Development and characterization of paclitaxel and embelin loaded solid lipid nanoparticles for breast cancer
In an effort to develop an alternative formulation of combination of paclitaxel (PTX) and embelin (EMB) suitable for parenteral administration, PTX-EMB loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared, characterized and examined for in vitro cytotoxicity. The SLNs, comprising glycerol mono stearate (GMS) as a solid lipid core, Brij 35 used as surfactant and PEGylated phospholipid used as stabilizer, were prepared using a hot homogenization method. Optimized PTX-EMB loaded formulation, the particle sizes of the prepared SLNs were around 300 nm, suggesting that they would be suitable as a parenteral formulation. Transmission electron microscopy showed that the SLNs were homogeneous and spherical in shape. Entrapment efficiency of paclitaxel and embelin was 92.83 ± 2.2%, 83.25 ± 2.4% respectively. An in vitro drug release study were performed in PBS (pH 7.4) for 80 hrs and observed that paclitaxel and embelin released from the PEGylated SLNs was 93.91 ± 4.1 % and 75.63 ± 4.37 % respectively. Furthermore, treatment of the MCF-7 breast cancer cell line with PTX-EMB loaded SLNs yielded cytotoxicities comparable to PTX solution, PTX-EMB mixture solution and PTX loaded PEGylated SLNs. These results collectively suggest that our optimized SLN formulation may have a potential as alternative delivery system for parenteral administration of paclitaxel and embelin.
Keywords: Embelin, Apoptosis, Cancer, Cytotoxicity, Breast Cancer, Solid lipid nanoparticles.
2. Ahn KS, Sethi G, Aggarwal BB. (2007). Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein, blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Mol Pharmacol, 71, 209-219.
3. Nikolovska-Coleska Z, Xu L, Hu Z, Tomita Y, Li P, Roller PP, Wang R, Fang X, Guo R & Zhang M. (2004). Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. Journal of medicinal chemistry 47: 2430-2440.
4. Chaibva F & Walker R. (2007). Development and validation of a stability-indicating analytical method for the quantitation of oxytocin in pharmaceutical dosage forms. Journal of pharmaceutical and biomedical analysis 43: 179-185.
5. Reddy LH & Murthy R. (2005). Etoposide-loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release, and stability evaluation. AAPS PharmSciTech 6: E158-E166
6. Lee MK, Lim SJ & Kim CK. (2007). Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles. Biomaterials 28: 2137-2146.
7. Horwitz K, Costlow M & Mcguire W. (1975). MCF-7: a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. Steroids 26: 785-795.
8. Keizer H, Pinedo H, Schuurhuis G & Joenje H. (1990). Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacology & therapeutics 47: 219-231.
9. Gabizon A, Shmeeda H & Barenholz Y. (2003). Pharmacokinetics of pegylated liposomal doxorubicin. Clinical pharmacokinetics 42: 419-436.
10. Chaudhari KR, Ukawala M, Manjappa AS, Kumar A, Mundada PK, Mishra AK, Mathur R, Mönkkönen J & Murthy RSR. (2012). Opsonization, biodistribution, cellular uptake and apoptosis study of PEGylated PBCA nanoparticle as potential drug delivery carrier. Pharmaceutical research, 29, 53-68.
11. Ferrari M, Fornasiero MC & Isetta AM. (1990). MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. Journal of immunological methods 131: 165-172.
12. Moaddab S, Ahari H, Shahbazzadeh D, Motallebi AA, Anvar AA, Rahman-Nya J & Shokrgozar MR. (2011). Toxicity study of nanosilver (Nanocid) on osteoblast cancer cell line. Int Nano Lett 1: 11-16.
13. Müller R, Schmidt S, Buttle I, Akkar A, Schmitt J & Brömer S. (2004). SolEmuls®-novel technology for the formulation of i.v. emulsions with poorly soluble drugs. International journal of pharmaceutics 269: 293-302.
14. Acharya S, Dilnawaz F & Sahoo SK. (2009). Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy. Biomaterials 30: 5737-5750
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