Beta-lactoglobulin (BLG)-derived
peptides may facilitate oral tolerance to whey and prevent
cow's milk allergy (CMA). Loading of BLG-
peptides in
poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Pep-NP) may improve this. Here we studied the uptake of NP and the capacity of NP and Pep-NP to activate bone marrow dendritic cells (BMDC). Furthermore, CMA prevention was evaluated by orally exposing three-week-old female C3H/HeOuJ mice to Pep-NP, NP or free
peptides (PepMix) for 6 days before oral sensitization with whole
whey protein and effects on the spleen and small intestine lamina propria (SI-LP) were studied. In BMDC, NP and Pep-NP enhanced CD40 expression and
IL-6 and TNF-α secretion, while tended to decrease CD80 expression and prevented PepMix-induced
IL-12 secretion. In vivo, oral exposure to Pep-NP, but not NP or PepMix, prior to whey sensitization tended to partially prevent the acute allergic skin response to whole
whey protein. Splenocytes of NP-pre-exposed mice secreted increased levels of whey-specific
IL-6, but this was silenced in Pep-NP-pre-exposed mice which also showed reduced TNF-α and IFN-γ secretion. In the SI-LP, Pep-NP pre-exposure reduced the CD4+ T cell frequency in CMA mice compared to PBS pre-exposure. In addition, while NP increased whey-specific
IL-6 secretion in the SI-LP, Pep-NP did not and maintained regulatory TGF-β secretion. This study presents a proof-of-concept that PLGA nanoparticles facilitate the capacity of BLG
peptides to suppress the allergic response to whole
whey protein. Hence, PLGA nanoparticles may be further developed as an adjunct strategy for BLG-
peptide-based oral tolerance induction and CMA prevention.