title: Apoptosis induction and anti-cancer activity of LeciPlex formulations.
abstract: OBJECTIVE
  Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery.
  
  
  METHODS
  Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential.
  
  
  RESULTS
  In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system.
  
  
  CONCLUSIONS
  Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.
authors.affiliation: Department Of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz, Mumbai, Maharashtra, 400098, India.
authors.forename: Vivek V
authors.initials: VV
authors.lastname: Dhawan
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Joshi
authors.forename: Ankitkumar S
authors.initials: AS
authors.lastname: Jain
authors.forename: Yuvraj P
authors.initials: YP
authors.lastname: Nikam
authors.forename: Rajiv P
authors.initials: RP
authors.lastname: Gude
authors.forename: Rita
authors.initials: R
authors.lastname: Mulherkar
authors.forename: Mangal S
authors.initials: MS
authors.lastname: Nagarsenker
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D002412:Cations / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D054709:Lecithins / Q000737:chemistry; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D054709:Lecithins