Enhancement of oral bioavailability via solid lipid nanoparticles of anticancer drug dasatinib - An in vitro cytotoxicity and pharmacokinetic study
Objective: Dasatinib (DST) is a BCS Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of DST leads to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of DST. Animal data suggests that the absolute bioavailability of DST is about 14 to 34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid–based drug delivery systems like solid lipid nanoparticles can be used.
Methods: Solid lipid nanoparticles (SLNs) are sub-micron colloidal carriers having a size range of 50–1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. Dasatinib can be conveniently loaded into solid lipid nanoparticles to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of dasatinib suspension.
Results: In vitro cytotoxicity study were done by MTT assay method through ATCC cell lines, the percent inhibition was more in SLN when compared with Suspension. The Pharmacokinetics of dasatinib-SLNs after oral administration in male wistar rats was studied. The bioavailability of dasatinib was increased by 2.28 fold when compared with that of a dasatinib suspension.
Conclusion: The results are indicative of SLNs as suitable lipid based carrier system for improving the oral bioavailability of dasatinib.
2. Mehnert W, Mader K. Solid lipid nanoparticles production, characterization and applications. Adv Drug Deliv Rev 2012;64:83–101.
3. Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm 2000;50:161–77.
4. Muhlen AZ, Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled release drug delivery – drug release and release mechanism. Eur J Pharm Biopharm 1998; 45:149–55.
5. C. Olbrich, O. Kayser, R.H. Müller, Lipase degradation of dynasan 114 and 116 solid lipid nanoparticles (SLN)-effect of surfactants, storage time and crystalinity, Int. J. Pharm. 237 (2002) 119–128.
6. S. Yang, J. Zhu, Y. Lu, B. Liang, C. Yang, Body distribution of camptothecin solid lipid nanoparticles after oral administration, Pharm. Res. 16 (1999) 751–757.
7. Dahan A, Hoffman A. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs. J Control Release 2008;129:1–10.
8. Zheng W, Jain A, Papoutsakis D, et al. Selection of oral bioavailability enhancing formulations during drug discovery. Drug Dev Ind Pharm 2012;38:235–47.
9. Kuldeep R, Sunil KJ, Colorectal cancer-targeted delivery of oxaliplatin via folic acid-grafted solid lipid nanoparticles: preparation, optimization, and in vitro evaluation. Artificial cells, nanomed and biotech. Early online August, 2017; doi.org/10.1080/21691401.2017.1366338.
10. Zhang Q, Yang G, Liu H, et al. Preparation of a novel glycidyl methacrylate-based monolith and its application for the determination of m-nisoldipine in human plasma. J Chromatogr Sci 2010;48: 517–22.
11. Li M, Wang Q, Wang C, et al. Tissues distribution of R-(_)- and S-(+)-m-nisoldipine after single enantiomer administration in rats. Drug Dev Ind Pharm 2009;35:65–72.
12. N. Vijaykumar, P. Raviraj, V. Venkateshwarlu, T. Harisudhan, Development and characterization of solid oral dosage form incorporating candesartan nanoparticles, Pharm. Dev. Tech. 14 (2009) 290–298.
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