title: Synthesis and evaluation of biodegradable PCL/PEG nanoparticles for neuroendocrine tumor targeted delivery of somatostatin analog.
abstract: OBJECTIVE
  Neuroendocrine tumors often present a diagnostic and therapeutic challenge. We have aimed to synthesize and develop biodegradable nanoparticles of somatostatin analogue, octreotide for targeted therapy of human neuroendocrine pancreatic tumor.
  
  
  METHODS
  Direct solid phase peptide synthesis of octreotide was done. Octreotide loaded PCL/PEG nanoparticles were prepared by solvent evaporation method and characterized for transmission electron microscopy, differential scanning calorimetery (DSC), Zeta potential measurement studies. The nanoparticles were evaluated in vitro for release studies and peptide content. For biological evaluations, receptor binding & cytotoxicity studies were done on BON-1 neuroendocrine tumor cell line. Biodistribution of radiolabeled peptide and nanoparticles, tumor regression studies were performed on tumor-bearing mouse models.
  
  
  RESULTS
  We have synthesized and purified octreotide with the purity of 99.96% in our laboratory. PEG/PCL nanoparticles with an average diameter of 130-195 nm having peptide loading efficiency of 66-84% with a negative surface charge were obtained with the formulation procedure. Octreotide nanoparticles have a negative action on the proliferation of BON-1 cells. In vivo biodistribution studies exhibited major accumulation of octreotide nanoparticles in tumor as compared to plain octreotide. Octreotide nanoparticles inhibited tumor growth more efficiently than free octreotide.
  
  
  CONCLUSIONS
  Thus, it was concluded that the PCL/PEG nanoformulation of octreotide showed high tumor uptake due to the enhanced permeation and retention (EPR) effect and then peptide ligand imparts targetability to the sst2 receptor and there by showing increase tumor growth inhibition. Selective entry of nanoparticles to the tumor also give the reduce side effects both in vivo and in vitro.
authors.affiliation: School of Pharmaceutical Sciences, Drug Discovery Lab, Rajiv Gandhi Technological University, Bhopal, India.
authors.forename: Nazneen
authors.initials: N
authors.lastname: Dubey
authors.forename: Raunak
authors.initials: R
authors.lastname: Varshney
authors.forename: Jaya
authors.initials: J
authors.lastname: Shukla
authors.forename: Aditya
authors.initials: A
authors.lastname: Ganeshpurkar
authors.forename: Puja P
authors.initials: PP
authors.lastname: Hazari
authors.forename: Guru P
authors.initials: GP
authors.lastname: Bandopadhaya
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005027:Ethylene Oxide / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D015282:Octreotide / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques / Q000379:methods; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D007783:Lactones; C400421:PLC(20)-b-PEO(44); D013004:Somatostatin; D005027:Ethylene Oxide; D015282:Octreotide