Controlling Drug Release from Titania Nanotube Arrays Using Polymer Nanocarriers and Biopolymer Coating

Moom Sinn Aw, Karan Gulati, Dusan Losic

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DOI: 10.4236/jbnb.2011.225058                

Abstract

Titania nanotube arrays (TNT) prepared by self-ordering electrochemical anodization have attracted considerable attraction for the development of new devices for local drug delivery applications. Two approaches to extend drug release of water insoluble drugs by integration TNTs with polymeric micelles and biopolymer coatings are presented in this work. The proposed strategies emphasized on remarkable properties of these materials and their unique combination to design local drug delivery system with advanced performance. The first concept integrates TNTs with drug loaded polymeric micelles (Pluronic F127) as drug nanocarrier, until the second concept includes polymer coating of drug loaded TNT with biodegradable polymer (chitosan). The water insoluble, anti-inflammatory drug, indomethacin was used as a model drug. Both approaches showed a significant improvement of the drug release characteristics, with reduced burst release (from 77% to 39%) and extended overall release from 9 days to more than 28 days. These results suggest the capability of TNT based systems to be applied for local drug delivery deliver over an extended period with predictable kinetics that is particularly important for bone implant therapies.

Keywords

Drug Delivery, Titania Nanotubes, Polymeric Micelles, Pluronic F127, Chitosan, Indomethacin

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. P. Jain, S. Modi, A. J. Domb and N. Kumar, “Roles of Polyanhydrides as Localised Drug Carriers,” Journal of Controlled Release, Vol. 103, 2005, pp. 541-563. doi:10.1016/j.jconrel.2004.12.021
[2]	M. M. de Villiers, P. Aramwit and G. S. Kwon, “Nanotechnology in Drug Delivery,” American Association of Pharmaceutical Science (AAPS) Press, Springer Science, 2009.
[3]	J. Venugopal, M. P. Prabhakaran, S. Low, A. T. Choon, Y. Z. Zhang, G. Deepika and S. Ramakrishna, “Nano-technology for Nanomedicine and Delivery of Drugs,” Current Pharmaceutical Design, Vol. 14, No. 22, 2008, pp. 2184-2200. doi:10.2174/138161208785740180
[4]	N. A. Ochekpe, P. O. Olorunfemi and N. C. Ngwuluka, “Nanotechnology and Drug Delivery Part 2: Nanostructures for Drug Delivery,” Tropical Journal of Pharmaceutical Research, Vol. 8, No. 3, 2009, pp. 275-28. doi:10.4314/tjpr.v8i3.44547
[5]	M. Vallet-Regí, F. Balas and D. Arcos, “Mesoporous Materials for Drug Delivery,” Angewandte Chemie International Edition, Vol. 46, No. 40, 2007, pp. 7548-7558. doi:10.1002/anie.200604488
[6]	D. Losic and S. Simovic, “Self-Ordered Nanopore and Nanotube Platforms for Drug Delivery Applications,” Expert Opinion in Drug Delivery, Vol. 6, No. 12, 2009, pp. 1363-1380. doi:10.1517/17425240903300857
[7]	A. Ghicov and P. Schmuki, “Self-Ordering Electrochemistry: A Review on Growth and Functionality of TiO2 Nanotubes and Other Self-Aligned MOx Structures,” Chemical Communications, Vol. 20, 2009, pp. 2791- 2808. doi:10.1039/b822726h
[8]	D. Losic, L. Velleman, K. Kant, T. Kumeria, K. Gulati, J. G. Shapter, D. A. Beattie and S. Simovic, “Self-Ordering Electrochemistry: A Simple Approach for Engineering Nanopore and Nanotube Arrays for Emerging Applications,” Australian Journal of Chemistry, Vol. 64, No. 3, 2010, pp. 294-301. doi:10.1071/CH10398
[9]	C. A. Grimes, “Synthesis and Application of Highly Ordered Arrays of TiO2 Nanotubes,” Journal of Material Chemistry, Vol. 17, 2007, pp. 1451-1457. doi:10.1039/b701168g
[10]	K. C. Popat, L. Leoni, C. A. Grimes and T. A. Desai, “Influence of Engineered Titania Nanotubular Surfaces on Bone Cells,” Biomaterials, Vol. 28, No. 21, 2007, pp. 3188-3197. doi:10.1016/j.biomaterials.2007.03.020
[11]	P. A. Tran, L. Sarin, R. H. Hurt and T. J. Webster, “Opportunities for Nanotechnology-Enabled Bioactive Bone Implants,” Journal of Material Chemistry, Vol. 19, No. 18, 2009, pp. 2653-2659. doi:10.1039/b814334j
[12]	E. Alpaslan, B. Ercan and T. J. Webster, “Anodized 20 nm Diameter Nanotubular Titanium for Improved Bladder Stent Applications,” International Journal of Nano-medicine, Vol. 6, 2011, pp. 219-225.
[13]	J. Park, S. Bauer, K. von der Mark and P. Schmuki, “Nanosize and Vitality: TiO2 Nanotube Diameter Directs Cell Fate,” Nano Letters, Vol. 7, No. 6, 2007, pp. 1686- 1691. doi:10.1021/nl070678d
[14]	Y. Y. Song, F. Schmidt-Stein, S. Bauer and P. Schmuki, “Amphiphilic TiO2 Nanotube Arrays: An Actively Controllable Drug Delivery System,” Journal of American Chemical Society, Vol. 131, No. 12, 2009, pp. 4230-4233. doi:10.1021/ja810130h
[15]	L.M. Chamberlain, K. S. Brammer, G. W. Johnston, S. Chien and S. Jin, “Microphage Inflammatory Response to TiO2 Nanotube Surface,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, 2011, pp. 293-300. doi:10.4236/jbnb.2011.23036
[16]	H. Liu and T. J. Webster, “Nanomedicine for Implants: A Review of Studies and Necessary Experimental Tools,” Biomaterials, Vol. 28, No. 2, 2007, pp. 354-369. doi:10.1016/j.biomaterials.2006.08.049
[17]	D. Losic, M. A. Cole, B. Dollmann, K. Vasilev and H. J. Griesser, “Surface Modification of Nanoporous Alumina Membranes by Plasma Polymerization,” Nanotechnology, Vol. 19, No. 24, 2008, pp. 5704-5711. doi:10.1088/0957-4484/19/24/245704
[18]	S. Simovic, D. Losic and K. Vasilev, “Controlled Drug Release from Porous Materials by Plasma Polymer Deposition,” Chemical Communications, Vol. 46, No. 8, 2009, pp. 1317-1319. doi:10.1039/b919840g
[19]	K. Vasilev, Z. Poh, K. Kant, J. Chan, A. Michelmore and D. Losic, “Tailoring the Surface Functionalities of Titania Nanotube Arrays,” Biomaterials, Vol. 31, No. 3, 2010, pp. 532-540. doi:10.1016/j.biomaterials.2009.09.074
[20]	M. S. Aw, S. Simovic, J. Addai-Mensah and D. Losic, “Polymeric Micelles in Porous and Nanotubular Implants as a New System for Extended Delivery of Poorly Soluble Drugs,” Journal of Material Chemistry, Vol. 21, No. 20, 2011, pp. 7082-7089. doi:10.1039/c0jm04307a
[21]	L. Qiu, C. Zheng, Y. Jin and K. Zhu, “Polymeric Micelles as Nanocarriers for Drug Delivery,” Expert opinions on therapeutic patents, Vol. 17, No. 7, 2007, pp. 819-830.
[22]	M. L. Adams, A. Lavasanifar and G. S. Kwon, “Amphiphilic Block Copolymers for Drug Delivery,” Journal of Pharmaceutical Sciences, Vol. 92, No. 7, 2003, pp. 1343-1355. doi:10.1002/jps.10397
[23]	A. V. Kabanov, E. V. Batrakova and V. Y. Alakhov, “Pluronic? Block Copolymers as Novel Polymer Therapeutics for Drug and Gene Delivery,” Journal of Controlled Release, Vol. 82, No. 2-3, 2002, pp. 189-212. doi:10.1016/S0168-3659(02)00009-3
[24]	A. K. Singla and M. Chawla, “Chitosan: Some Pharmaceutical and Biological Aspects—An Update,” Journal of Pharmacy and Pharmacology, Vol. 53, No. 8, 2001, pp. 1047-1067. doi:10.1211/0022357011776441
[25]	H. Ueno, H. Yamada, I. Tanaka, N. Kaba, M. Matsuura and M. Okumura, “Accelerating Effects of Chitosan for Healing at Early Phase of Experimental Open Wound in Dogs,” Biomaterials, Vol. 20, No. 15, 1999, pp. 1407-1414. doi:10.1016/S0142-9612(99)00046-0
[26]	Y. Hu, J. Wang, Z. Zhi, T. Jiang and S. Wang, “Facile Synthesis of 3D Cubic Mesoporous Silica Microspheres with a Controllable Pore Size and Their Application for Improved Delivery of a Water-Insoluble Drug,” Journal of Colloid and Interface Science, Vol. 363, No. 1, 2011, pp. 410-417. doi:10.1016/j.jcis.2011.07.022
[27]	K. Kant and D. Losic, “A Simple Approach for Synthesis of TiO2 Nanotubes with Through-Hole Morphology,” Physica Status Solidi (RRL)—Rapid Research Letters, Vol. 3, No. 5, 2009, pp. 139-141.
[28]	K. Kant and D. Losic, “Self-Ordering Electrochemical Synthesis of TiO2 Nanotube Arrays: Controlling the Nanotube Geometry and the Growth Rate,” International Journal of Nanoscience, Vol. 10, No. 1-2, 2011, pp. 1-6. doi:10.1142/S0219581X11007466
[29]	Z. L. Tyrrell, Y. Shen and M. Radosz, “Fabrication of Micellar Nanoparticles for Drug Delivery through the Self-Assembly of Block Copolymers,” Progress in Polymer Science, Vol. 35, No. 9, 2010, pp. 1128-1143. doi:10.1016/j.progpolymsci.2010.06.003
[30]	G. Bonacucina, M. Cespi, G. Mencarelli, G. Giorgioni and G. F. Palmieri, “Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems,” Polymers, Vol. 3, No. 2, 2011, pp. 779-811. doi:10.3390/polym3020779
[31]	A. Y. Polishcuck, L. A. Zimina, R. Y. Ksenko, A. L. Iordanskii and G. E. Zaikov, “Diffusion-Activation Laws for Drug Release from Polymer Matrices,” Polymer Degradation and Stability, Vol. 31, No. 2, 1991, pp. 247- 254. doi:10.1016/0141-3910(91)90079-7
[32]	S. A. Agnihotri, N. N. Mallikarjuna and T. M. Aminabhavi, “Recent Advances on Chitosan-Based Micro- and Nanoparticles in Drug Delivery,” Journal of Controlled Release, Vol. 100, No. 1, 2004, pp. 5-28. doi:10.1016/j.jconrel.2004.08.010
[33]	J. D. Bumgardner, R. Wiser, P. D. Gerard, P. Bergin, B. Chestnutt, M. Marini, V. Ramsey, S. H. Elder and J. A. Gilbert, “Chitosan: Potential Use as a Bioactive Coating for Orthopaedic and Craniofacial/Dental Implants,” Journal of Biomaterials Science-Polymer Edition, Vol. 14, No. 5, 2003, pp. 423-438. doi:10.1163/156856203766652048