title: Temperature/pH Responsive Hydrogels Based on Poly(ethylene glycol) and Functionalized Poly(e-caprolactone) Block Copolymers for Controlled Delivery of Macromolecules.
abstract: OBJECTIVE
  To assess the potential of triblock copolymers based on poly(ethylene glycol) (PEG) and functionalized poly(ε-caprolactone) as temperature/pH responsive gels for controlled delivery of macromolecules.
  
  
  METHODS
  Poly(α-carboxylate-co-α-benzylcarboxylate-ε-caprolactone)-PEG-poly(α-carboxylate-co-α-benzylcarboxylate-ε-caprolactone) (PCBCL-PEG-PCBCL) was synthesized through ring opening polymerization of α-benzyl carboxylate-ε-caprolactone by PEG, followed by 30% debenzylation of the lateral blocks. The effect of Tris buffer and pH on the sol-gel transition temperature of PCBCL-PEG-PCBCL was assessed. The temperature/pH responsive release of tetramethylrhodamine-dextran (TMR-D) (10 and 40 kDa) from PCBCL-PEG-PCBCL was investigated.
  
  
  RESULTS
  Replacement of water with Tris buffer reduced PCBCL-PEG-PCBCL sol-gel transition temperature. Thermo-reversible hydrogels were only formed at pHs ≥ 5.0, but PCBCL-PEG-PCBCL transition temperature was not affected by pH above pH 5.0. In contrast to Pluronic F127 that released 100% of TMR-D within 2 h, PCBCL-PEG-PCBCL hydrogel controlled TMR-D release efficiently at pH = 7.4 and 37°C (~27 and 11% TMRD 10 and 40 kDa release within 150 h, respectively). At 50°C or pH = 9.0, TMR-D release was increased slightly, while at room temperature or pH = 5.0, no control over TMR-D release was observed by PCBCL-PEG-PCBCL hydrogel.
  
  
  CONCLUSIONS
  PCBCL-PEG-PCBCL hydrogel provides depot release of macromolecules at physiological conditions. This release can be triggered through changes in the temperature or pH.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
authors.forename: Nazila Safaei
authors.initials: NS
authors.lastname: Nikouei
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
authors.forename: Nasim
authors.initials: N
authors.lastname: Ghasemi
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. alavasanifar@pharmacy.ualberta.ca.|Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4, Canada. alavasanifar@pharmacy.ualberta.ca.|2-142F Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group/Rexall Centre for Pharmacy & Health Research, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. alavasanifar@pharmacy.ualberta.ca.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry*; D003911:Dextrans / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012235:Rhodamines / Q000008:administration & dosage; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D005456:Fluorescent Dyes; C067661:Fluoro-Ruby; D020100:Hydrogels; D011091:Polyesters; D012235:Rhodamines; C016240:polycaprolactone; D011092:Polyethylene Glycols
keywords: Block copolymers; Drug delivery; TMR-D; Thermos-responsive gels; pH responsive gels