N. K. Al-nemrawi, S. S. M. Alsharif, R. H. Dave


Objective: The aim of this work was to prepare chitosan nanoparticles (CS NPs) using sodium tripolyphosphate (TPP) as crosslinker and to study the effect of chitosan polymeric properties and experimental conditions on the properties and stability of NPs.

Methods: CS NPs were prepared by ionic gelation method, using TPP as a crosslinker. The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and the morphologies of the NPs were studied. CS NPs prepared by varying the concentration of TPP, Chitosan molecular weight and its degree of deacetylation, the stirring speed, the rate of TPP addition and the freeze-drying method to study the effect of these variables on the NPs. The stability of the CS NPs was evaluated by storing aqueous suspensions of NPs and comparing the PS, PDI and ZP at the beginning and the end of the experiment.

Results: This study shows that the PS, ZP and dispersity of the NPs depend on the chitosan polymeric properties and experimental conditions. The NPs sizes range between 145.73 and 724.23 nm. They all carried positive charges ranging between+4.32 and+43.67 mV. Most of the NPs have the same sizes after freeze-drying, but showed higher monodispersity and ZP, indicating higher stability. After twenty days of studying the stability, the NPs that had low ZP showed a large increment in size in comparison to the highly charged NPs.

Conclusion: In conclusion, the polymeric properties and formulation variables in the ionic gelation method have a great influence on the CS NPs formed.


Chitosan, TPP, Stability, Nanoparticles

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Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Controlled Release 2004;100:5–28.

Harish Prashanth KV, Tharanathan RN. Chitin/chitosan: modifications and their unlimited application potential-an overview. Trends Food Sci Technol 2007;18:117–31.

Pillai CKS, Paul W, Sharma CP. Chitin and chitosan polymers: chemistry, solubility and fiber formation. Prog Polym Sci 2009;34:641–78.

Fan W, Yan W, Xu Z. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B 2012;90:21–7.

Ilium L. Chitosan and Its use as a pharmaceutical excipient. Pharm Res 1998;15:1326–31.

Campos AM de, Diebold Y, Carvalho ELS. Chitosan nanoparticles as new ocular drug delivery systems: in vitro stability, in vivo fate, and cellular toxicity. Pharm Res 2004;21:803–10.

Dyer AM, Hinchcliffe M, Watts P. Nasal delivery of insulin using novel chitosan-based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 2002;19:998–1008.

Sun Y, Wan A. Preparation of nanoparticles composed of chitosan and its derivatives as delivery systems for macromolecules. J Appl Polym Sci 2007;105:552–61.

Cui F, He C, He M. Preparation and evaluation of chitosan-ethylenediaminetetraacetic acid hydrogel films for the mucoadhesive transbuccal delivery of insulin. J Biomed Mater Res A 2009;89:1063–71.

Chakravarthi SS, Robinson DH. Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles. Int J Pharm 2011;409:111–20.

Thanou M, Florea BI, Geldof M. Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials 2002;23:153–9.

Takeuchi I, Takeshita T, Suzuki T. Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for positively charged drugs. Colloids Surf B 2017;160:520–6.

Varshosaz J, Taymouri S, Hamishehkar H. Fabrication of polymeric nanoparticles of poly(ethylene-co-vinyl acetate) coated with chitosan for pulmonary delivery of carvedilol. J Appl Polym Sci 2014;131.

Wu J, Wang Y, Yang H. Preparation and biological activity studies of resveratrol loaded ionically cross-linked chitosan-TPP nanoparticles. Carbohydr Polym 2017;175:170–7.

Jing ZW, Jia YY, Wan N. Design and evaluation of novel pH-sensitive ureido-conjugated chitosan/TPP nanoparticles targeted to helicobacter pylori. Biomaterials 2016;84:276–85.

Lee E, Park SJ, Lee JH. P-049-preparation of chitosan–TPP nanoparticles and their physical and biological properties. Asian J Pharm Sci 2016;11:166–7.

Kulakovskaya TV, Vagabov VM, Kulaev IS. Inorganic polyphosphate in industry, agriculture and medicine: modern state and outlook. Process Biochem 2012;47:1–10.

Nagpal K, Singh SK, Mishra DN. Optimization of brain-targeted chitosan nanoparticles of rivastigmine for improved efficacy and safety. Int J Biol Macromol 2013;59:72–83.

Qinna NA, Karwi QG, Al-Jbour N. Influence of molecular weight and degree of deacetylation of low molecular weight chitosan on the bioactivity of oral insulin preparations. Mar Drugs 2015;13:1710–25.

Taetz S, Nafee N, Beisner J. The influence of chitosan content in cationic chitosan/PLGA nanoparticles on the delivery efficiency of antisense 2′-O-methyl-RNA directed against telomerase in lung cancer cells. Eur J Pharm Biopharm 2009;72:358–69.

Obaidat R, Al-Jbour N, Al-Sou’d K. Some physicochemical properties of low molecular weight chitosans and their relationship to conformation in aqueous solution. J Solut Chem 2010;39:575–88.

Elsayed A, Remawi MA, Qinna N. Formulation and characterization of an oily-based system for oral delivery of insulin. Eur J Pharm Biopharm 2009;73:269–79.

Qandil AM, Obaidat AA, Ali MAM. Investigation of the interactions in complexes of low molecular weight chitosan with ibuprofen. J Solut Chem 2009;38:695–712.

Manimekalai P, Dhanalakshmi R, Manavalan R. Preparation and characterization of ceftriaxone sodium encapsulated chitosan nanoparticles. Int J Appl Pharm 2017;9:10–5.

Ojha S, Kumar B. Formulation and optimization of chitosan nanoparticles of dimethyl fumarate using box-behnken design. Int J Appl Pharm 2016;8:10–7.

Thandapani G, PSP, PNS. Size optimization and in vitro biocompatibility studies of chitosan nanoparticles. Int J Biol Macromol 2017;104:1794–806.

Retamal Marin RR, Babick F, Hillemann L. Zeta potential measurements for non-spherical colloidal particles–practical issues of characterisation of interfacial properties of nanoparticles. Colloids Surf A 2017;532:516–21.

Choi MJ, Briançon S, Andrieu J. Effect of freeze-drying process conditions on the stability of nanoparticles. Dry Technol 2004;22:335–46.

Abdelwahed W, Degobert G, Stainmesse S. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Delivery Rev 2006;58:1688–713.

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Chitosan, TPP, Stability, Nanoparticles





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International Journal of Applied Pharmaceutics
Vol 10, Issue 5 (Sep-Oct), 2018 Page: 60-65

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Authors & Affiliations

N. K. Al-nemrawi
Department of Pharmaceutical Technology\ Faculty of Pharmacy\ Jordan University of Science and Technology, Irbid 22110-Jordan,

S. S. M. Alsharif
Department of Applied Biological Sciences\ Faculty of Science and Art\ Jordan University of Science and Technology, Irbid-22110-Jordan

R. H. Dave
Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Pharmaceutical Sciences, 75 Dekalb Avenue Brooklyn, NY, USA 11201
United States


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