Loading of tetanus toxoid to biodegradable nanoparticles from branched poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide) nanoparticles by protein adsorption: a mechanistic study.
OBJECTIVE
Mucosal delivery of vaccine-loaded nanoparticles (NP) is an attractive proposition from an immunologic perspective. Although numerous NP preparation methods are known, sufficient antigen loading of NP remains a challenge. The aim of this study was to evaluate adsorptive loading of NP with a negatively charged surface structure using tetanus toxoid (TT) as a model vaccine.


METHODS
Blank NP, consisting of poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide), as well as poly(lactide-co-glycolide) NP were prepared by a solvent displacement technique. The use of polymers with different degrees of substitution resulted in NP with different negative surfaces charges. Adsorption of TT to NP was performed varying to NP surface properties, protein equilibrium concentration, and loading conditions.


RESULTS
The protein adsorption was controlled by NP surface properties, and maximum TT adsorption occurred at highly negatively charged NP surfaces. Results from isothermal titration calorimetry and zeta-potential measurement suggest an adsorption process governed by electrostatic interactions. The adsorption followed the Langmuir isotherm in the concentration ranges studied. TT withstood this gentle loading procedure in a nonaggregated, enzyme-linked immunoabsorbant assay-active form.


CONCLUSIONS
The results demonstrate that negatively charged NP consisting of poly(sulfobutyl-polyvinyl alcohol)-g-(lactide-co-glycolide) are suitable for adsorptive loading with TT and may have potential for mucosal vaccination.
Jung
Tobias
T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
Kamm
Walter
W
Breitenbach
Armin
A
Klebe
Gerhard
G
Kissel
Thomas
T
D000327:Adsorption / Q000187:drug effects; D036103:Nanotechnology / Q000379:methods*; D011098:Polyglactin 910 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011142:Polyvinyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000493:pharmacokinetics*
D011506:Proteins; D013745:Tetanus Toxoid; C413052:poly(2-sulfobutyl-vinyl alcohol)-graft-poly(lactide-co-glycolide); D011098:Polyglactin 910; D011142:Polyvinyl Alcohol