title: In vitro cytotoxicity and bioavailability of solid lipid nanoparticles containing tamoxifen citrate.
abstract: The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate (TC) on the in vitro antitumor activity and bioavailability of the drug. TC-loaded SLN were prepared by solvent injection method using glycerol monostearate (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by poloxamer 188 showed highest entrapment efficiency % (86.07 ± 1.74 and 90.40 ± 1.22%) and reasonable mean particle sizes (130.40 ± 9.45 and 243.80 ± 12.33 nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial burst effect followed by a sustained drug release. In vitro cytotoxicity of F3 against human breast cancer cell line MCF-7 showed comparable antitumor activity to free drug. Moreover, the results of bioavailability evaluation of TC-loaded SLN in rats compared to free TC indicated that 160.61% increase in the oral bioavailability of TC. The obtained results suggest that incorporation of the poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and significantly enhance oral bioavailability of TC in rats.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University , Cairo , Egypt and.
authors.forename: Fahima M
authors.initials: FM
authors.lastname: Hashem
authors.forename: Mohamed
authors.initials: M
authors.lastname: Nasr
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khairy
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D008055:Lipids; D013629:Tamoxifen