Oral drug administration has been regarded as the most convenient mode of drug administration because
avoidance of needle related pain, and non-sterile production requirements. Although oral delivery works well for
administration of small molecule oral delivery of macromolecules is very challenging. There are several barriers
associated with oral delivery of biological, particularly harsh environment associated with gastrointestinal tract
and low permeability across the intestinal epithelium. Most of the biological drugs approved for the clinical
use in last decade need to be administered by the parenteral route (injection or infusion). Parenteral
administration helps in achieving higher bioavailability but there are considerable disadvantages associated with
patient compliance and manufacturing requirements. It is crucial to design the smart drug delivery carriers to
overcome the several barriers faced by the oral delivery. Here, we tried to address the key challenges and
barriers associated with oral delivery of biologicals (Vaccine antigen, adjuvant and Gene) with engineered smart
carrier systems. We customized the carrier’s system accordingly need of the macromolecule to be delivered in a
safe and controlled manner at the specific site. We characterized the system, studied in-vitro effect with the help of in-vitro models closely mimicking the biological barriers. Finally, we studied the therapeutic effect of our
developed system with in-vivo mice model. We believe that, our system could be a promising carrier system for
the oral delivery of biological molecules and future clinical translation.