Enhancing immunogenicity to PLGA microparticulate systems by incorporation of alginate and RGD-modified alginate

Abstract

Poly-lactide-co-glycolide acid (PLGA) and alginate represent two different families of polymers widely used for microencapsulation application, even more, for vaccination purposes as particulate delivery/adjuvant systems. Combination of these polymers has been previously considered for tissue engineering and drug delivery, however there is currently no report regarding their combination for vaccine application. In the present work, a w/o/w solvent extraction technique was developed to prepare novel 1 μm microparticles (MP) composed of PLGA and a small percentage of alginate (PLGA-alg MP). In addition, RGD-modified alginate was also employed as biofunctionalized material favoring MP–cell interaction (PLGA-alg-RGD MP). Two malaria synthetic peptides, SPf66 and S3, were microencapsulated into PLGA, PLGA-alg and PLGA-alg-RGD MP. The diverse MP formulations resulted very similar in terms of size and morphology, although the addition of alginate improved encapsulation efficiency and reduced the amount of surface adsorbed peptide. Immunization studies in Balb/c mice by intradermal route demonstrated that incorporation of alginate elicited higher humoral and cellular immune responses leading to more balanced Th1/Th2 responses. Furthermore, administration of MP containing RGD-modified alginate showed evidence of cell targeting by enhancing immunogenicity of microparticles, in particular with regard to cellular responses such as IFN-γ secretion and lymphoproliferation.