A novel vaccine delivery system: Biodegradable nanoparticles in thermosensitive hydrogel

Abstract

In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature. The in vitro release profile showed that bFGF could be released from bFGF-NPs or bFGF-NPs/hydrogel at an extended period, but the release rate of bFGF-NPs/hydrogel was much lower. In vivo experiments suggested that immunogenicity of bFGF improved significantly after being incorporated into the NPs/hydrogel composite, and strong humoral immunity was maintained for longer than 12 weeks. Furthermore, an in vivo protective anti-tumor immunity assay indicated that immunization with bFGF-NPs/hydrogel could induce significant suppression of the growth and metastases of tumors. Thus, the NPs/hydrogel composite may have great potential application as a novel vaccine delivery system.

Subunit Vaccine Delivery

“…In the case of PCEC and PECE, PCEC nanoparticles loaded with human bFGF were incorporated into a PECE-based thermosensitive gel. Entirely consistent with the general properties of gel delivery systems, a prolonged release of antigen was noted from such combination formulations in comparison to release from PCEC nanoparticles alone; moreover, subcutaneous administration of combination systems to mice resulted in the production of potent and long-lived humoral immune responses, as well as indications of the induction of protective immunity (Wu et al 2011 ). A strong humoral immune response was also noted as a result of vaccination of mice with the aforementioned water-in-sorbitanmonostearate organogel, used in combination with haemagglutinin-loaded niosomes (non-ionic surfactant vesicles) (Murdan et al 1999b ).…”

<p>Virus-Like Particles Presenting the FGF-2 Protein or Identified Antigenic Peptides Promoted Antitumor Immune Responses in Mice</p>

“…40,41 Active immunization targeting FGF-2 is emerging as a promising strategy of anti-tumor angiogenesis. FGF-2 protein adjuvanted with a liposome-saponins formulation or loaded with biodegradable nanoparticles in thermosensitive hydrogel, or a N-and C-terminally truncated FGF-2 fragment adjuvanted with cationic liposome-DNA complex was reported, respectively, to successfully induce FGF-2 -specific antibody responses in mice and produced suppression on the growth and lung metastasis of B16 melanoma, 42 Lewis lung carcinoma, 43 or CT26 colonic carcinoma. 44 The studies used human-derived FGF-2 as antigen, which has high homogenicity with mouse FGF-2.…”

Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances

“…Examples of agents sensitive to such pH changes include polymers [15–17], pH sensitive nanogels [18, 19], as well as proteins critical to pathogen infection such as the hemagglutinin glycoprotein from influenza [20], listeriolysin [21], melittin [22], and many other viral proteins. These and many others have been creatively employed in a host of drug delivery strategies over the past several decades, with varying success.…”