title: Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.
abstract: The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, 9054, New Zealand.
authors.forename: Sharan
authors.initials: S
authors.lastname: Bobbala
authors.affiliation: School of Pharmacy, UMKC, Kansas City, Missouri, USA.
authors.forename: Viral
authors.initials: V
authors.lastname: Tamboli
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, 9054, New Zealand.
authors.forename: Arlene
authors.initials: A
authors.lastname: McDowell
authors.affiliation: School of Pharmacy, UMKC, Kansas City, Missouri, USA.
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, 9054, New Zealand. sarah.hook@otago.ac.nz.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D020100:Hydrogels / Q000737:chemistry*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols; D011108:Polymers; D013696:Temperature; D014612:Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014783:Viscosity
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D019496:Cancer Vaccines; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011091:Polyesters; D011108:Polymers; D014612:Vaccines; C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); C499774:polyethylene glycol-polylactide-polyethylene glycol; C016240:polycaprolactone; D011092:Polyethylene Glycols
keywords: nanoparticles; pentablock copolymers; sustained release; thermoresponsive hydrogels; vaccine delivery