Short beta-lactoglobulin-derived peptides loaded in PLGA nanoparticles for the prevention of cow's milk allergy

Introduction: Poly(lactic-co-glycolic acid) (PLGA) is a safe and biodegradable polymer suitable for mucosal antigen delivery. Betalactoglobulin (BLG)-derived peptides might provide an alternative for the intact antigen in cow's milk allergy prevention strategies for atrisk infants. PLGA-nanoparticles can protect BLG-peptides from enzymatic degradation and ensure their sustained release and processing by dendritic cells (DC) after oral administration. Objectives: The current study investigated the effect of PLGA encapsulation of BLG-peptides on their capacity to prevent the allergic response to whey protein. Methods: Short synthetic BLG-peptides were encapsulated in PLGA nanoparticles via a double emulsion method. Bone-marrow-derived DC (BMDC) were stimulated in vitro with empty PLGA nanoparticles (NP), a mixture of free peptides (PepMix) or a mixture of encapsulated peptides (Pep-NP). Three-week-old female C3H/HeOuJ mice were administered NP, PepMix or Pep-NP orally for 6 days before oral sensitization with whey protein and cholera toxin as an adjuvant. Acute allergic skin response was evaluated after intradermal injection with whey. 18 hours After an oral challenge with whey, mice were euthanized and splenocytes and small intestine lamina propria (SI-LP) cells were isolated. Whey-induced cytokine production was evaluated after 5 days of ex vivo re-exposure to whey. Results: In vitro stimulation of BMDC with either NP or Pep-NP increased CD40 (P