chitin Analytics. Carbohydrate Polymers 252 (2021) 117204.

M.A. Hossin, N.H.K. Al Shaqsi, S.J. Al Touby, M.A. Al Sibani. Review of Polymeric Chitin Extraction, Characterization, and Applications. Arabian Journal of Geosciences 14 (2021) 1870.

I. Younes, M. Rinaudo. Chitin and chitosan preparation from marines sources. Structure, properties and applications. Marine Drugs 13 (2015) 1133-1174.

M.N.R. Kumar. A review of chitin and chitosan applications. Reactive and Functional Polymers 46 (2000) 1-27.

M.H. Periayah, A.S. Halim, A.Z.M. Saad. Chitosan: A Promising Marine Polysaccharide for Biomedical Research. Pharmacognosy Review 10 (2016) 39-42.

S. Islam, M.A.R. Bhuiyan, M.N. Islam. Chitin and Chitosan: Structure, Properties and Applications in Biomedical Engineering. Journal of Polymers and The Environment 25 (2017) 854-866.

R. Ravindra, K.R. Krovvidi, A.A. Khan. Solubility Parameter of Chitin and Chitosan. Carbohydrate Polymers 36 (1998) 121-127.

S.B. Nimbeni, B.S. Nimbeni, D.D. Divakar. Role of Chitosan in Remineralization of Enamel and Dentin: A Systematic Review. International Journal of Clinical Pediatric Dentistry 14 (2021) 562-568.

F. Gao, B.S. Zhang, J.H. Zhao, J.F. Huang, P.S. Jia, S. Wang, J. Zhang, J.M. Zhou, H.S. Guo. Deacetylation of Chitin Oligomers Increases Virulence in Soil-Borne Fungal Pathogens. Nature Plants 5 (2019) 1167-1176.

L. Pérez-Álvarez, L. Ruiz-Rubio, J.L. Vilas-Vilela. Determining the Deacetylation Degree of Chitosan: Opportunities to Learn Instrumental Techniques. Journal of Chemical Education 95 (2018) 1022-1028.

O.U. Akakuru, H. Louis, P.I. Amos, O.C. Akakuru, E.I. Nosike, E.F. Ogulewe. The Chemistry of Chitin and Chitosan Justifying Their Nanomedical Utilities. Biochemistry and Pharmacology 7 (2018) 241.

J. Forsythe, G. Rassu, P. Giunchedi, R. James Gilbert, J.C. Mateos-Díaz, D.D. Ojeda-Hernández, D.; A.A. Canales-Aguirre, J. Matias-Guiu, U. Gomez-Pinedo. Potential of Chitosan and Its Derivatives for Biomedical Applications in the Central Nervous System. Frontiers in Bioengineering and Biotechnology 8 (2020) 389.

V.K.Thakur, M.K. Thakur. Recent Advances in Graft Copolymerization and Applications of Chitosan: A Review. ACS Sustainable Chemistry and Engingeering 2 (2014) 2637-2652.

T. Feng, Y. Du, J. Li, Y. Wei, Y.; Yao, P. Antioxidant Activity of Half N-Acetylated Water-Soluble Chitosan in Vitro. European Food Research and Technology 225 (2007) 133-138.

Q.Y. Deng, C.R. Zhou, B.H. Luo. Preparation and Characterization of Chitosan Nanoparticles Containing Lysozyme. Pharmceutical Biology 44 (2006) 336-342.

K. Sweidan, J. Abdel-Motalleb, N.D. Al-Jbour, R.M. Obaidat Jordan. Further investigation on the degree of deacetylation of chitosan determined by potentiometric titration. Journal of Excipients and Food Chemicals 2 (2011) 16-25.

T.A. Khan, K.K. Peh, S.H. Ch’ng. Reporting Degree of Deacetylation Values of Chitosan: The Influence of Analytical Methods. Journal of Pharmacy and Pharmaceutical Science 5 (2002) 205-212.

R. Czechowska-Biskup, D. Jarosińska, B. Rokita, P. Ulański, J.M. Rosiak. Determination of Degree of Deacetylation of Chitosan - Comparison of Methods. Progress on Chemistry and Application of Chitin and Its Derivatives 17 (2012) 5-20. Determination_of_degree_of_deacetylation_of_chitosan_-_Comparision_of_methods

Y. Jiang, C. Fu, S. Wu, G.Liu, J. Guo, Z. Su. Determination of the Deacetylation Degree of Chitooligosaccharides. Marine Drugs 15 (2017) 332.

M. Lavertu, Z. Xia, A.N. Serreqi, M. Berrada, A. Rodrigues, D. Wang, M.D. Buschmann, A. Gupta. A Validated 1H NMR Method for the Determination of the Degree of Deacetylation of Chitosan. Journal of Pharmaceutical and Biomedical Analysis 32 (2003) 1149-1158.

A. Riofrio, T. Alcivar, H. Baykara. Environmental and economic viability of chitosan production in Guayas-Ecuador: a robust investment and life cycle analysis. ACS Omega 6 (2021) 23038-23051.

W. Wang, Y. Du, Y. Qiu, X. Wang, Y. Hu, J. Yang, et al. A new green technology for direct production of low molecular weight chitosan. Carbohydrate polymers 74 (2008) 127-132.

I. Younes, S. Hajj, V. Frachet, M. Rinaudo, K. Jellouli, M. Nasri. Chitin extraction from shrimp shell using enzymatic treatment. Antitumor, antioxidant and antimicrobial activities of chitosan. International Journal of Biological Macromolecules 69 (2014) 489-498.

Y. Yu, X. Liu, J. Miao, K. Leng. Chitin from Antarctic Krill shell: eco-preparation, detection, and characterization. International Journal of Biological Macromolecules 164 (2020) 4125-4137.

H. Zhang, S. Yun, L. Song, Y. Zhang, Y. Zhao. The preparation and characterization of chitin and chitosan under large-scale submerged fermentation level using shrimp by-products as substrate. International Journal of Biological Macromolecules 96 (2017) 334-339.

K. Mohan, A.R. Ganesan, P.N. Ezhilarasi, K.K. Kondamareddy, D.K. Rajan, P. Sathishkumar, J. Rajarajeswaran, L. Conterno. Green and Eco-Friendly Approaches for the Extraction of Chitin and Chitosan: A Review. Carbohydrate Polymers 287 (2022) 119349.

N.S. Mahmoud, A.E. Ghaly, F. Arab. Unconventional approach for demineralization of deproinated crustacean shells for chitin production. American Journal of Biochemistry and Biotechnology 3(1) (2007) 1-9.

A.O. Ameh, M.T. Isa, D. Abutu, A. Danlami. Kinetic modelling of the demineralization of shrimp exoskeleton using citric acid. Leonardo Electron Journal Practice and Technology 25 (2014) 99-108.

I. Younes, O. Ghorbel-Bellaj, R. Nasri, M. Chaabouni, M. Rinaudo, M. Nasri. Chitin and chitosan preparation from shrimp shells using optimized enzymatic deproteinization. Process Biochemistry 47 (2012) 2032-2039.

A.U. Valdez-Peña, J.D. Espinoza-Perez, G.C. Sandoval-Fabian, N. Balagurusamy, A. Hernandez-Rivera, I.M. De-la-Garza-Rodriguez, J.C. Contreras-Esquivel, Screening of industrial enzymes for deproitenization of shrimp head for chitin reco¬very. Food Science and Biotechnology 19 (2010) 553-557.

C. Hongkulsup, V.V. Khutoryanskiy, K. Niranjan. Enzyme assisted extraction of chitin from shrimp shells (Litopenaeus vannamei). Journal of Chemical Technology & Biotechnology 91 (2016) 1250-1256.

M.N. Marzieh, F. Zahra, E. Tahereh, K.N. Sara. Comparison of the physicochemical and structural characteristics of enzymatic produced chitin and commercial chitin. International Journal of Biological Macromolecules 139 (2019) 270-276.

M. Hossain, A. Iqbal. Production and Characterization of Chitosan from Shrimp Waste. Journal of the Bangladesh Agricultural University 12 (2014) 153-160.

C.T.G.V.M.T. Pires, J.A.P Vilela, C. Airoldi. The Effect of Chitin Alkaline Deacetylation at Different Condition on Particle Properties. Procedia Chemistry 9 (2014) 220-225.

R.F. Weska, J.M. Moura, L.M. Batista, J. Rizzi, L.A.A. Pinto. Optimization of Deacetylation in the Production of Chitosan from Shrimp Wastes: Use of Response Surface Methodology. Journal of Food Engineering 80 (2007) 749-753.

G. Galed, E. Diaz, F.M. Goycoolea, A. Heras. Influence of N-Deacetylation Conditions on Chitosan Production from α-Chitin. Natural Product Communications 3 (2008) 543-550.

V.Y. Novikov, I.N. Konovalova, N. Dolgopyatova, N. The Mechanisms of Chitin and Chitosan Deacetylation During Long-term Alkaline Treatment. Applied Biochemsitry and Microbiology 58 (2022) 273-279.

J. Santoso, K.C. Adiputra, L.C. Soerdirga, K. Tarman. Effect of Acetic Acid Hydrolysis on the Characteristics of Water-Soluble Chitosan. In Proceedings of the IOP Conference Series: Earth and Environmental Science 414 (2020) 012021.

C. Casadidio, D.V. Peregrina, M.R. Gigliobianco, S. Deng, R. Censi, P. di Martino. Chitin and Chitosans: Characteristics, Eco-Friendly Processes, and Applications in Cosmetic Science. Marine Drugs 17 (2019) 369.

M.K. Rasweefali, S. Sabu, K.V. Sunooj, A. Sasidharan, K.A.M. Xavier. Consequences of Chemical Deacetylation on Physicochemical, Structural and Functional Characteristics of Chitosan Extracted from Deep-Sea Mud Shrimp. Carbohydrate Polymer Technologies and Applications 2 (2021) 100032.

G.M. Pawaskar, S. Pangannaya, K. Raval, D.R. Trivedi, R. Raval. Screening of Chitin Deacetylase Producing Microbes from Marine Source Using a Novel Receptor on Agar Plate. International Journal of Biology Macromolecular 131 (2019) 716-720.

J. Sebastian, T. Rouissi, S.K. Brar. Fungal Chitosan: Prospects and Challenges. Handbook of Chitin and Chitosan Preparation and Properties 1 (2020) 419-452.

I.A. Hoell, G. Vaaje-Kolstad, V.G.H. Eijsink. Structure and Function of Enzymes Acting on Chitin and Chitosan. Biotechnology Genetic Engineering Review 27 (2010) 331-366.

S. Bartnicki-Garcia’, W.J. Nickerson. Nutrition, Growth, and Morphogenesis of Mucor rouxii. Journal of Bacteriology 84 (1962) 841-867.

D. Kafetzopoulos, A. Martinou, V. Bouriotis. Bioconversion of Chitin to Chitosan: Purification and Characterization of Chitin Deacetylase from Mucor rouxii. Proceedings of the National Academy of Sciences of the United States of America 90 (1993) 2564-2568.

M.B. Kaczmarek, K. Struszczyk-Swita, X. Li, M. Szczęsna-Antczak, Daroch, M. Enzymatic Modifications of Chitin, Chitosan, and Chitooligosaccharides. Frontiers Bioengineering and Biotechnolology 7 (2019) 243.

L. Grifoll-Romero, S. Pascual, H. Aragunde, X. Biarnés, A. Planas. Chitin Deacetylases: Structures, Specificities, and Biotech Applications. Polymers 10 (2018) 352.

K. Tokuyasu, S. Kaneko, K. Hayashi, Y. Mori. Production of a Recombinant Chitin Deacetylase in the Culture Medium of Escherichia coli Cells. FEBS Letters 458 (1999) 23-26.

P. Bhat, G.M. Pawaskar, R. Raval, S. Cord-Landwehr, B. Moerschbacher, B.Raval, K. Expression of Bacillus Licheniformis Chitin Deacetylase in E. coli PLysS: Sustainable Production, Purification and Characterisation. International Journal of Biolology Macromolecule 131 (2019) 1008-1013.

S. Naqvi, S. Cord-Landwehr, R. Singh, F. Bernard, S. Kolkenbrock, N.E. Gueddari, B.M. Moerschbacher. A Recombinant Fungal Chitin Deacetylase Produces Fully Defined Chitosan Oligomers with Novel Patterns of Acetylation. Applied Environmental Microbiology 82 (2016) 6645-6655.

B. Shrestha, K. Blondeau, W.F. Stevens, F.L. Hegarat. Expression of Chitin Deacetylase from Colletotrichum Lindemuthianum in Pichia pastoris: Purification and Characterization. Protein Expression and Purification 38 (2004) 196-204.

C. Mishra, C.E. Semino, K.J. Mccreath, H. de La Vega, B.J. Jones, C.A. Specht, P.W. Robbins. Cloning and Expression of Two Chitin Deacetylase Genes of Saccharomyces cerevisiae. Yeast 13 (1997) 327-336.

M.B. Kaczmarek, K. Struszczyk-Swita, M. Xiao, M. Szczęsna-Antczak, T. Antczak, M. Gierszewska, A. Steinbüchel, M. Daroch. Polycistronic Expression System for Pichia pastoris Composed of Chitino- and Chitosanolytic Enzymes. Frontiers Bioengineering and Biotechnolology 9 (2021) 710922.

A. Martinou, D. Koutsioulis, V. Bouriotis. Cloning and Expression of a Chitin Deacetylase Gene (CDA2) from Saccharomyces cerevisiae in Escherichia coli: Purification and Characterization of the Cobalt-Dependent Recombinant Enzyme. Enzyme Microbiology Technology 32 (2003) 757-763.

H. el Knidri, J. Dahmani, A. Addaou, A. Laajeb, A. Lahsini. Rapid and Efficient Extraction of Chitin and Chitosan for Scale-up Production: Effect of Process Parameters on Deacetylation Degree and Molecular Weight. International Journal of Biological Macromolecules 139 (2019) 1092-1102.

A. Zaeni, E. Safitri, B. Fuadah, I.N. Sudiana. Microwave-assisted hydrolysis of chitosan from shrimp shell waster for glucosamine hydrochlorid production. The 5th International Conference on Theoretical and Applied Physics, IOP Publishing of Physics Conference Series. 846 (2015) 23-25.

J. Zhang, M. Feng, X. Lu, C. Shi, X. Li, J. Xin, et al. Base-free preparation of low molecular weight chitin from crab shell. Carbohydrate Polymers 190 (2018) 148-155.

S. Tsubaki, J.I. Azuma. Total fractional of green tea residue by microwave-assisted alkaline pretreatment and enzymatic hydrolysis. Biosensor Technology. 131 (2013) 485-491.

F. Li, X. You, Q. Li, D. Qin, M. Wang, S. Yuan, X. Chen, S. Bi. Homogeneous Deacetylation and Degradation of Chitin in NaOH/Urea Dissolution System. International Journal of Biological Macromolecules 189 (2021) 391-397.

F.A. Vicente, M. Huš, B. Likozar, U. Novak. Chitin Deacetylation Using Deep Eutectic Solvents: Ab Initio-Supported Process Optimization. ACS Sustainable Chemical Engineering 9 (2021) 3874-3886,

E.L. Smith, A.P. Abbott, K.S. Ryder. Deep Eutectic Solvents (DESs) and Their Applications. Chemical Reviews 114 (2014) 11060-11082.

D. Zhao, W.C. Huang, N. Guo, S. Zhang, C. Xue, X. Mao. Two-Step Separation of Chitin from Shrimp Shells Using Citric Acid and Deep Eutectic Solvents with the Assistance of Microwave. Polymers 11 (2019) 409.

S.A. White, R. Farina-Peter, I. Fulton. Production and Isolation of Chitosan from Mucor rouxii. Applied and Environmental Microbiology 38 (1979) 323-326.

H. Zhang, H. Tachikawa, X.D. Gao, H. Nakanishi. Applied Usage of Yeast Spores as Chitosan Beads. Applied and Environmental Microbiology 80 (2014) 5098-5105.

M. Afroz, M. Nayeem, H. Kashem, M. Masirul Afroz, N.H. Kashem, K.M. Prottoy, S. Piash, N. Islam. Saccharomyces Cerevisiae as an Untapped Source of Fungal Chitosan for Antimicrobial Action. Applied Biochemistry and Biotechnology 193 (2021) 3765–3786.

N. Morin-Crini, E. Lichtfouse, G. Torri, G. Crini. Applications of Chitosan in Food, Pharmaceuticals, Medicine, Cosmetics, Agriculture, Textiles, Pulp and Paper, Biotechnology, and Environmental Chemistry. Environmental Chemistry Letters 17 (2019) 1667-1692.

Z. Shariatinia. Pharmaceutical Applications of Chitosan. Advanced Colloid Interface Science 263 (2019) 131-194.

S. Bayda, M. Adeel, T. Tuccinardi, M. Cordani, F. Rizzolio, A. Baeza. Molecules The History of Nanoscience and Nanotechnology: From Chemical-Physical Applications to Nanomedicine. Molecules 25 (2020) 112.

R.A. Freitas. What Is Nanomedicine? Nanomedicine 1 (2005) 2-9.

B. Pelaz, C. Alexiou, R.A. Alvarez-Puebla, F. Alves, A.M. Andrews, Φ.S. Ashraf, L.P. Balogh, L. Ballerini, A. Bestetti, C. Brendel. Diverse Applications of Nanomedicine Nano Focus. ACS Nano 11 (2017) 2313-2381.

J. Morais Catita, B. Salas Valdez, R. Jorge, C. Vitorino, S. Soares, J. Sousa, A. Pais. Nanomedicine: Principles, Properties, and Regulatory Issues. Frontiers in Chemistry 1 (2018) 360.

P. Satalkar, B.S. Elger, D.M.Shaw. Defining Nano, Nanotechnology and Nanomedicine: Why Should It Matter? Science Engineering Ethics 22 (2016) 1255-1276.

D. Astruc, Introduction to Nanomedicine. Molecules 21(1) (2016) 4.

H. Kobayashi, R. Watanabe, P.L. Choyke. Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target? Theranostics 4 (2014) 81-89.

M. Germain, F. Caputo, S. Metcalfe, G. Tosi, K. Spring, A.K.O. Åslund, A. Pottier, R. Schiffelers, A. Ceccaldi, R. Schmid. Delivering the Power of Nanomedicine to Patients Today. Journal of Controlled Release 326 (2020) 164-171.

P. Ray, N. Haideri, I. Haque, O. Mohammed, S. Chakraborty, S. Banerjee, M. Quadir, A.E. Brinker, S.K. Banerjee. The Impact of Nanoparticles on the Immune System: A Gray Zone of Nanomedicine. The Journal of Immunological Science 5 (2021) 19-33.

D. Zhao, S. Yu, B. Sun, S. Gao, S. Guo, K. Zhao. Biomedical Applications of Chitosan and Its Derivative Nanoparticles. Polymers (Basel) 10 (2018) 462.

E.F. Ribeiro, T.T. de Barros-Alexandrino, O.B.G. Assis, A.C. Junior, A. Quiles, I. Hernando, V.R. Nicoletti. Chitosan and Crosslinked Chitosan Nanoparticles: Synthesis, Characterization and Their Role as Pickering Emulsifiers. Carbohydrate Polymers 250 (2020) 116878.

O.A.C. Monteiro, C. Airoldi. Some Studies of Crosslinking Chitosan-Glutaraldehyde Interaction in a Homogeneous System. International Journal of Biological Macromolecules 26 (1999) 119-128.

N.R. Kildeeva, P.A. Perminov, L. Vladimirov, V. Novikov, S.N. Mikhailov. About Mechanism of Chitosan Cross-Linking with Glutaraldehyde. Russian Journal of Bioorganic Chemsitry 35 (2009) 360-369.

K. Song, H. Xu, B. Mu, K. Xie, Y. Yang. Non-Toxic and Clean Crosslinking System for Protein Materials: Effect of Extenders on Crosslinking Performance. Journal of Cleaner Production 150 (2017) 214-223.

T. Takigawa, Y. Endo. Effects of Glutaraldehyde Exposure on Human Health. Journal of Occupational Health 48 (2006) 75-87.

Y. Zhu, L.M. Marin, Y. Xiao, E.R. Gillies, W.L. Siqueira. pH-Sensitive Chitosan Nanoparticles for Salivary Protein Delivery. Nanomaterials 11 (2021) 1028.

L. Li, G. Jiang, W. Yu, D. Liu, H. Chen, Y. Liu, Z. Tong, X. Kong, J. Yao. Preparation of Chitosan-Based Multifunctional Nanocarriers Overcoming Multiple Barriers for Oral Delivery of Insulin. Materials Science and Engineering: C 70 (2017) 278-286.

L. Li, L. Yang, M. Li, L. Zhang. A Cell-Penetrating Peptide Mediated Chitosan Nanocarriers for Improving Intestinal Insulin Delivery. Carbohydrate Polymers 174 (2017) 182-189.

P. Batista, P. Castro, A.R. Madureira, B. Sarmento, M. Pintado. Development and Characterization of Chitosan Microparticles-in-Films for Buccal Delivery of Bioactive Peptides. Pharmaceutics 12 (2019) 32.

Y. Lv, J. Zhang, C. Wang. Self-Assembled Chitosan Nanoparticles for Intranasal Delivery of Recombinant Protein Interleukin-17 Receptor C (IL-17RC): Preparation and Evaluation in Asthma Mice. Bioengineered 12 (2021) 3029-3039.

M. Zohri, H.A. Javar, T. Gazori, M.R. Khoshayand, S. Hamid Aghaee-Bakhtiari, M.H. Ghahremani. Response Surface Methodology for Statistical Optimization of Chitosan/Alginate Nanoparticles as a Vehicle for Recombinant Human Bone Morphogenetic Protein-2 Delivery. International Journal of Nanomedicine 15 (2020) 8345-8356.

R. Ghosh, A.B. Susmita Mondal, D. Mukherjee, A. Adhikari, S.A. Ahmed, C.D.I. Reem Alsantali, A.S. Khder, C.F.M. Hatem Altass, Z. Moussa, R. Das, et al. Oral Drug Delivery Using a Polymeric Nanocarrier: Chitosan Nanoparticles in the Delivery of Rifampicin. Materials Advances 3 (2022), 4622-4628.

N. Hosseini-Ashtiani, A. Tadjarodi, R. Zare-Dorabei. Low Molecular Weight Chitosan-Cyanocobalamin Nanoparticles for Controlled Delivery of Ciprofloxacin: Preparation and Evaluation. International Journal of Biological Macromolecules 176 (2021) 459-467.

E. Mazzotta, S. de Benedittis, A. Qualtieri, R. Muzzalupo. Pharmaceutics Actively Targeted and Redox Responsive Delivery of Anticancer Drug by Chitosan Nanoparticles. Pharmaceutics 12 (2020) 26.

G. Khairnar, V. Mokale, A. Mujumdar, J. Naik. Development of Nanoparticulate Sustained Release Oral Drug Delivery System for the Antihyperglycemic with Antihypertensive Drug. Materials Technology 34 (2019) 880-888.

N. Aminu, S.Y. Chan, M.F. Yam, S.M. Toh. A Dual-Action Chitosan-Based Nanogel System of Triclosan and Flurbiprofen for Localised Treatment of Periodontitis. International Journal of Pharmacy 570 (2019) 118659.

A.S. Tzeyung, S.K. Bhattamisra, T. Madheswaran, N.A. Alhakamy, H.M. Aldawsari, A.K. Radhakrishnan. Pharmaceutics Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery. Pharmaceutics 11 (2019) 26.

G.N. Shi, C.N Zhang, R. Xu, J.F. Niu, H.J. Song, X.Y. Zhang, W.W. Wang,Y.M. Wang, C. Li, X.Q. Wei. et al. Enhanced Antitumor Immunity by Targeting Dendritic Cells with Tumor Cell Lysate-Loaded Chitosan Nanoparticles Vaccine. Biomaterials 113 (2017) 191-202.

P.D. Lopes, C.H. Okino, F.S. Fernando, C. Pavani, V.M. Casagrande, R.F.V. Lopez, M. Montassier, H.J. Montassier. Inactivated Infectious Bronchitis Virus Vaccine Encapsulated in Chitosan Nanoparticles Induces Mucosal Immune Responses and Effective Protection against Challenge. Vaccine 36 (2018) 2630-2636.

N.H. AbdelAllah, Y. Gaber, M.E. Rashed, A.F. Azmy, H.A. Abou-Taleb, S. AbdelGhani. Alginate-Coated Chitosan Nanoparticles Act as Effective Adjuvant for Hepatitis A Vaccine in Mice. International Journal of Biological Macromolecules 152 (2020) 904-912.

M. Mehrabi, N.M. Dounighi, S.M.R. Sorkhabadi, D. Doroud, A. Amani, M. Khoobi, S. Ajdary, Y. Pilehvar-Soltanahmadi. Development and Physicochemical, Toxicity and Immunogenicity Assessments of Recombinant Hepatitis B Surface Antigen (RHBsAg) Entrapped in Chitosan and Mannosylated Chitosan Nanoparticles: As a Novel Vaccine Delivery System and Adjuvant. Artificial Cells Nanomedine and Biotechnology 46 (2018) 230-240.

S. Zhang, S. Huang, L. Lu, X. Song, P. Li, F. Wang. Curdlan Sulfate-O-Linked Quaternized Chitosan Nanoparticles: Potential Adjuvants to Improve the Immunogenicity of Exogenous Antigens via Intranasal Vaccination. International Journal of Nanomedicine 13 (2018) 2377-2394. 13 2377-2394

J. Zhang, H. Sun, C. Gao, Y. Wang, X. Cheng, Y. Yang, Q. Gou, L. Lei, Y. Chen, X. Wang, et al. Development of a Chitosan‐modified PLGA Nanoparticle Vaccine for Protection against Escherichia coli K1 Caused Meningitis in Mice. Journal of Nanobiotechnology 19 (2021) 69.

C. Rodolfo, D. Eusébio, C. Ventura, R. Nunes, H.F. Florindo, D. Costa, A. Sousa, J. Valente, A. Panitch. Pharmaceutics Design of Experiments to Achieve an Efficient Chitosan-Based DNA Vaccine Delivery System. Pharmaceuitics 13 (2021) 1369.

B.H.G. Marandi, M.R. Zolfaghari, R. Kazemi, M.J. Motamedi, J. Amani. Immunization against Vibrio Cholerae, ETEC, and EHEC with Chitosan Nanoparticle Containing LSC Chimeric Protein. Microbial Pathogenesis 134 (2019) 103600.

M. Bagheri, M. Validi, A. Gholipour, P. Makvandi, E. Sharifi. Chitosan Nanofiber Biocomposites for Potential Wound Healing Applications: Antioxidant Activity with Synergic Antibacterial Effect. Bioengineering and Translational Medicine 7 (2021) 10254.

P. Abrica-González, A. Zamora-Justo, A. Sotelo-López, G.R. Vázquez-Martínez, J.A. Balderas-López, A. Muñoz-Diosdado, M. Ibáñez-Hernández. Gold Nanoparticles with Chitosan, N-Acylated Chitosan, and Chitosan Oligosaccharide as DNA Carriers. Nanoscale Research Letters 14 (2019) 258.

Y.J. Zhang, B. Gao, X.W. Liu. Topical and Effective Hemostatic Medicines in the Battlefield. International Journal of Clinical Experimental Medicine 8 (2015) 10-19.

S. Hu, S. Bi, D. Yan, Z. Zhou, G. Sun, X. Cheng, X. Chen. Preparation of Composite Hydroxybutyl Chitosan Sponge and Its Role in Promoting Wound Healing. Carbohydrate Polymers 184 (2018) 154-163.

C. Cui, S. Sun, S. Wu, S. Chen, J. Ma, F. Zhou. Electrospun Chitosan Nanofibers for Wound Healing Application. Engineered Regeneration 2 (2021) 82-90.

X. Du, L. Wu, H. Yan, Z. Jiang, S. Li, W. Li, Y. Bai, Wang, Z. Cheng, D. Kong, et al. Microchannelled Alkylated Chitosan Sponge to Treat Noncompressible Hemorrhages and Facilitate Wound Healing. Nature Communication 12 (2021) 4733.

J. Chi, X. Zhang, C. Chen, C. Shao, Y. Zhao, Y. Wang. Antibacterial and Angiogenic Chitosan Microneedle Array Patch for Promoting Wound Healing. Bioactive Materials 5 (2020) 253-259,

K.S. Venkataprasanna, J. Prakash, S. Vignesh, G. Bharath, M. Venkatesan, F. Banat, S. Sahabudeen, S. Ramachandran, G.D. Venkatasubbu. Fabrication of Chitosan/PVA/GO/CuO Patch for Potential Wound Healing Application. International Journal of Biological Macromolecules 143 (2020) 744-762.

N. Devi, J. Dutta. Preparation and Characterization of Chitosan-Bentonite Nanocomposite Films for Wound Healing Application. International Journal of Biological Macromolecules 104 (2017) 1897-1904.

A.M. Abdel-Mohsen, J. Frankova, R.M. Abdel-Rahman, A.A. Salem, N.M. Sahffie, I. Kubena, J. Jancar. Chitosan-Glucan Complex Hollow Fibers Reinforced Collagen Wound Dressing Embedded with Aloe Vera. II. Multifunctional Properties to Promote Cutaneous Wound Healing. International Journal of Pharmacy 582 (2020) 119349.

N. Bölgen, D. Demir, M.S. Yalçın, S. Özdemir. Development of Hypericum Perforatum Oil Incorporated Antimicrobial and Antioxidant Chitosan Cryogel as a Wound Dressing Material. International Journal of Biological Macromolecules 161 (2020) 1581-1590.

I. Koumentakou, Z. Terzopoulou, A. Michopoulou, I. Kalafatakis, K. Theodorakis, D. Tzetzis, D. Bikiaris. Chitosan Dressings Containing Inorganic Additives and Levofloxacin as Potential Wound Care Products with Enhanced Hemostatic Properties. International Journal of Biological Macromolecules 162 (2020) 693-703.

J. Si, Y. Yang, X. Xing, F. Yang, P. Shan. Controlled Degradable Chitosan/Collagen Composite Scaffolds for Application in Nerve Tissue Regeneration. Polymer Degradation and Stability 166 (2019) 73-85.

A. Fathi, M. Khanmohammadi, A. Goodarzi, L. Foroutani, Z.T. Mobarakeh, J. Saremi, Z. Arabpour, J. Ai. Fabrication of Chitosan-Polyvinyl Alcohol and Silk Electrospun Fiber Seeded with Differentiated Keratinocyte for Skin Tissue Regeneration in Animal Wound Model. Journal of Biological Engineering 14 (2020) 27.

S. Dasgupta, K. Maji, S.K. Nandi. Investigating the Mechanical, Physiochemical and Osteogenic Properties in Gelatin-Chitosan-Bioactive Nanoceramic Composite Scaffolds for Bone Tissue Regeneration: In Vitro and in Vivo. Materials Science and Engineering C 94 (2019) 713-728.

B.N. Singh, V. Veeresh, S.P. Mallick, Y. Jain, S. Sinha, A. Rastogi, P. Srivastava. Design and Evaluation of Chitosan/Chondroitin Sulfate/Nano-Bioglass Based Composite Scaffold for Bone Tissue Engineering. International Journal of Biological Macromolecules 133 (2019) 817-830.

S.P. Mallick, B.N. Singh, A. Rastogi, P. Srivastava. Design and Evaluation of Chitosan/Poly(l-Lactide)/Pectin Based Composite Scaffolds for Cartilage Tissue Regeneration. International Journal Biological Macromolecules 112 (2018) 909-920.

A.M. dos Santos, S.G. Carvalho, L.M.B. Ferreira, M. Chorilli, M.P.D. Gremião. Understanding the Role of Electrostatic Interactions on the Association of 5-Fluorouracil to Chitosan-TPP Nanoparticles. Colloids Surface A Physicochemical Engingeering Aspects 640 (2022) 128417.

M.F. Warsito, F.A. Agustiani. A Review on Factors Affecting Chitosan Nanoparticles Formation. International Symposium on Applied Chemistry, IOP Conference Series: Materials Science and Engineering, Indonesia, 2020, 012027.

S. Hajji, N. Ktari, R. Ben Salah, S. Boufi, F. Debeaufort, M. Nasri. Development of Nanocomposite Films Based on Chitosan and Gelatin Loaded with Chitosan-Tripolyphosphate Nanoparticles: Antioxidant Potentials and Applications in Wound Healing. Journal of Polymers and the Environment 30 (2022) 833-854.

J.M.N.A. Bezerra, A.C.J. Oliveira, E.C. Silva-Filho, P. Severino, S.B. Souto, E.B. Souto, M.F.L.R Soares, J.L. Soares-Sobrinho. The Potential Role of Polyelectrolyte Complex Nanoparticles Based on Cashew Gum, Tripolyphosphate and Chitosan for the Loading of Insulin. Diabetology 2 (2021) 107-116.

H.C. Yew, M. Misran. Preparation and Characterization of pH Dependent κ-Carrageenan-Chitosan Nanoparticle as Potential Slow Released Delivery Carrier. Iranian Polymer Journal (English Edition) 25 (2016) 1037-1046.

C. Li, S. Hein, K. Wang. Chitosan-Carrageenan Polyelectrolyte Complex for the Delivery of Protein Drugs. ISRN Biomaterials 2013 (2013) 629807.

N.T.N. Vo, L. Huang, H. Lemos, A.L. Mellor, K. Novakovic. Genipin-Crosslinked Chitosan Hydrogels: Preliminary Evaluation of the in Vitro Biocompatibility and Biodegradation. Journal of Applied Polymer Science 138 (2021) 50848.

M.A. Razi, R. Wakabayashi, Y. Tahara, M. Goto, N. Kamiya. Genipin-Stabilized Caseinatehitosan Nanoparticles for Enhanced Stability and Anti-Cancer Activity of Curcumin. Colloids Surface B Biointerfaces 164 (2018) 308-315.

C. Huang, H. Liao, X. Liu, M. Xiao, S. Liao, S. Gong, F. Yang, X. Shu, X. Zhou. Preparation and Characterization of Vanillin-Chitosan Schiff Base Zinc Complex for a Novel Zn2+ Sustained Released System. International Journal of Biological Macromolecules 194 (2022) 611-618.

P.W. Li, G. Wang, Z.M. Yang, W. Duan, Z. Peng, L.X. Kong, Q.H. Wang. Development of Drug-Loaded Chitosan-Vanillin Nanoparticles and Its Cytotoxicity against HT-29 Cells. Drug Delivery 23 (2016) 30-35.

G.A. De Ruiter, Rudolph Brian. Carrageenan Biotechnology. Trends in Food Science & Technology 8 (1997) 389-395.

E.M. Pacheco-Quito, R. Ruiz-Caro, M.D. Veiga. Carrageenan: Drug Delivery Systems and Other Biomedical Applications. Marine Drugs 18 (2020) 583.

V.N. Davydova, I.V. Sorokina, A.V. Volod’ko, E.V. Sokolova, M.S. Borisova, I.M. Yermak. The Comparative Immunotropic Activity of Carrageenan, Chitosan and Their Complexes. Marine Drugs 18 (2020) 458.

T. Khaliq, M. Sohail, M.U. Minhas, S.A. Shah, N. Jabeen, S. Khan, Z. Hussain, A. Mahmood, M. Kousar, H. Rashid. Self-Crosslinked Chitosan/κ-Carrageenan-Based Biomimetic Membranes to Combat Diabetic Burn Wound Infections. International Journal of Biological Macromolecules 197 (2022) 157-168.

S. Rochín-Wong, A. Rosas-Durazo, P. Zavala-Rivera, A. Maldonado, M.E. Martínez-Barbosa, I. Vélaz,J. Tánori. Drug Release Properties of Diflunisal from Layer-by- Layer Self-Assembled k-Carrageenan/Chitosan Nanocapsules: Effect of Deposited Layers. Polymers (Basel) 10 (2018) 760.

T.H. Nguyen, T.C. Nguyen, T.M.T. Nguyen, D.H. Hoang, D.M.T. Tran, D.T. Tran, P.T. Hoang, V.T. Le; T.K.N. Tran, H. Thai. Characteristics and Bioactivities of Carrageenan/Chitosan Microparticles Loading α-Mangostin. Journal of Polymers and the Environmental 30 (2022) 631-643.

N. Wathoni, L. Meylina, A. Rusdin, A.F.A. Mohammed, D. Tirtamie, Y. Herdiana, K. Motoyama, C. Panatarani, I.M. Joni, R. Lesmana, et al. The Potential Cytotoxic Activity Enhancement of α-Mangostin in Chitosan-Kappa Carrageenan-Loaded Nanoparticle against Mcf-7 Cell Line. Polymers (Basel) 13 (2021) 1681.

A.M. Ramos-de-la-Peña, C.M.G.C. Renard, J. Montañez, M. de la Luz Reyes-Vega, J.C. Contreras-Esquivel. A Review through Recovery, Purification and Identification of Genipin. Phytochemistry Reviews 15 (2016) 37-49.

C. Pizzolitto, M. Cok, F. Asaro, F. Scognamiglio, E. Marsich, F. Lopez, I. Donati, P. Sacco. On the Mechanism of Genipin Binding to Primary Amines in Lactose-Modified Chitosan at Neutral pH. International Journal of Molecular Science 21 (2020) 6831.

R.A.A. Muzzarelli. Genipin-Crosslinked Chitosan Hydrogels as Biomedical and Pharmaceutical Aids. Carbohydrate Polymers 77 (2009) 1-9.

A.M. Heimbuck, T.R. Priddy-Arrington, M.L. Padgett, C.B. Llamas, H.H. Barnett, B.A. Bun nell, M.E. Caldorera-Moore. Development of Responsive Chitosan-Genipin Hydrogels for the Treatment of Wounds. ACS Applied Bio Materials 2 (2019) 2879-2888.

Z. Wang, H. Liu, W. Luo, T. Cai, Z. Li, Y. Liu, W. Gao, Q. Wan, et al. Regeneration of Skeletal System with Genipin Crosslinked Biomaterials. Journal of Tissue Engineering 11 (2020) 1-24.

V. Paul, D.C. Rai, R.L. Ramyaa, S.K. Srivastava, A.D. Tripathi. A Comprehensive Review on Vanillin: Its Microbial Synthesis, Isolation and Recovery. Food Biotechnology 35 (2021) 22-49.

D.F. Taber, S. Patel, T.M. Hambleton, E.E. Winkel. Vanillin Synthesis from 4-Hydroxybenzaldehyde. Journal of Chemical Education 84 (2007) 1158.

A.C. Alavarse, E.C.G. Frachini, R.L.C.G. da Silva, V.H. Lima, A. Shavandi, D.F.S. Petri. Crosslinkers for Polysaccharides and Proteins: Synthesis Conditions, Mechanisms, and Crosslinking Efficiency, a Review. International Journal of Biological Macromolecules 202 (2022) 558-596.

O.V. Kharissova, B.I. Kharisov, C.M.O. González, Y.P. Méndez, I. López. Greener Synthesis of Chemical Compounds and Materials. Royal Society Open Science 6 (2019) 191378.

M. Mishra, M. Sharma, R. Dubey, P. Kumari, V. Ranjan, J. Pandey. Green Synthesis Interventions of Pharmaceutical Industries for Sustainable Development. Current Research in Green and Sustainable Chemistry 4 (2021) 100174.

P. Bradu, A. Biswas, C. Nair, S. Sreevalsakumar, M. Patil, S. Kannampuzha, A.G. Mukherjee, U.R. Wanjari, K. Renu, B. Vellingiri. Recent Advances in Green Technology and Industrial Revolution 4.0 for a Sustainable Future. Environmental Science and Pollution Research (2022).



23-09-2023 — Updated on 23-09-2023

How to Cite

Pratiwi, R. D., El Muttaqien, S., Gustini, N., Difa, N. S., Syahputra, G., & Rosyidah, A. (2023). Eco-friendly synthesis of chitosan and its medical application: from chitin extraction to nanoparticle preparation. ADMET and DMPK, 11(4), 435–455.