PREPARATION, CHARACTERISATION AND COLLOIDAL STABILITY OF CHITOSAN-TRIPOLYPHOSPHATE NANOPARTICLES: OPTIMISATION OF FORMULATION AND PROCESS PARAMETERS
Objective: Chitosan (CS)â€“tri polyphosphate (TPP)â€“nano particles (NPs) have been extensively studied during the past few decades due to their well-recognized applicability in various fields. Thus, the present study was aimed to optimise the fabrication conditions for the preparation of CS-TPP-NPs aiming towards smallest possible size, optimal zeta potential and narrow poly dispersity index (PDI), simultaneously.
Methods: CS-TPP-NPs were prepared via ionic cross-linking of CS and TPP and were characterized physico-chemically (particle size, zeta potential and PDI) and morphologically. The influence of several formulation conditions (CS concentrations, CS: TPP mass ratio and initial pH of CS solutions) and process parameters (stirring speed, stirring time, ultra-sonication and ultra-centrifugation) on the colloidal characteristics of CS-TPP-NPs were investigated. In addition, the colloidal stability of the prepared NPs was also assessed on storage.
Results: Results clearly identified that the formulation and process parameters showed significant impact on the physico-chemical and morphological characteristics of the CS-TPP-NPs. The CS-TPP-NPs prepared under optimum conditions (CS concentration of 0.2 mg/ml, CS: TPP mass ratio of 7:1, initial pH of CS solution of 4.0, stirred at 700 rpm for 10 min and ultra-centrifuged at 25 000 rpm for 30 min) had shown a mean particle size of ~187Â±21 nm, zeta potential of+37Â±3.5 mV, PDI of ~0.28Â±0.0390 as well as the smooth and round shaped morphology.
Conclusion: The present study describes the optimal circumstances to fabricate the CS-TPP-NPs with finest physico-chemical characteristics and also explore the prospects of manipulation and optimisation of the NPs for intended applications.
Keywords: Chitosan nanoparticles, Ionic cross-linking, Morphology, Ultra-sonication, Ultra-centrifugation, Colloidal stability
Lademann J, Richter H, Teichmann A, Otberg N, Blume-Peytavi U, Luengo J, et al. Nanoparticlesâ€“an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm 2007;66:159â€“64.
Alvarez-Roman R, Barre G, Guy RH, Fessi H. Biodegradable polymer nano capsules containing a sunscreen agent: preparation and photoprotection. Eur J Pharm Biopharm 2001; 52:191â€“5.
Colonna C, Conti B, Perugini P, Pavanetto F, Modena T, Dorati R, et al. Ex vivo evaluation of prolidase loaded chitosan nanoparticles for the enzyme replacement therapy. Eur J Pharm Biopharm 2008;70:58â€“65.
Lee PW, Peng SF, Su CJ, Mi FL, Chen HL, Wei MC, et al. The use of biodegradable polymeric nanoparticles in combination with a low-pressure gene gun for transdermal DNA delivery. Biomaterials 2008;29:742â€“51.
Alvarez-Roman R, Naik A, Kalia YN, Guy RH, Fessi H. Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res 2004;21:1818â€“25.
Kuchler S, Radowski MR, Blaschke T, Dathe M, Plendl J, Haag R, et al. Nanoparticles for skin penetration enhancementâ€“a comparison of a dendritic core-multishell-nano-transporter and solid lipid nanoparticles. Eur J Pharm Biopharm 2009;71:243â€“50.
Wu X, Price GJ, Guy RH. Disposition of nanoparticles and an associated lipophilic permeant following topical application to the skin. Mol Pharmacol 2009;6:1441â€“8.
Katas H, Hussain Z, Ling TC. Chitosan nanoparticles as a percutaneous drug delivery system for hydrocortisone. J Nanomater 2012. Doi: 10.1155/2012/372725. [Article in Press]
Hussain Z, Katas H, Amin MCIM, Kumolosasi E, Buang F, Sahudin S, et al. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model. Int J Pharm 2013;444:109-19.
Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Controlled Release 2004;100:5â€“28.
Zhang H, Oh M, Allen C, Kumacheva E. Monodisperse chitosan nanoparticles for mucosal drug delivery. Biomacromolecules 2004;5:2461â€“8.
Rinaudo M. Chitin and chitosan: properties and applications. Prog Polym Sci 2006;31:603â€“32.
De Moura MR, Aouada FA, Avena-Bustillos RJ, McHugh TH, Krochta JM, Mattoso LH, et al. Improved barrier and mechanical properties of novel hydroxypropylmethyl-cellulose edible films with chitosan/tripolyphosphate nanoparticles. J Food Eng 2009;92:448â€“53.
Gan Q, Wang T, Cochrane C, McCarron P. Modulation of surface charge, particle size and morphological properties of chitosanâ€“TPP nanoparticles intended for gene delivery. Colloids Surf B 2005;44:65â€“73.
Calvo P, RemuËœnÃ¡n-LÃ³pez C, Vila-Jato JL, Alonso MJ. Novel hydrophilic chitosanâ€“polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci 1997;63:125â€“32.
Huang Y, Lapitsky Y. Monovalent salt enhances colloidal stability during the formation of chitosan/tripolyphosphate microgels. Langmuir 2011;27:10392â€“9.
Yang HC, Hon MH. The effect of the degree of deacetylation of chitosan nanoparticles and its characterization and encapsulation efficiency on drug delivery. Polym Plast Technol Eng 2010;49:1292â€“6.
LÃ³pez-LeÃ³n T, Carvalho ELS, Seijo B, Ortega-Vinuesa JL, Bastos-GonzÃ¡lez D. Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behavior. J Colloid Interface Sci 2005;283:344â€“51.
Sinha V, Singla A, Wadhawan S, Kaushik R, Kumria R, Bansal K, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm 2004;274:1â€“33.
Wu Y, Yang W, Wang C, Hu J, Fu S. Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate. Int J Pharm 2005;295:235â€“45.
Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M. Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym 2008;73:44â€“54.
Hussain Z, Katas H, Amin MCIM, Kumulosasi E, Sahudin S. Antidermatitic perspective of hydrocortisone as chitosan nanocarriers: an ex vivo and in vivo assessment using an NC/Nga mouse model. J Pharm Sci 2013;102:1063â€“75.
Grenha A, Seijo B, RemuËœnÃ¡n-LÃ³pez C. Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 2005;25:427â€“37.
Gan Q, Wang T. Chitosan nanoparticle as protein delivery carrierâ€”systematic examination of fabrication conditions for efficient loading and release. Colloids Surf B 2007;59:24â€“34.
Papadimitriou SA, Achilias DS, Bikiaris DN. Chitosan-g-PEG nanoparticles ionically cross-linked with poly(glutamic acid) and tri polyphosphate as protein delivery systems. Int J Pharm 2012;430:318â€“27.
Hu B, Pan C, Sun Y, Hou Z, Ye H, Hu B, et al. Optimization of fabrication parameters to produce chitosanâ€“tripolyphosphate nanoparticles for delivery of tea catechins. J Agric Food Chem 2008;56:7451â€“8.
Luo Y, Zhang B, Cheng WH, Wang Q. Preparation, characterization and evaluation of selenite-loaded chitosan/TPP nanoparticles with or without zein coating. Carbohydr Polym 2010;82:942â€“51.
Keawchaoon L, Yoksan R. Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles. Colloids Surf B 2011;84:163â€“71.
Csaba N, KÃ¶ping-HÃ¶ggÃ¥rd M, Alonso MJ. Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery. Int J Pharm 2009;382:205â€“14.
Floris A, Meloni MC, Lai F, Marongiu F, Maccioni AM, Sinico C, et al. Cavitation effect on chitosan nanoparticle size: a possible approach to protect drugs from ultrasonic stress. Carbohydr Polym 2013;94:619â€“25.
Dai ZZ, Yin JB, Yan SF, Cao T, Ma J, Chen XS, et al. Polyelectrolyte complexes based on chitosan and poly (L-glutamic acid). Polym Int 2007;56:1122â€“7.
Liu H, Gao C. Preparation and properties of ionically cross-linked chitosan nanoparticles. Polym Adv Technol 2009;20:613â€“9.
Fan W, Yan W, Xu Z, Ni H. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B 2012;90:21â€“7.
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;64:29â€“36.
Shu XZ, Zhu KJ. The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release. Eur J Pharm Biopharm 2002;54:235â€“43.
Ko J, Park H, Hwang S, Park J, Lee J. Preparation and characterization of chitosan microparticles intended for controlled drug delivery. Int J Pharm 2002;249:165â€“74.
Sung TL, Fwu LM, Yu JS, Shin SS. Equilibrium and kinetic studies of copper (II) ion uptake by chitosan-tripolyphosphate chelating resin. Polymer 2001;42:1879â€“92.
Zhu HJ, Liu XM, Yangn H, Shen XD. Effect of the stirring rate on physical and electrochemical properties of LiMnPO4 nanoplates prepared in a polyol process. Ceram Interfaces 2014;40:6699â€“704.
Nazeri N, Avadi MR, Faramarzi MA, Safarianc S, Tavoosidana G, Khoshayande MR, et al. Effect of preparation parameters on ultra low molecular weight chitosan/hyaluronic acid nanoparticles. Int J Biol Macromol 2013;62:642â€“6.
Nie KB, Wang XJ, Wu K, Xu L, Zheng MY, Hu XS, et al. Processing, microstructure and mechanical properties of magnesium matrix nanocomposites fabricated by semisolid stirring assisted ultrasonic vibration. J Alloys Compd 2011;509:8664â€“9.
Tang E, Huang M, Lim L. Ultrasonication of chitosan and chitosan nanoparticles. Int J Pharm 2003;265:103â€“14.
Wu YT, Grant CL. Effect of chelation chemistry of sodium polyaspartate on the dissolution of calcite. Chem Biomol Eng 2002;18:6813â€“20.