Gastro-intestinal Tract

1. [Solution] Manipulate the primary sequence of protein

1.1. How

1.1.1. By recombinant technologies

1.2. Why

1.2.1. To reduce propensity to unfold in acidic media

1.2.2. To lower their susceptibility to peptin-mediated digestion

2. [Solution] Replacement of phenylalanine & leucine residues analogues

2.1. Less recognition by pepsin in stomach

2.2. Why

2.2.1. Phenylalanine & leucine were hydrolyzed by pepsin in stomach mechanisms

3. Problems

3.1. GI tract has low pH environment (pH 1 -2.5, involving peptidase

3.2. Enzymes are potentially difficult to stabilize at GI since GI is a primary digestion site for proteins

3.3. Enzymes can be inactivated in a harsh environment occurs in stomach

4. [Solution] Gastro-resistant, polymer-coated tablets/ microparticles can be used

4.1. How

4.1.1. Prepared with cellulose acetate phthalate/ methacrylate copolymer

4.2. Why

4.2.1. Keep away from stomach digestion & coatings so it can be dissolved at higher pH at small intestine

5. Covalent conjugation to polymer of GI enzymes

5.1. How

5.1.1. Steric shielding

5.2. Why

5.2.1. Provides protections