pH- and ion-sensitive polymers for drug delivery.
BACKGROUND
Drug delivery systems (DDSs) are important for effective, safe, and convenient administration of drugs. pH- and ion-responsive polymers have been widely employed in DDS for site-specific drug release due to their abilities to exploit specific pH- or ion-gradients in the human body.


METHODS
Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(β-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations.


CONCLUSIONS
Stimuli-responsive DDSs are important for achieving site-specific and controlled drug release; however, intraindividual, interindividual and intercellular variations of pH should be considered when designing DDSs or drug products. Combination of polymers and other components, and deeper understanding of human physiology are important for development of pH- and ion-sensitive polymeric DDS products for patients.
Drug Delivery, Pharmaceutical Research and Technology Labs, Astellas Pharma, Inc. , 180 Ozumi, Yaizu, Shizuoka 425-0072 , Japan +81 54 627 6861 ; +81 54 627 9918 ; takayuki.yoshida@astellas.com.
Takayuki
T
Yoshida
Tsz Chung
TC
Lai
Glen S
GS
Kwon
Kazuhiro
K
Sako
D001682:Biological Availability; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D011108:Polymers / Q000737:chemistry*
D057846:Cell-Penetrating Peptides; D003692:Delayed-Action Preparations; D007477:Ions; D004364:Pharmaceutical Preparations; D011108:Polymers; C507253:poly(beta-amino ester)