pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs

pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers’ dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption.

Drug release mechanisms from conventional and pH-sensitive nanoparticles. (A) Release from conventional nanoparticles by diffusion; (B) release from pH-sensitive nanoparticles after the materials dissolution at specific pH; (C) release from pH-sensitive nanomatrix by two steps, pH sensitive polymers dissolve first, a small part of drug released; then nano-porous silica exposed and drug embedded in the nano-pores diffused out of the pores; (D) release from pH-sensitive nanoparticles after the materials swelling at specific pH; and (E) release from pH-sensitive nanoparticles as the co-effect of dissolution and swelling of the materials at specific pH.Figure optionsDownload high-quality image (204 K)Download as PowerPoint slide