The drug release from the pH-sensitive nanoparticles follows certain mechanisms which include: 1- Drug burst releases when the nanoparticle carriers dissolve at specific pH conditions: They usually exhibited burst release profiles because of the dissolution characters of the carriers; drug release from conventional nanoparticles was mainly by diffusion. For pH- sensitive nanoparticles, at low pH, the nanoparticles prepared from polycarboxylic acid were solid matrix encapsulating drug, little drug released. As they reach the small intestine, the pH changes from acidic to neutral (6–7.4), carboxylic acid groups deprotonated, the linear polymers dissolved and drugs released rapidly. 2- Drug releases when the polymers swell at specific pH conditions: Another reason for drug release from nanoparticles was the swelling of the materials [96]. At low pH, the polymers, particularly cross-linked polymers, have a compact structure, which considerably decreased the porosity of the matrix. This caused a slower release of drug as a result of the greater resistance for diffusion of the drug out of the nanogel. However, at higher pH, the nanogel particles were in a swollen state with a higher porosity that favored the release of the drug because of the reduction in diffusion resistance. 3- The drug releases as a result of both polymer dissolution and swelling: There was obscure boundary between drug dissolution and swelling for the carriers. Some nanoparticle systems might release drug through both the mechanisms. Li et al., 2006 [97] studied the release of insulin from chitosan–Eudragit L100-55 nanoparticles in vitro. The results proposed that at low pH, the nanoparticles were covered by Eudragit L100-55, little water permeated into the particles a>