Abstract
Albendazole is poorly soluble in water and has low bioavailability. The objective of this study was to improve the solubility of albendazole and optimize preparation of an oral nanoparticle formulation, using chitosan-tripolyphosphate (TPP) nanoparticles. The formulation was prepared by mixing the drug solution in Tween 20 with the chitosan solution. TPP solution was added drop wise with sonication to produce a nanoparticle through ionic crosslinking. The dispersion method and TPP loading devices were varied to prepare desirable-sized nanoparticles and subsequently examine drug solubility, nanoparticle size and cytotoxicity. Cytotoxicity of each vehicle was measured by MTT assay. The particle size of blank nanoparticles was 370 nm with a 0.171 polydispersity index when the volume ratio of TPP to chitosan was 1:5. Addition of Tween 20 to solubilize albendazole increased particle size and polydispersity index to 470 nm and 0.251, respectively. The optimized preparation conditions were water bath sonication for 30 min and TPP loading using yellow pipette tips, which produced a small particle size of 235 nm and a polydispersity index of 0.367. Filtration reduced particle size, but increased the polydispersity index. The albendazole-loaded nanoparticles showed higher cytotoxicity than albendazole suspension, even though the chitosan-TPP nanoparticle formulation was itself not toxic. The chitosan-TPP nanoparticles increased the drug solubility and have the potential to deliver albendazole as an anti-cancer agent.
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Anitha A, Deepa N, Chennazhi KP, Nair SV, Tamura H, Jayakumer R (2011) Development of mucoadhesive thiolated chitosan nanoparticles for biomedical applications. Carbohydr Polym 83:66–73
Baldrick P (2010) The safety of chitosan as a pharmaceutical excipient. Regul Toxicol Pharmcol 56:290–299
Barrera MG, Leonardi D, Bolmaro RE, Echenique CG, Olivieri AC, Salomon CJ, Lamas MC (2010) In vivo evaluation of albendazole microspheres for the treatment of Toxocara canis larva migrans. Eur J Pharm Biopharm 75:451–454
Castro SG, Sanchez Bruni SF, Urbizu LP, Confalonieri A, Ceballos L, Lanusse CE, Allemandi DA, Palma SD (2013) Enhanced dissolution and systemic availability of albendazole formulated as solid dispersions. Pharm Dev Technol 18:434–442
Cook GC (1990) Use of benzimidazole chemotherapy in human helminthiases: indication and efficacy. Parasitol Today (Regul Ed). 6:133–136
Dvorožňková E, Hrčková G, Borošková Z, Velebný S, Dubinský P (2004) Effect of treatment with free and liposomized albendazole on selected immunological parameters and cyst growth in mice infected with Echinococcus multilocularis. Parasitol Int 53:315–325
Evrard B, Chiap P, DeTullio P, Ghalmi F, Piel G, Van Hees T, Crommen J, Losson B, Delattre L (2002) Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-beta-cyclodextrin. J Control Release 85:45–50
Fàbregas A, Miñarro M, García-Montoya E, Pérez-Lozano P, Carrillo C, Sarrate R, Sánchez N, Ticó JR, Suñé-Negre JM (2013) Impact of physical parameters on particle size and reaction yield when using the ionic gelation method to obtain cationic polymeric chitosan-tripolyphosphate nanoparticles. Int J Pharm 446:199–204
Gan Q, Wang T, Cochrane C, McCarron P (2005) Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids surf B 44:65–73
García JJ, Bolás F, Torrado JJ (2003) Bioavailability and efficacy characteristics of two different oral liquid formulations of albendazole. Int J Pharm 250:351–358
Gupta BP, Thakur N, Jain NP, Banweer J, Jain S (2010) Osmotically comtrolled drug delivry system with associated drugs. J Pharm Pharm Sci 13:571–588
Harun K, Mistafa M, Alisa S (2013) Effect of particle size on the dissolution of glibenclamide. Int J Pharm Pharm Sci 5:775–779
Jung H, Medina L, García L, Fuentes I, Moreno-Esparza T (1998) Absorption studies of albendazole and some physicochemical properties of the drug and its metabolite albendazole sulphoxide. J Pharm Pharmacol 50:43–48
Liu Y, Wang CQ, Ren WX, Chen YL, Yu Y, Zhang JK, Bawudong D, Gu JP, Xu XD, Zhang XN (2013) Novel albendazole-chitosan nanoparticles for intestinal absorption enhancement and hepatic targeting improvement in rats. J Biomed Mater Res B Appl Biomater 101:998–1005
Morris GA, Castile J, Smith A, Adams GG, Harding SE (2011) The effect of prolonged storage at different temperatures on the particle size distribution of tripolyphosphate (TPP)-chitosan nanoparticles. Carbohyd Polym 84:1430–1434
Nasti A, Zaki NM, De Leonaridis P, Ungphaiboon S, Rimoli MG, Tirelli N (2009) Chitosan/TPP and chitosan/TPP-hyaluronic acid nanoparticles: systematic optimization of the preparative process and preliminary biological evaluation. Pharm Res 26:1918–1930
Shekunov BY, Chattopadhyay P, Tong HHY, Chow AHHL (2007) Particle size analysis in pharmaceutics: principles, methods and applications. Pharm Res 24:203–227
Tsai ML, Bai SW, Chen RH (2008) Cavitation effects versus stretch effects resulted in different size and polydispersity of ionotropic gelation chitosan-sodium tripolyphosphate nanoparticle. Carbohydr Polym 71:448–457
Tsai ML, Chen RH, Bai SW, Chen WY (2011) The storage stability of chitosan/tripolyphosphate nanoparticles in a phosphate buffer. Carbohydr Polym 84:756–761
Vila A, Sánchez A, Tobiĭo M, Calvo P, Alonso MJ (2002) Design of biodegradable particle for protein delivery. J Control Release 78:15–24
Vogt M, Kunath K, Dressman JB (2008) Dissolution improvement of four poorly water soluble drugs by cogrinding with commonly used excipients. Eur J Pharm Biopharm 68:330–337
Zhang H, Oh M, Allen C, Kumacheva E (2004) Monodisperse chitosan nanoparticles for mucosal drug delivery. Biomacromolecules 5:2461–2468
Zhang XN, Gong JH, Tang LH, Zhang Q (2008) Studies on the drug-loading mechanism of polybutylcyanocrylate nanoparticle and its stability of thermodynamics. Curr Nanosci 4:59–61
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This article does not contain any studies with human and animal subjects performed by any of the authors. And all authors (BS Kang, SE Lee, CL Ng, CW Cho and JS Park) declare that they report no conflict of interest. This work was supported by research fund of Chungnam National University in 2014.
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Kang, BS., Lee, SE., Ng, C.L. et al. Determination of preparation parameters for albendazole-loaded nanoparticles using chitosan and tripolyphosphate. Journal of Pharmaceutical Investigation 45, 265–269 (2015). https://doi.org/10.1007/s40005-015-0171-6
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DOI: https://doi.org/10.1007/s40005-015-0171-6