title: Docetaxel-loaded-lipid-based-nanosuspensions (DTX-LNS): preparation, pharmacokinetics, tissue distribution and antitumor activity.
abstract: The purpose of the study was to design lipid-based-nanosuspensions (LNS) for Docetaxel (DTX) without Tween 80 for clinical intravenous administration (i.v.). DTX-LNS were prepared by high pressure homogenization method, and then lyophilization was carried out to improve the stability. The physical-chemical properties in terms of particle size, size distribution, zeta potential and morphology were evaluated, respectively. The in vitro cytotoxic activity was assessed by MTT against SKOV-3 and malignant melanoma B16 cells. The in vivo pharmacokinetics, tissue distribution as well as antitumor efficacy were investigated in B16 melanoma-bearing Kunming mice. The particle size and zeta potential of DTX-LNS were (200.0 ± 3.42)nm and (-11.15 ± 0.99)mV, respectively. Compared with Duopafei, it was shown that DTX-LNS exhibited higher antitumor efficacy by reducing tumor volume (P<0.05) and increasing survival rate in B16 melanoma-bearing mice and strongly reduced the anticancer drug toxicity. The results of biodistribution studies clearly indicated the superiority of DTX-LNS to Duopafei in increasing the accumulation of DTX within tumor and the organs rich in macrophages (liver, lungs and spleen), while, the drug concentration in heart and kidney decreased. Together these results suggested that DTX-LNS could effectively inhibit tumor growth, reduce toxicity during the therapeutic procedure and hold the potential to be an appropriate choice for the clinical administration of DTX.
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan 250012, Shandong Province, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Donghua
authors.initials: D
authors.lastname: Liu
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Zhang
authors.initials: Z
authors.lastname: Juan
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D005562:Formazans / Q000378:metabolism; D006801:Humans; D054709:Lecithins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008545:Melanoma; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms; D010051:Ovarian Neoplasms; D010316:Particle Size; D013535:Suspensions / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005079:Excipients; D005562:Formazans; D054709:Lecithins; D008055:Lipids; D013535:Suspensions; D043823:Taxoids; D013778:Tetrazolium Salts; D000077143:Docetaxel; C079782:MTT formazan