Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines

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• 作者：Sharan Bobbala ; Viral Tamboli ; Arlene McDowell ; Ashim K. Mitra…
• 关键词：nanoparticles ; pentablock copolymers ; sustained release ; thermoresponsive hydrogels ; vaccine delivery
• 刊名：The AAPS Journal
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：18
• 期：1
• 页码：261-269
• 全文大小：248 KB
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• 作者单位：Sharan Bobbala (1)
  Viral Tamboli (2)
  Arlene McDowell (1)
  Ashim K. Mitra (2)
  Sarah Hook (1)
  
  1. School of Pharmacy, University of Otago, Dunedin, 9054, New Zealand
  2. School of Pharmacy, UMKC, Kansas City, Missouri, USA
  
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Biotechnology; Pharmacy;
• 出版者：Springer US
• ISSN：1550-7416

文摘

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. KEY WORDS nanoparticles pentablock copolymers sustained release thermoresponsive hydrogels vaccine delivery