Spray congealed lipid microparticles for the local delivery of β-galactosidase to the small intestine.

Oral local delivery of therapeutic biologics is generally limited due to the multiple obstacles of the gastrointestinal (GI) tract, mainly represented by acidic stomach pH and digestive enzymes. In the present study, spray congealing was used to prepare solid lipid microparticles (SLMs) loaded with β-galactosidase (lactase), an enzyme used for the treatment of lactose intolerance, to achieve a local drug delivery to the small intestine. Lactase was characterized in terms of activity at different pH, kinetic parameters and proteolytic degradation by digestive enzymes. Then, five lipid excipients were used to prepare unloaded SLMs, which were tested regarding lipase-induced digestion. The lipid with the best performance (glyceryl trimyristate) was used to prepare lactase-loaded SLMs. Spray congealed SLMs were spherical with very good encapsulation efficiency (>95%). The ability of the SLMs to protect the enzyme from the degradation in gastric environment was correlated with the particle size and the best formulation preserved the lactase activity up to 70%. Lactase was promptly released in simulated intestinal environment, and an in vitro positive food effect was observed. The present study demonstrated the potential of spray congealing for the preparation of solid lipid formulations able to achieve local oral delivery of a biologic drug.