title: Formulation of plumbagin loaded long circulating pegylated liposomes: in vivo evaluation in C57BL/6J mice bearing B16F1 melanoma.
abstract: OBJECTIVE
  Plumbagin (2-methyl, 5-hydroxy, 1, 4-naphthoquinone), an anticancer agent is encapsulated either as conventional or long circulating liposomal formulations to enhance its biological half-life and antitumor efficacy.
  
  
  METHODS
  The liposomes were prepared by thin film hydration method and in vitro characterization was carried out to examine the particle size, zeta potential, drug encapsulation efficiency and in vitro release. The optimized formulations were tested for pharmacokinetic and pharmacodynamic efficacy against mice bearing B16F1 melanoma. Also in vivo toxicity studies were carried out.
  
  
  CONCLUSIONS
  The optimum particle size and entrapment efficiency was observed at drug to lipid molar ratio of 1:20. The in-vitro release of plumbagin from the liposomal formulations in phosphate-buffered saline (pH 7.4) showed biphasic release with an initial burst release followed by sustained release phase. Elimination half life (T(½)) of pegylated, conventional and free plumbagin was 1305.76 ± 278.16, 346.87 ± 33.82 and 35.89 ± 7.95 min respectively. Further, plumbagin exhibited better antitumor efficacy in vivo when administered as long circulating liposomes with no signs of normal tissue toxicity.
  
  
  CONCLUSIONS
  It can be concluded that the pegylated liposomes could provide a promising parenteral platform for plumbagin with enhanced plasma half-life and therapeutic efficacy.
authors.affiliation: Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, MU, Manipal, India.
authors.forename: M R Sunil
authors.initials: MR
authors.lastname: Kumar
authors.forename: B Kiran
authors.initials: BK
authors.lastname: Aithal
authors.forename: N
authors.initials: N
authors.lastname: Udupa
authors.forename: M Sreenivasulu
authors.initials: MS
authors.lastname: Reddy
authors.forename: V
authors.initials: V
authors.lastname: Raakesh
authors.forename: R S R
authors.initials: RS
authors.lastname: Murthy
authors.forename: D Prudhvi
authors.initials: DP
authors.lastname: Raju
authors.forename: B S Satish
authors.initials: BS
authors.lastname: Rao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D018675:Toxicity Tests
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D008081:Liposomes; D009285:Naphthoquinones; D011092:Polyethylene Glycols; C014758:plumbagin