title: Plasma stable, pH-sensitive non-ionic surfactant vesicles simultaneously enhance antiproliferative effect and selectivity of Sirolimus.
abstract: OBJECTIVE
  The purpose of the present investigation was to prepare a plasma stable, pH-sensitive niosomal formulation to enhance Sirolimus efficacy and selectivity.
  
  
  METHODS
  pH-sensitive niosomal formulations bearing PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymers and cholesteryl hemisuccinate (CHEMS) were prepared by a modified ethanol injection method and characterized with regard to pH-responsiveness and stability in human serum. The ability of pH-sensitive niosomes to enhance the Sirolimus cytotoxicity was evaluated in vitro using human erythromyeloblastoid leukemia cell line (K562) and compared with cytotoxicity effect on human umbilical vein endothelial cells (HUVEC).
  
  
  CONCLUSIONS
  This study showed that both formulations can be rendered pH-sensitive property and were found to rapidly release their contents under mildly acidic conditions. However, the CHEMS-based niosomes lost their pH-sensitivity after incubation in plasma, whereas, PEG-PMMI-CholC6 niosomes preserved their ability to respond to pH change. Sirolimus encapsulated in pH-sensitive niosomes exhibited a higher cytotoxicity than the control conventional formulation on K562 cell line. On the other hand, both pH-sensitive niosomes showed lower antiproliferative effect on HUVEC cells.
  
  
  CONCLUSIONS
  Plasma stable, pH-sensitive PEG-PMMI-CholC6-based niosomes can improve the in vitro efficiency and also reduce the side effects of Sirolimus.
authors.affiliation: Faculty of Pharmacy, Research Center for Pharmaceutical Nanotechnology .
authors.forename: Saeed
authors.initials: S
authors.lastname: Ghanbarzadeh
authors.forename: Arash
authors.initials: A
authors.lastname: Khorrami
authors.forename: Zhaleh
authors.initials: Z
authors.lastname: Pourmoazzen
authors.forename: Sanam
authors.initials: S
authors.lastname: Arami
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002788:Cholesterol Esters / Q000737:chemistry; D004355:Drug Stability; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020014:K562 Cells; D008081:Liposomes; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D020123:Sirolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013386:Succinates / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D002788:Cholesterol Esters; D008081:Liposomes; D011108:Polymers; D013386:Succinates; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C005229:itaconic acid; C013440:cholesteryl succinate; D020123:Sirolimus
keywords: Antiproliferative effect; Sirolimus; pH-sensitive plasma stable niosome