Self-encapsulating Poly(lactic-co-glycolic acid) (PLGA) Microspheres for Intranasal Vaccine Delivery

Mol Pharm. 2017 Sep 5;14(9):3228-3237. doi: 10.1021/acs.molpharmaceut.7b00586. Epub 2017 Aug 22.

Abstract

Herein we describe a formulation of self-encapsulating poly(lactic-co-glycolic acid) (PLGA) microspheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into premade PLGA microspheres. Calcium phosphate (CaHPO4) adjuvant gel was incorporated into the microspheres as a protein-trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 ± 0.31 μm, with a w/w loading of 0.60 ± 0.05% of ovalbumin (OVA) model antigen. The formulation demonstrated continuous release of OVA over a 49-day period. Released OVA maintained its antigenicity over the measured period of >21 days of release. C57BL/6 mice were immunized via the intranasal route with prime and booster doses of OVA (10 μg) loaded into microspheres or coadministered with cholera toxin B (CTB), the gold standard of mucosal adjuvants. Microspheres generated a Th2-type response in both serum and local mucosa, with IgG antibody responses approaching those generated by CTB. The results suggest that this formulation of self-encapsulating microspheres shows promise for further study as a vaccine delivery system.

Keywords: calcium phosphate adjuvant; encapsulation; intranasal immunization; poly(lactic-co-glycolic acid); polymer microspheres; vaccine delivery.

MeSH terms

  • Animals
  • Calcium Phosphates / chemistry
  • Cholera Toxin / chemistry
  • Chromatography, High Pressure Liquid
  • Drug Delivery Systems / methods
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Microspheres*
  • Ovalbumin / chemistry
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Vaccines / administration & dosage*
  • Vaccines / chemistry*

Substances

  • Calcium Phosphates
  • Vaccines
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Ovalbumin
  • Cholera Toxin
  • calcium phosphate