title: A novel submicron emulsion system loaded with vincristine-oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies.
abstract: BACKGROUND
  Vincristine (VCR), which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect.
  
  
  METHODS
  After the formation of a VCR-oleic acid ion-pair complex (VCR-OA), the VCR-OA-loaded submicron emulsion (VCR-OA-SME), prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated.
  
  
  RESULTS
  The submicron-emulsion formulation exhibited a homogeneous round shape. The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ± 12.6 nm, -26.5 ± 5.0 mV and 78.64% ± 3.44%, respectively. An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase) and the rest of the drug was detected in the subsequent sustained-release phase. Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0-∞] increased from 187.19 to 227.56 minutes), higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL), and greater area under the curve (area under the curve [0-∞] from 11,417.77 μg/L/minute to 17,164.34 μg/L/minute. Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P < 0.05) on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P < 0.05).
  
  
  CONCLUSIONS
  The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Sichuan University, Chengdu, People's Republic of China.
authors: Ting
authors: T
authors: Zhang
authors: Yong
authors: Y
authors: Zheng
authors: Qiang
authors: Q
authors: Peng
authors: Xi
authors: X
authors: Cao
authors: Tao
authors: T
authors: Gong
authors: Zhirong
authors: Z
authors: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004655:Emulsions / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D019301:Oleic Acid / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014750:Vincristine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004655:Emulsions; D019301:Oleic Acid; D014750:Vincristine
keywords: apoptosis; cell uptake; cytotoxicity; ion-pair complex; submicron emulsion
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