pH- and ion-sensitive polymers for drug delivery

Yoshida, Takayuki; Lai, Tsz Chung; Kwon, Glen S; Sako, Kazuhiro

doi:10.1517/17425247.2013.821978

Cited by 367Advanced Drug Delivery SystemsHydrogels: synthesis, properties, applicationsNanoparticle-Based Drug Delivery

pH- and ion-sensitive polymers for drug delivery

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Yoshida, Takayuki, Lai, Tsz Chung, Kwon, Glen S, Sako, Kazuhiro·2013·Expert Opinion on Drug Delivery

DOI 10.1517/17425247.2013.821978PMC PMC3912992

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Abstract

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

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Basic pH-responsive polymers such as albumin and PAA swell in basic pH and shrink in acidic pH.
“where the basic pH-responsive polymers such as albumin and polyacrylic acid (PAA) swell in basic pH and shrink in acidic pH [41,42].”
From Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application (2019) · cites this paper as [42]
Section 2.2, ‘Polymers responsive to intestinal high pH’ (page not provided), says that anionic polymers with carboxyl groups are more water-soluble at basic than acidic pH. It does not say they swell and shrink, or identify albumin and polyacrylic acid (PAA) as examples of that behavior; its mention of albumin is as a microsphere payload. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Cationic pH-responsive polymers including chitosan, PDMAEMA, and PDEAEMA swell in acidic pH and shrink in basic pH.
“The cationic pH responsive polymers including chitosan, poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), and poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) swell in acidic pH and shrink in basic pH”
From Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application (2019) · cites this paper as [42]
Section 2.1 says cationic polymers with amino groups are more soluble at acidic than at higher pH, and section 2.2 identifies chitosan as cationic. Section 2.4 identifies poly(2-(dimethylamino)ethyl methacrylate) as cationic. These passages support the general direction of pH responsiveness, but they do not establish that the named polymers swell in acid and shrink in base; the copy does not identify PDEAEMA in this claim. (LLM, conf=0.83)
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“The cationic pH responsive polymers including chitosan, poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), and poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) swell in acidic pH and shrink in basic pH, where the basic pH-responsive polymers such as albumin and polyacrylic acid (PAA) swell in basic pH and shrink i…”
Background
A comprehensive review on doxorubicin: mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer
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pH-Triggered Polypeptides Nanoparticles for Efficient BODIPY Imaging-Guided Near Infrared Photodynamic Therapy
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Authors: Yoshida, T., Lai, T. C., Kwon, G. S., & Sako, K.
Affiliations: Astellas Pharma (Japan) (JP)
University of Wisconsin–Madison (US)
Corresponding author: Yoshida, Takayuki
ORCID: Yoshida, Takayuki
Lai, Tsz Chung
Kwon, Glen S
Venue: Expert Opinion on Drug Delivery
Publisher: Informa UK Limited
Published: 2013-08-09
Volume: 10
Issue: 11
Pages: 1497-1513
ISSN: 1742-5247 (ISSN-L)
1744-7593
DOI: 10.1517/17425247.2013.821978
PMC: PMC3912992
OpenAlex: W2003276331
Cited by: 367
References: 112
Citations by year: 2026: 22 · 2025: 40 · 2024: 40 · 2023: 45 · 2022: 26 · 2021: 32 · 2020: 31 · 2019: 35 · 2018: 38 · 2017: 17 · 2016: 20 · 2015: 14 · 2014: 6
FWCI: 1.68
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Expert Opinion on Drug Delivery (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R01AI101157)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords: pH-responsive polymers, site-specific drug release, cationic polymers, taste masking, colon-targeted drug delivery, anticancer drug delivery, poly(β-amino ester), hydrazone linkage, cell-penetrating peptides, ion exchange resins, sustained drug release, oral drug formulation, gastric pH, intracellular drug delivery
MeSH terms: Biological Availability, Chemistry, Pharmaceutical, Delayed-Action Preparations, Pharmaceutical Preparations, Humans, Hydrogen-Ion Concentration, Ions, Polymers, Drug Delivery Systems, Cell-Penetrating Peptides

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