Preparation and Characterization of Novel Drug-Inserted-Montmorillonite Chitosan Carriers for Ocular Drug Delivery
Affiliation(s)
1 College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China. 2 School of Physics and Optoelectronic Engineering, Guangdong University of Technology, Guangzhou, China. 3 College of Pharmacy, China Pharmaceutical University, Nanjing, China.
1 College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China. 2 School of Physics and Optoelectronic Engineering, Guangdong University of Technology, Guangzhou, China. 3 College of Pharmacy, China Pharmaceutical University, Nanjing, China.
ABSTRACT
The objective of the study was to investigate the potential of montmorillonite as a sustained carrier in the preparation of drug-loaded nanoparticles for prolonged ocular application. Nanoparticles were prepared by ionic gelation of chitosan with sodium tripolyphosphate (TPP). Betaxolol hydrochloride (BH) was applied as a model drug. TG, FT-IR, TEM, DLS and XRD have been employed in the characterization of drug-encapsulated chitosan-montmorillonite/TPP nanoparticles (CS-MMT/TPP NPs). TEM images showed that the particles were spherical in shape and had a rough surface. The size range of the nanoparticles was between 338 and 585 nm with positive zeta potential values from 24 mV to 36 mV and encapsulation efficiency values ranging from 12.27% to 50.92%. In vitro sustained drug release was observed with the BH-loaded nanoparticles in artificial tears (pH 7.4). The results of FT-IR, TG and XRD showed that the drug was coated with CSMMT/ TPP NPs. In the mucoadhesion studies, an interaction was found between drug-loaded CSMMT/ TPP NPs and mucin, which could enhance precorneal residence time and hence facilitate an effective sustained release. The optimized formulation was determined to be non-irritant and tolerable by modified Draize test. Therefore, the BH-loading CS-MMT/TPP NPs developed are a promising carrier for controlled drug delivery to the eye.
The objective of the study was to investigate the potential of montmorillonite as a sustained carrier in the preparation of drug-loaded nanoparticles for prolonged ocular application. Nanoparticles were prepared by ionic gelation of chitosan with sodium tripolyphosphate (TPP). Betaxolol hydrochloride (BH) was applied as a model drug. TG, FT-IR, TEM, DLS and XRD have been employed in the characterization of drug-encapsulated chitosan-montmorillonite/TPP nanoparticles (CS-MMT/TPP NPs). TEM images showed that the particles were spherical in shape and had a rough surface. The size range of the nanoparticles was between 338 and 585 nm with positive zeta potential values from 24 mV to 36 mV and encapsulation efficiency values ranging from 12.27% to 50.92%. In vitro sustained drug release was observed with the BH-loaded nanoparticles in artificial tears (pH 7.4). The results of FT-IR, TG and XRD showed that the drug was coated with CSMMT/ TPP NPs. In the mucoadhesion studies, an interaction was found between drug-loaded CSMMT/ TPP NPs and mucin, which could enhance precorneal residence time and hence facilitate an effective sustained release. The optimized formulation was determined to be non-irritant and tolerable by modified Draize test. Therefore, the BH-loading CS-MMT/TPP NPs developed are a promising carrier for controlled drug delivery to the eye.
KEYWORDS
Chitosan, Montmorillonite, Nanoparticles, Mucoadhesive, Sustained Release, Ocular Irritation
Chitosan, Montmorillonite, Nanoparticles, Mucoadhesive, Sustained Release, Ocular Irritation
Cite this paper
Hou, D. , Gui, R. , Hu, S. , Huang, Y. , Feng, Z. and Ping, Q. (2015) Preparation and Characterization of Novel Drug-Inserted-Montmorillonite Chitosan Carriers for Ocular Drug Delivery. Advances in Nanoparticles, 4, 70-84. doi: 10.4236/anp.2015.43009.
Hou, D. , Gui, R. , Hu, S. , Huang, Y. , Feng, Z. and Ping, Q. (2015) Preparation and Characterization of Novel Drug-Inserted-Montmorillonite Chitosan Carriers for Ocular Drug Delivery. Advances in Nanoparticles, 4, 70-84. doi: 10.4236/anp.2015.43009.
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http://link.springer.com/article/10.1023%2FB%3APHAM.0000012145.49054.6c
[1] Quigley, H.A. and Broman, A.T. (2006) The Number of People with Glaucoma Worldwide in 2010 and 2020. British Journal of Ophthalmology, 90, 262-267.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856963/
http://dx.doi.org/10.1136/bjo.2005.081224 [2] Mahalaxmi, D., Samarth, M.M., Shiravadekar, H.S. and Sanghavi, N.M. (1996) Stability-Indicating HPLC Method for Betaxolol HCl and Its Pharmaceutical Dosage Forms. Drug Development and Industrial Pharmacy, 22, 1037-1039.
http://www.tandfonline.com/doi/abs/10.3109/03639049609065938#abstract
http://dx.doi.org/10.3109/03639049609065938 [3] Kaur, I.P. and Kanwar, M. (2002) Ocular Preparations: The Formulation Approach. Drug Development and Industrial Pharmacy, 28, 473-493.
http://www.tandfonline.com/doi/full/10.1081/DDC-120003445#abstract
http://dx.doi.org/10.1081/DDC-120003445 [4] Hamalainen, K.M., Kananen, K., Auriola, S., Kontturi, K. and Urtti, A. (1997) Characterization of Paracellular and Aqueous Penetration Routes in Cornea, Conjunctiva and Sclera. Investigative Ophthalmology and Visual Science, 38, 627-634.
http://www.ncbi.nlm.nih.gov/pubmed/9071216 [5] Keister, J.C., Cooper, E.R., Missel, P.J., Lang, J.C. and Hager, D.F. (1991) Limits on Optimizing Ocular Drug Delivery. Journal of Pharmaceutical Sciences, 80, 50-53.
http://www.ncbi.nlm.nih.gov/pubmed/?term
http://dx.doi.org/10.1002/jps.2600800113 [6] Calvo, C.P., Vila-Jato, J.L. and Alonso, M.J. (1997) Novel Hydrophilic Chitosan-Polyethylene Oxide Nanoparticles as Protein Carriers. Journal of Applied Polymer Science, 63, 125-132.
http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-4628%2819970103%2963:1%3C125::AID-APP13%3E3.0.CO;2-4/abstract
http://dx.doi.org/10.1002/(SICI)1097-4628(19970103)63:1<125::AID-APP13>3.0.CO;2-4 [7] Kaur, I.P. and Smitha, R. (2002) Penetration Enhancers and Ocular Bioadhesives: Two New Avenues for Ophthalmic Drug Delivery. Drug Development and Industrial Pharmacy, 28, 353-369.
http://informahealthcare.com/doi/abs/10.1081/DDC-120002997%20
http://dx.doi.org/10.1081/DDC-120002997 [8] Ludwig, A. (2005) The Use of Mucoadhesive Polymers in Ocular Drug Delivery. Advances Drug Delivery Reviews, 57, 1595-1639.
http://www.ncbi.nlm.nih.gov/pubmed/16198021
http://dx.doi.org/10.1016/j.addr.2005.07.005 [9] Mucha, M. (1997) Rheological Characteristics of Semi-Dilute Chitosan Solutions. Macromolecular Chemistry and Physics, 198, 471-484.
http://onlinelibrary.wiley.com/doi/10.1002/macp.1997.021980220/abstract
http://dx.doi.org/10.1002/macp.1997.021980220 [10] Wang, W. and Xu, D. (1994) Viscosity and Flow Properties of Concentrated Solutions of Chitosan with Different Degrees of Deacetylation. International Journal of Biological Macromolecule, 16, 149-152.
http://www.ncbi.nlm.nih.gov/pubmed/?term
http://dx.doi.org/10.1016/0141-8130(94)90042-6 [11] Alonso, M.J. and Sanchez, A. (2003) The Potential of Chitosan in Ocular Drug Delivery. Journal of Pharmacy and Pharmacology, 55, 1451-1463.
http://onlinelibrary.wiley.com/doi/10.1211/0022357022476/abstract;jsessionid=8714D64E9E7D3894BF48FBA2B0D0912C.f01t04
http://dx.doi.org/10.1211/0022357022476 [12] Bhatta, R.S., Chandasana, H., Chhonker, Y.S., Rathi, C., Kumar, D., Mitra, K. and Shukla, P.K. (2012) Mucoadhesive Nanoparticles for Prolonged Ocular Delivery of Natamycin: In Vitro and Pharmacokinetics Studies. International Journal of Pharmaceutics, 432, 105-112.
http://www.sciencedirect.com/science/article/pii/S0378517312004061
http://dx.doi.org/10.1016/j.ijpharm.2012.04.060 [13] Diebold, A. and Calonge, M. (2010) Applications of Nanoparticles in Ophthalmology. Progress in Retinal and Eye Research, 29, 596-609.
http://www.sciencedirect.com/science?_ob=ArticleListURL&_method=list&_ArticleListID=-782671355&_sort=r&_st=13&view=c&md5=e5bfcd6370882023e9fc1c79a37ae974&searchtype=a
http://dx.doi.org/10.1016/j.preteyeres.2010.08.002 [14] Motwani, S.K., Chopra, S., Talegaonkar, S., Kohli, K., Ahmad, F.J. and Khar, R.K. (2008) Chitosan-Sodium Alginate Nanoparticles as Submicroscopic Reservoirs for Ocular Delivery: Formulation, Optimization and in Vitro Characterization. European Journal of Pharmaceutics and Biopharmaceutics, 68, 513-525.
http://linkinghub.elsevier.com/retrieve/pii/S0939-6411(07)00308-6 [15] Angela, M., Campos, D., Sanchez, A. and Alonso, M.J. (2001) Chitosan Nanoparticles: A New Vehicle for the Improvement of the Delivery of Drugs to the Ocular Surface. Application to Cyclosporin A. International Journal of Pharmaceutics, 224, 159-168.
http://linkinghub.elsevier.com/retrieve/pii/S0378517301007608
http://dx.doi.org/10.1016/S0378-5173(01)00760-8 [16] Ennajih, H., Bouhfid, R., Essassi, E.L.M., Bousmina, M. and El Kadib, A. (2012) Chitosan-Montmorillonite Bio-Based Aerogel Hybrid Microspheres. Microporous and Mesoporous Materials, 152, 208-213.
http://dx.doi.org/10.1002/chem.201104006 [17] Lin, F.H., Lee, Y.H., Jian, C.H., Wong, J.M., Schiech, M.J. and Wang, C.Y. (2002) A Study of Purified Montmorillonite Intercalated with 5-Fluorouracil as Drug Carrier. Biomaterials, 23, 1981-198.
http://www.ncbi.nlm.nih.gov/pubmed/11996039
http://dx.doi.org/10.1016/s0142-9612(01)00325-8 [18] Zheng, J.P., Luan, L., Wang, H.Y., Xi, L.F. and Yao, K.D. (2007) Study on Ibuprofen/Montmorillonite Intercalation Composites as Drug Release System. Applied Clay Science, 36, 297-301.
http://www.sciencedirect.com/science/article/pii/S0169131707000026
http://dx.doi.org/10.1016/j.clay.2007.01.012 [19] Bhatta, R.S., Chandasana, H., Chhonker, Y.S., Rathi, C., Kumar, D., Mitra, K. and Shukla, P.K. (2012) Mucoadhesive Nanoparticles for Prolonged Ocular Delivery of Natamycin: In Vitro and Pharmacokinetics Studies. International Journal of Pharmaceutics, 432, 105-112.
http://www.sciencedirect.com/science/article/pii/S0378517312004061
http://dx.doi.org/10.1016/j.ijpharm.2012.04.060 [20] Qi, L.F., Xu, Z.R., Jiang, X., Hu, C.H. and Zou, X.F. (2004) Preparation and Antibacterial Activity of Chitosan Nanoparticles. Carbohydrate Research, 339, 2693-2700.
http://www.ncbi.nlm.nih.gov/pubmed/15519328
http://dx.doi.org/10.1016/j.carres.2004.09.007 [21] Mahmoud, A.A., El-Feky, G.S., Kamel, R. and Awad, G.E.A. (2011) Chitosan/Sulfobutylether-β-Cyclodextrin Nanoparticles as a Potential Approach for Ocular Drug Delivery. International Journal of Pharmaceutics, 413, 229-236.
http://linkinghub.elsevier.com/retrieve/pii/S0378-5173(11)00358-9
http://dx.doi.org/10.1016/j.ijpharm.2011.04.031 [22] Wilhelmus, K.R. (2001) The Draize Eye Test. Survey of Ophthalmology, 45, 493-515.
http://www.ncbi.nlm.nih.gov/pubmed/11425356
http://dx.doi.org/10.1016/s0039-6257(01)00211-9 [23] Vandenberg, G.W., Drolet, C., Scott, S.L. and Noue, J.D. (2001) Factors Affecting Protein Release from Alginate- Chitosan Coacervate Microcapsules during Production and Gastric/Intestinal Simulation. Journal of Controlled Release, 77, 297-307.
http://www.sciencedirect.com/science/article/pii/S016836590100517X
http://dx.doi.org/10.1016/S0168-3659(01)00517-X [24] Quan, G. and Tao, W. (2007) Chitosan Nanoparticle as Protein Delivery Carrier—Systematic Examination of Fabrication Conditions for Efficient Loading and Release. Colloid and Surfaces B: Biointerfaces, 59, 24-34.
http://www.sciencedirect.com/science/article/pii/S0927776507001671 [25] Kawashima, Y., Yamamoto, H., Takeuchi, H. and Kuno, Y. (2000) Mucoadhesive DL-Lactide/Glycolide Copolymer Nanoparticles Coated with Chitosan to Improve Oral Delivery of Elcatonin. Pharmaceutical Development and Technology, 5, 77-85.
http://informahealthcare.com/doi/abs/10.1081/PDT-100100522%20
http://dx.doi.org/10.1081/PDT-100100522 [26] Oyarzun-Ampuero, F.A., Brea, J., Loza, M.I., Torres, D. and Alonso, M.J. (2009) Chitosan-Hyaluronic Acid Nanoparticles Loaded with Heparin for the Treatment of Asthma. International Journal of Pharmaceutics, 2, 122-129.
http://www.sciencedirect.com/science/article/pii/S0378517309002129
http://dx.doi.org/10.1016/j.ijpharm.2009.04.009 [27] Schiffelers, R.M., Woodle, M.C. and Scaria, P. (2004) Pharmaceutical Prospects for RNA Interference. Pharmacy Research, 21, 1-7.
http://link.springer.com/article/10.1023%2FB%3APHAM.0000012145.49054.6c