Polyaminoacid-based nanocarriers: a review of the latest candidates for oral drug delivery.

The oral route is one of the most attractive modalities of drug delivery, providing easy administration and great patient compliance. However, enzymatic degradation and physiological barriers in the gastrointestinal tract are still unsolved obstacles for many drugs. The physico-chemical characteristics of biopharmaceuticals and the resulting low stability and poor penetration capacity across biological barriers represent current challenges that need to be overcome in oral delivery. The use of polyaminoacids and polypeptides, including cell-penetrating peptides as delivery carriers is an attractive strategy to improve the oral bioavailability of therapeutics. These biopolymers are positioned as potential biomaterials due to their low toxicity and their capacity to enhance the stability of biomolecules while increasing their transport through biological barriers. In this review, we present an update of the current approaches and strategies carried out in the design of nanosystems and penetration-enhancing oral delivery strategies based on polyaminoacids. Polyaminoacids and polypeptides are functional and versatile biomaterials which have received significant attention for the design of oral drug delivery platforms. Even though only a few prototypes have yet entered clinical trials, a number of promising strategies can be found in advanced preclinical investigation for the delivery of biopharmaceuticals.