Table 1.

Mechanisms of pH-sensitive drug delivery systems.

Mechanism	Species	Functions	Refs.
Ionizable chemical groups	Amines, phosphoric acids, carboxylic acids, acylsulfonamide	i. Molecular conformation change ii. Drug release iii. Positive charge	[75, 77, 95]
Acid-labile chemical bonds	Acetal, orthoester, hydrazone, imine, cis-aconyl	i. Hydrolytic cleavage ii. Size shrinking iii. Drug release iiii. Ligand re-emergence	[62, 177, 187]
pH-responsive polymer	Anionic polymers containing carboxylic groups (PAA, PMAA, PEAA, PPAA, PBAA, NIPAM, and PGA), and sulfonamide groups	i. Drug release	[189-190]
pH-responsive polymer	Cationic polymers containing tertiary amine groups, pyridine groups and imidazole groups	i Drug release ii. Positive charge iii. Proton sponge	[76, 85, 86, 118]
pH-sensitive peptide	GALA, pHLIP, histidine-containing acidic pH-activated cell-penetrating peptides	i. Molecular conformation change ii. Cell penetration	[155, 191]
Incorporate carbon dioxide-generating precursors	Sodium bicarbonate, ammonium bicarbonate	i. Carbon dioxide generation ii. Drug release	[132, 133]