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AAPS PharmSciTech

, Volume 19, Issue 3, pp 1160–1167 | Cite as

Combined Poly(Lactide-Co-Glycolide) Microspheres Containing Diphtheria Toxoid for a Single-shot Immunization

  • Hye Seung Woo
  • Sung Rae Kim
  • Mikyeong Yoon
  • Eun Seok Lee
  • In Ho Chang
  • Young Mi Whang
  • Do Ik Lee
  • Myung Joo Kang
  • Young Wook Choi
Research Article

Abstract

To develop a single-shot vaccine containing diphtheria toxoid (DT) with a sufficient immune response, poly(lactide-co-glycolide) (PLGA) microspheres were prepared by water-in-oil-in-water double emulsification and solvent extraction techniques using low or high-molecular-weight PLGA (LMW-MS or HMW-MS). Stearic acid (SA) was introduced to HMW-MS (HMW/SA-MS) as a release modulator. Mean particle sizes (dvs, μm) varied between the prepared microspheres, with LMW-MS, HMW-MS, and HMW/SA-MS having the sizes of 29.83, 110.59, and 69.5 μm, respectively; however, the protein entrapment and loading efficiency did not vary, with values of 15.2–16.8 μg/mg and 61–75%, respectively. LMW-MS showed slower initial release (~ 2 weeks) but faster and higher release of antigen during weeks 3~7 than did HMW-MS. HMW/SA-MS showed rapid initial release followed by a continuous release over an extended period of time (~ 12 weeks). Mixed PLGA microspheres (MIX-MS), a combination of HMW/SA-MS and LMW-MS (1:1), demonstrated a sufficient initial antigen release and a subsequent boost release in a pulsatile manner. Serum antibody levels were measured by ELISA after DT immunization of Balb/c mice, and showed a greater response to MIX-MS than to alum-adsorbed DT (control). A lethal toxin challenge test with MIX-MS (a DT dose of 18 Lf) using Balb/c mice revealed complete protection, indicating a good candidate delivery system for a single-shot immunization.

KEY WORDS

PLGA single-shot vaccine diphtheria toxoid stearic acid immunization 

Notes

Funding Information

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0710).

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Hye Seung Woo
    • 1
  • Sung Rae Kim
    • 1
  • Mikyeong Yoon
    • 1
  • Eun Seok Lee
    • 1
  • In Ho Chang
    • 2
  • Young Mi Whang
    • 2
  • Do Ik Lee
    • 1
  • Myung Joo Kang
    • 3
  • Young Wook Choi
    • 1
  1. 1.College of PharmacyChung-Ang UniversitySeoulSouth Korea
  2. 2.Colleg of MedicineChung-Ang UniversitySeoulSouth Korea
  3. 3.College of PharmacyDankook UniversityCheonanSouth Korea

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