Mannose-Modified PLGA Nanoparticles for Sustained and Targeted Delivery in Hepatitis B Virus Immunoprophylaxis

Abstract

The launched hepatitis B vaccine could induce powerful antibodies, whereas it failed to improve potent cellular immune responses due to that the Th2-type response-induced aluminum adjuvant was adopted. Here, to target antigen-presenting cells under the epidermis and induce potent cellular and humoral immune responses, mannose-modified poly d,l-lactide-co-glycolic acid (PLGA) was synthesized and nanoparticle (MNP)-loaded hepatitis B surface antigen (HBsAg) protein was prepared. HBsAg could be slowly released and highly presented to lymphocytes which facilitated to produce long-lasting immunity based on characters of PLGA. In vitro uptake test results showed that MNPs could enhance internalization in bone marrow–derived dendritic cells (BMDCs) and RAW 264.7 cells. Subcutaneous delivery of MNPs into mice kept humoral immune and strengthened cellular immune responses. Experimental results indicated that MNPs showed significantly modified properties compared with parental PLGA nanoparticles. Thus, the obtained MNPs could be a promising vehicle for hepatitis B vaccine delivery.

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Acknowledgments

We thank Gillian Campbell, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Funding

This study was supported by Science and Technology Department of Zhejiang province public welfare technology research project (Grant No. 2015C31100), Key Laboratory of Ningbo, China (No. 2016A22002), and National Natural Science Foundation of China (Grant Nos. 81173000, 81873838).

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Correspondence to Ying Hu or Caihong Zheng.

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Animal experiments were approved by the experimental animal ethics committee of Zhejiang University (ZJU20160200) in the animal experimentation section.

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Zhu, J., Qin, F., Ji, Z. et al. Mannose-Modified PLGA Nanoparticles for Sustained and Targeted Delivery in Hepatitis B Virus Immunoprophylaxis. AAPS PharmSciTech 21, 13 (2020). https://doi.org/10.1208/s12249-019-1526-5

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KEY WORDS

  • PLGA
  • mannose-modificated
  • target
  • hepatitis B surface antigen
  • immunoprophylaxis