Polymeric Micelles for Enhanced Solubility of Meloxicam in Oral Drug Delivery

Abstract:

N-arylsuccinyl chitosan was successfully synthesized by introducing hydrophobic and hydrophilic moieties into the chitosan backbone. Incorporation efficiency of the drug-loaded micelles, particle size, in vitro cytotoxicity, and in vitro drug release were investigated. Meloxicam (MX) as a model drug was loaded into the inner core of the micelles by solvent evaporation method. The critical micelle concentration (CMC) of micelles was found to be 0.0385 mg/ml. N-arylsuccinyl chitosan micelles were able to entrap hydrophobic drug (MX) and have particle sizes in the range of 342.1- 444.2 nm. The micelles could enhance solubility of MX with high incorporation efficiency (32.72%). The cytotoxicity in Caco-2 cells to be dependent on the concentration of N-arylsuccinyl chitosan with the IC₅₀ value of 3.23 +/- 0.08 mg/ml. Therefore, N-arylsuccinyl chitosan polymeric micelle presents interest to improve solubility of hydrophobic drug for oral drug delivery.

• Periodical: Advanced Materials Research (Volume 1060)
• Pages: 7-11
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.1060.7
• Online since: December 2014
• Authors: Thisirak Woraphatphadung, Warayuth Sajomsang, Theerasak Rojanarata, Tanasait Ngawhirunpat, Praneet Opanasopit*
• Keywords: N-Arylsuccinyl Chitosan, Polymeric Micelles, Poorly Water-Soluble Drug

References

[1] H.M. Aliabadi, S. Elhasi, A. Mahmud, R. Gulamhusein, P. Mahdipoor, A. Lavasanifar, Encapsulation of hydrophobic drugs in polymeric micelles through co-solvent evaporation: The effect of solvent composition on micellar properties and drug loading, Int. J. Pharm. 329 (2007).

DOI: 10.1016/j.ijpharm.2006.08.018

[2] Y. Lu, K. Park, Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs, Int J Pharm. 453(1) (2013) 198-214.

DOI: 10.1016/j.ijpharm.2012.08.042

[3] S. G¨okt¨urk, E. C¸alıs¸kan, R. Y. Talman, U. Var, A study on solubilization of poorly soluble drugs by cyclodextrins and micelles: complexation and binding characteristics of sulfamethoxazole and trimethoprim Sci World J. (2012) 1-12.

DOI: 10.1100/2012/718791

[4] M. Yokoyama, Clinical application of polymeric micelle carrier systems in chemotherapy and image diagnosis of solid tumor, J Exp Clin Med. 3(4) (2011) 151-158.

[5] Y. Wu, M. Li and H. Gao, Polymeric micelle composed of PLA and chitosan as a drug carrier, Journal Polym Res. 16(1) (2009) 11–18.

DOI: 10.1007/s10965-008-9197-z

[6] W. Sajomsang, S. Tantayanon, V. Tangpasuthadol, M. Thatte, W.H. Daly, Synthesis and characterization of N-aryl chitosan derivatives, Int J Biol Macromol. 43 (2008) 79-87.

DOI: 10.1016/j.ijbiomac.2008.03.010

[7] S. Daungjit, P. Opanasopit, T. Rojanarata, T. Ngawhirunpat, Evaluation of meloxicam-loaded cationic transfersomes as transdermal drug delivery carriers, American Association of Pharmaceutical Sciences Technology. 14(1) (2013) 133-140.

DOI: 10.1208/s12249-012-9904-2

[8] T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Methods. 65 (1983) 55-63.

DOI: 10.1016/0022-1759(83)90303-4

[9] P. Opanasopit, T. Ngawhirunpat, T. Rojanarata, C. Choochottiro, S. Chirachanchai, Camptothecin-incorporating N-phthaloylchitosan-g-mPEG self-assembly micellar system: Effect of degree of deacetylation, Colloids Surf., B. 60 (2007) 117-124.

DOI: 10.1016/j.colsurfb.2007.06.001

[10] T. Ngawhirunpat, N. Wonglertnirant, P. Opanasopit, U. Ruktanonchai, R. Yoksan, K. Wasanasuk et al, Incorporation methods for cholic acid chitosan-g-mPEG self-assembly micellar system containing camptothecin, Colloids Surf., B. 74 (2009) 253-259.

DOI: 10.1016/j.colsurfb.2009.07.027

[11] L. Gao, D. Zhang, M. Chen, Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system, J. Nanopart. Res. 10(5) 2008 845-862.

DOI: 10.1007/s11051-008-9357-4