It depends on the route of administration. The PO is bioavailability dependent, the IV is solubility dependent. Both need stabilization in the final formulation form; in some cases for large molecules it could be the three dimensional structure of the molecule.
In several limited cases, sustained delivery of peptides and proteins has employed the use of polymeric carriers. More successes have been achieved by chemical modification using amino acid substitutions, protein pegylation or glycosylation to improve the pharmacodynamic properties of certain macromolecules.
proteins and peptides are large molecules with high molecular weights first problem would be its weight - ( if > 500 daltons difficult to permeate through cells - LIPINSKIS RULE )
second - Stability through oral or intravenous use - high rate for enzymatic degradation, before reaching the target site.
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