Optimization of stability, encapsulation, release, and cross-priming of tumor antigen-containing PLGA nanoparticles

Shashi Prasad, Virginia Cody, Jennifer K. Saucier-Sawyer, Tarek R. Fadel, Richard L. Edelson, Martin A. Birchall, Douglas J. Hanlon

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Purpose In order to investigate Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) as potential vehicles for efficient tumor antigen (TA) delivery to dendritic cells (DC), this study aimed to optimize encapsulation/release kinetics before determining immunogenicity of antigen-containing NP. Methods Various techniques were used to liberate TA from cell lines. Single (gp100) and multiple (B16-tumor lysate containing gp100) antigens were encapsulated within differing molecular weight PLGA co-polymers. Differences in morphology, encapsulation/ release and biologic potency were studied. Findings were adopted to encapsulate fresh tumor lysate from patients with advanced tumors and compare stimulation of tumor infiltrating lymphocytes (TIL) against that achieved by soluble lysate. Results Four cycles of freeze-thaw + 15 s sonication resulted in antigen-rich lysates without the need for toxic detergents or protease inhibitors. The 80KDa polymer resulted in maximal release of payload and favorable production of immunostimulatory IL-2 and IFN-?. NP-mediated antigen delivery led to increased IFN-? and decreased immunoinhibitory IL-10 synthesis when compared to soluble lysate. Conclusions Four cycles of freeze-thaw followed by 15 s sonication is the ideal technique to obtain complex TA for encapsulation. The 80KDa polymer has the most promising combination of release kinetics and biologic potency. Encapsulated antigens are immunogenic and evoke favorable TIL-mediated anti-tumor responses.

Original languageEnglish (US)
Pages (from-to)2565-2577
Number of pages13
JournalPharmaceutical Research
Volume29
Issue number9
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • Antigen delivery
  • Dendritic cell
  • Immunotherapy
  • Molecular weight
  • Nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

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    Prasad, S., Cody, V., Saucier-Sawyer, J. K., Fadel, T. R., Edelson, R. L., Birchall, M. A., & Hanlon, D. J. (2012). Optimization of stability, encapsulation, release, and cross-priming of tumor antigen-containing PLGA nanoparticles. Pharmaceutical Research, 29(9), 2565-2577. https://doi.org/10.1007/s11095-012-0787-4