Hasan AKBABA, Oğuz BAYRAKTAR, Yücel BAŞPINAR

Encapsulation of paclitaxel in electrosprayed chitosan nanoparticles

Paclitaxel is an anti-cancer drug, used to treat ovarian, breast and non-small-cell lung cancer amongothers. The low aqueous solubility of paclitaxel is a limiting factor for its application. Thus, paclitaxel is solubilized withhelp of surfactants and co-solvents, approved as Taxol®. Unfortunately, serious side effects like life-threateninghypersensitivity reactions and hemo-toxicity are limiting its use. Due to this, alternative formulations of paclitaxel arerequired. Nanoparticles represent an important approach to improve the poor solubility of drugs. In that context,electrospray for the preparation of nanoparticles is a promising approach. Due to these facts it was aimed in this studyto develop and characterize paclitaxel loaded zein nanoparticles with and without the addition of chitosan. For thatpurpose the influence of the preparation parameters like the applied voltage and the flow rate on the characteristicproperties of the particles were investigated step by step. The nanoparticles were characterized by investigating theirparticle size, size distribution, zeta potential, shapes and morphologies with help of dynamic light scattering,encapsulation efficiencies and AFM images, respectively. It was succeeded to prepare paclitaxel loaded zeinnanoparticles without chitosan at a voltage of 22.5 kV and a flow rate of 0.2 ml/h having a particle size of 231 nm andan encapsulation effciency of 89%, while the paclitaxel loaded zein nanoparticles with chitosan had a particle size of 339nm and an encapsulation effciency of 94%, prepared with 22.5 kV and a flow rate of 0.3 ml/h.

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[1] Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004; 4: 253–265. [CrossRef]
[2] Ramalingam SS, Owonikoko TK, Khuri FR. Lung cancer: New biological insights and recent therapeutic advances. CA Cancer J Clin. 2011; 61(2): 91–112. [CrossRef]
[3] Jemal A, Bray F, Center MM, Ferla J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2): 69– 90. [CrossRef]
[4] Sivarajakumar R, Mallukaraj D, Kadavakollu M, Neelakandan N, Chandran S, Bhojaraj S, Reddy Karri VVS. Nanoparticles for the treatment of lung cancers. J Young Pharm. 2018; 10(3): 276-281. [CrossRef]
[5] Horwitz SB. Taxol (paclitaxel): Mechanisms of action. Ann Oncol: Off J Eur Soc Med Onc. 1994; 5, S3-6.
[6] Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: The drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001; 37: 1590-1598. [CrossRef]
[7] van Tellingen O, Huizing MT, Panday VR, Schellens JH, Nooijen WJ, Beijnen JH. Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients. Br J Cancer. 1999; 81: 330-335. [CrossRef]
[8] Lubejko BG, Sartorius SE. Nursing considerations in paclitaxel (Taxol®) administration. Sem Onc. 1993; 20: 26-30. [CrossRef]
[9] Stinchcombe TE. Nanoparticle albumin-bound paclitaxel: A novel Cremphor-EL-free formulation of paclitaxel. Nanomed. 2007; 2: 415-423. [CrossRef]
[10] Lu J, Huang Y, Zhao W, Marquez RT, Meng X, Li J, Gao X, Venkataramanan R, Wang Z, Li S. PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. Biomat. 2013; 34: 1591-1600. [CrossRef]
[11] Surapaneni MS, Das SK, Das NG. Designing paclitaxel drug delivery systems aimed at improved patient outcomes: current status and challenges. ISRN Pharmacol. 2012: 623139. [CrossRef]
[12] Koudelka S, Turánek J. Liposomal paclitaxel formulations. J Contr Rel. 2012; 163(3): 322-34. [CrossRef]
[13] McCormack B, Gregoriadis G. Entrapment of cyclodextrin-drug complexes into liposomes: potential advantages in drug delivery. J Drug Target. 1994; 2: 449-454. [CrossRef]
[14] Bernsdorff C, Reszka R, Winter R. Interaction of the anticancer agent Taxol™ (paclitaxel) with phospholipid bilayers. J Biomed Mat Res. 1999; 46: 141-149.
[15] Sampedro F, Partika J, Santalo P, Molins-Pujol AM, Bonal J, Perez-Soler R. Liposomes as carriers of different new lipophilic antitumour drugs: A preliminary report. J Microencaps. 1994; 11: 309-318. [CrossRef]
[16] Sharma A, Straubinger RM. Novel taxol formulations: preparation and characterization of taxol-containing liposomes. Pharm Res. 1994; 11: 889-896.
[17] Torchilin V. Multifunctional an
[18] Ruenraroengsak P, Cook JM, Florence AT. Nanosystem drug targeting: Facing up to complex realities. J Contr Rel. 2010; 141: 265-76. [CrossRef]
[19] Sultana S, Khan MR, Kumar M, Kumar S, Ali M. Nanoparticles-mediated drug delivery approaches for cancer targeting: a review. J Drug Target. 2013; 21: 107-25. [CrossRef]
[20] Li L, Ahmed B, Mehta K, Kurzrock R. Liposomal curcumin with and without oxaliplatin: Effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther. 2007; 6(4): 1276-1282. [CrossRef]
[21] Lin CC, Lin HY, Chen HC, Yu MW, Lee MH. Stability and characterisation of phospholipid-based curcuminencapsulated microemulsions. Food Chem. 2009; 116(4): 923-928. [CrossRef]
[22] Yu HL, Huang QR. Enhanced in vitro anti-cancer activity of curcumin encapsulated in hydrophobically modified starch. Food Chem. 2010; 119(2): 669-674. [CrossRef]
[23] Jin C, Bai L, Wu H, Liu J, Guo G, Chen J. Paclitaxel-loaded poly (D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro. Cancer Biol Ther. 2008; 7: 911–916. [CrossRef]
[24] Danhier F, Lecouturier N, Vroman B, Jérôme C, Marchand-Brynaert J, Feron O, Preat V. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation. J Contr Rel. 2009; 133: 11–17. [CrossRef]
[25] Arica-Yegin B, Benoît JP, Lamprecht A. Paclitaxel-loaded lipid nanoparticles prepared by solvent injection or ultrasound emulsification. Drug Dev Ind Pharm. 2006; 32: 1089–1094. [CrossRef]
[26] Jores K, Mehnert W, Drechsler M, Bunjes H, Johann C, Maeder K. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. J Contr Rel. 2004; 95: 217–227. [CrossRef]
[27] Ganta S, Amiji M. Coadministration of Paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm. 2009; 6: 928–939. [CrossRef]
[28] Wang Y, Lu ZX, Lv FX, Bie XM. Study on microencapsulation of curcumin pigments by spray drying. Eur Food Res Tech. 2009; 229(3): 391-396. [CrossRef]
[29] Shaikh J, Ankola DD, Beniwal V, Singh D, Ravi Kumar MNV. Nanoparticle encapsulation improves oral bioavailability ofcurcumin by at least 9-times when compared to curcuminadministered with piperine as absorption enhancer. Eur J Pharm Sci. 2009; 37: 223–30. [CrossRef]
[30] Mukerjee A, Vishwanatha JK. Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Res. 2009; 29(10): 3867-3875.
[31] Prajakta D, Ratnesh J, Chandan K, Suresh S, Grace S, Meera V, Vandana P. Curcumin loaded ph-sensitive nanoparticles for the treatment of colon cancer. J Biomed Nanotech. 2009; 5: 445-455.
[32] Gomez-Estaca J, Balaguer MP, Gavara R, Hernandez-Munoz P. Formation of zein nanoparticles by electrohydrodynamic atomization: Effect of the main processing variables and suitability for encapsulating the food coloring and active ingredient curcumin. Food Hydrocolloids. 2012; 28: 82-91. [CrossRef]
[33] Jaworek A. Electrostatic micro- and nanoencapsulation and electroemulsification: A brief review. J Microencaps. 2008; 25 (7): 443-468. [CrossRef]
[34] Zhang L, Huang J, Si T, Xu RX. Coaxial electrospray of microparticles and nanoparticles for biomedical applications. Expert Rev Med Devices. 2012; 9(6): 595–612. [CrossRef]
[35] Cao L, Luo J, Tu K, Wang LQ, Jiang H. Generation of nano-sized core–shell particles using a coaxialtri-capillary electrospray-template removal method. Coll Surf B: Biointerfaces. 2014; 115: 212–218. [CrossRef]
36] Yun KM, Suryamas AB, Hirakawa C, Iskandar F, Okuyama K. A new physicalroute to produce monodispersed microsphere nanoparticle–polymer composites. Langmuir. 2009; 25: 11038–11042. [CrossRef]
[37] Ding L, Lee T, Wang CH. Fabrication of monodispersed taxol-loaded particles using electrohydrodynamic atomization. J Contr Rel. 2005; 102: 395–413. [CrossRef]
[38] Kim W, Kim SS. Synthesis of biodegradable triple-layered capsules using atriaxial electrospray method. Polymer. 2011; 52: 3325–3336. [CrossRef]
[39] Valo H, Peltonen L, Vehvilainen S, Karjalainen M, Kostiainen R, Laaksonen T, Hirvonen J. Electrospray encapsulation of hydrophilic and hydrophobic drugsin poly (l-lactic acid) nanoparticles. Small. 2009; 5: 1791–1798. [CrossRef]
[40] Zhang S, Kawakami K, Yamamoto M, Masaoka Y, Kataoka M, Yamashita S, Sakuma S. Coaxial electrospray formulations for improving oral absorption of apoorly water-soluble drug. Mol Pharm. 2011; 8: 807–813. [CrossRef]d stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm. 2009; 7: 431- 444. [CrossRef]
41] Chang MW, Stride E, Edirisinghe M. A new method for the preparation of monoporous hollow microspheres. Langmuir. 2010; 26: 5115–5121. [CrossRef]
[42] Zhang S, Kawakami K. One-step preparation of chitosan solid nanoparticlesby electrospray deposition. Int J Pharm. 2010; 397: 211–217. [CrossRef]
[43] Kose MD, Bayraktar O. Encapsulation of lycopene using electrospraying method. Biointerface Res Appl Chem. 2016; 6 (4): 1417-142.
[44] Baspinar Y, Üstündaş M, Bayraktar O, Sezgin C. Response surface methodology for extraction of curcumin from turmeric and piperine from black pepper. Celal Bayar University J Sci. 2017; 13 (3): 747-754. [CrossRef]
[45] Shukla R, Cheryan M. Zein: the industrial protein from corn. Ind Crops Prod. 2001; 13(3): 171-192. [CrossRef]
[46] Patel A, Hu YC, Tiwari JK, Velikov KP. Synthesis and characterisation of zein-curcumin colloidal particles. Soft Matter. 2010; 6(24): 6192-6199. [CrossRef]
[47] Liu XM, Sun QS, Wang HJ, Zhang L, Wang JY. Microspheres of corn protein, zein, for an ivermectin drug delivery system. Biomaterials. 2005; 26(1): 109-115. [CrossRef]
[48] Zhong QX, Jin MF. Nanoscalar structures of spray-dried zein microcapsules and in vitro release kinetics of the encapsulated lysozyme as affected by formulations. J Agricul Food Chem. 2009; 57(9): 3886-3894. [CrossRef]
[49] Nagpal K, Singh SK, Mishra DN. Chitosan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull. 2010; 58: 1423-30. [CrossRef]
[50] Helander IM, Nurmiaho-Lassila EL, Ahvenainen R, Rhoades J, Roller S. Chitosan disrupts the barrier properties of the outer membrane of Gram-negative bacteria. Int J Food Microbiol. 2001; 71(2–3): 235–244. [CrossRef]
[51] Gordon S, Saupe A, McBurney W, Rades T, Hook S. Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery. J Pharm Pharmacol. 2008; 60: 1591-600. [CrossRef]
[52] Luo Y, Wang Q. Recent development of chitosan-based polyelectrolytecomplexes with natural polysaccharides for drug delivery. Int J Biol Macromol. 2014; 64: 353–367. [CrossRef]
[53] Rojanasakul Y, Wang LY, Bhat M, Glover DD, Malanga CJ, Ma JKH. The transport barrier of epithelia: A comparative study on membrane permeability and charge selectivity in the rabbit. Pharm Res. 1992; 9: 1029-1034.
[54] Thanou M, Verhoef JC, Junginger HE. Chitosan and its derivatives as intestinal absorption enhancers. Adv Drug Del Rev. 2001; 50: 91–101. [CrossRef]
[55] Hartman RPA, Brunner DJ, Camelot DMA, Marijnissen JCM, Scarlett B. Electrohydrodynamic atomization in the cone-jet mode physical modeling of the liquid cone and jet. J Aerosol Sci. 1999; 30(7): 823-849. [CrossRef]
[56] Ding L, Lee T, Wang CH. Fabrication of monodispersed taxol-loaded particles using electrohydrodynamic atomization. J Contr Rel. 2005; 102: 395–413. [CrossRef]
[57] Xie JW, Marijnissen JCM, Wang CH. Microparticles developed by electrohydrodynamic atomization for the local delivery of anticancer drug to treat c6 glioma in vitro. Biomat. 2006; 27: 3321–3332. [CrossRef]
[58] Xie J, Ng WJ, Lee LY, Wang C-H. Encapsulation of protein drugs in biodegradable microparticles by co-axial electrospray. J Coll Interf Sci. 2008; 317: 469–476. [CrossRef]
[59] Furman C, Carpentier R, Barczyk A, Chavatte P, Betbeder D, Lipka E. Development and validation of a reversedphase UPLC method for the quantification of paclitaxel in different PLGA nanocarriers. Electrophoresis. 2017; 38: 2536–2541. [CrossRef]
[60] Erel Akbaba G, Akbaba H, Kantarcı AG. Development and in vitro evaluation of positive-charged solid lipid nanoparticles as nucleic acid delivery system in glioblastoma treatment. J Res Pharm. 2018; 22(2): 299-306. [CrossRef]
[61] Baspinar Y, Üstündaş M, Bayraktar O, Sezgin C. Curcumin and piperine loaded zein-chitosan nanoparticles: Development and in-vitro characterisation. Saudi Pharm J. 2018; 26: 323-334. [CrossRef]