Novel Protein Core-shell Nanoparticles for Oral Drug Delivery

Oral route is the most common and convenient route for drug administration. Various factors govern oral drug absorption including solubility, mucosal permeability, and stability in the gastrointestinal tract environment. To this end, there is a need to develop novel drug carriers for oral administration of poorly bioavailable drugs. Food based proteins are generally regarded as safe and offer many benefits for developing oral formulations, especially for pediatric patients. The main goal of this research is to develop core-shell NPs using protein biopolymers. Zein, a hydrophobic corn protein was used as the core, while milk proteins (β-casein or lactoferrin) or polyethylene glycol (PEG) were used as the shell. The NPs were prepared by phase separation. A lipophilic fluorescent dye, Nile Red was used as a model compound. In vitro Caco-2 cells studies demonstrated that zein core-shell NPs increased cell uptake and enhanced the permeability of Nile Red. The second goal was to study the use of the NPs for oral delivery of All-trans-retinoic acid, a BCS class II. The size of ATRA loaded NPs was below 200nm, and the encapsulation efficiency was more than 90%. The in vitro release of ATRA was evaluated in milk and apple juice to test the feasibility of administering the NPs in a food matrix for pediatric patients. The NPs were stable in milk and apple juice, and it sustained the drug release in gastrointestinal fluids. In vivo pharmacokinetic studies showed that the NPs enhanced the oral bioavailability of ATRA. The last objective was to study the use of the NPs for the oral delivery of saquinavir, an anti-viral drug with poor solubility and permeability, a BCS (class IV). The NPs protected the SQ in milk and apple juice and the drug was released in a sustained fashion in simulated gastric and intestinal fluids. SQ-NPs showed higher permeability through the Caco-2 cell monolayer in comparison to free SQ. In vivo pharmacokinetic studies showed that the NPs enhanced the oral bioavailability of SQ. Overall, these results demonstrate that the zein based core-shell NPs are potential nanocarriers to increase the oral bioavailability of drugs, especially for pediatric patients