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Cited by 35Hydrogels: synthesis, properties, applicationsAdvanced Drug Delivery SystemsPolymer-Based Agricultural Enhancements

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

pH Responsive Hydrogels for the Delivery of Capecitabine: Development, Optimization and Pharmacokinetic Studies

Open access
Rehman, Umaira, Sarfraz, Rai Muhammad, Mahmood, Asif, Akbar, Shehla, E. Altyar, Ahmed, Khinkar, Roaa M., Gad, Heba A.·2022·Gels
DOI 10.3390/gels8120775PMC PMC9778381
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Abstract

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45–83.54% and 50.13–72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents.

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Crossref · 10.3390/gels8120775

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  • Cationic polymers like chitosan swell in pH media below pKb due to the protonation of cationic amine/imine group.

    “Cationic polymers like chitosan swell in pH media below pKb due to the protonation of cationic amine/imine group (Ding et al., 2022; Rehman et al., 2022).”

    From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Rehman et al., 2022

    The Introduction says chitosan is cationic and that protonation of its primary amine groups makes it soluble in dilute acid. Section 2.2 attributes expansion of the chitosan-containing hydrogel network to repulsion between ionized amino groups. The paper does not give a pKb threshold or attribute swelling below it to amine or imine protonation; its Conclusions instead report greater swelling of the tested hydrogels at alkaline than acidic pH. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Hydrogel formulations of chitosan and fenugreek-g-poly(MAA) showed a notable increase in swelling and in vitro drug release rate at pH 7.4 compared to pH 1.2, indicating pH-responsive nature.

    “The hydrogel formulations shown a notable increase in swelling and in vitro drug release rate when subjected to a pH of 7.4 compared to a pH of 1.2, thereby indicating the pH-responsive nature of the hydrogels.”

    From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Rehman et al., 2022

    Section 2.9 reports substantially greater in vitro capecitabine release at pH 7.4 than at pH 1.2. The Conclusions also state that swelling was greater at alkaline than acidic pH, but the swelling results in Section 2.2 report measurements at pH 7.4 without documenting a pH 1.2 comparison. Thus, the specific pH 7.4-versus-1.2 comparison is supported for drug release, but not established for swelling. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The swelling percentage and capecitabine loading of the hydrogels ranged from 74.45%-83.54% and 50.13%-72.43%, respectively.

    “The swelling percentage and CAP loading exhibited a range of 74.45%–83.54% and 50.13%–72.43%, respectively.”

    From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Rehman et al., 2022

    Section 2.1 (CAP Loading) reports the claimed loading range of 50.13–72.43%. Section 2.2 (Swelling Behavior) instead reports swelling values spanning 70.37–90.62% across the formulations, so the claimed swelling range of 74.45–83.54% is not supported. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • There were no observed indications of oral, cutaneous, or ocular toxicities for the improved hydrogel formulation, confirming its safety profile.

    “There were no observed indications of oral, cutaneous, or ocular toxicities, hence providing confirmation of the network’s safety profile.”

    From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Rehman et al., 2022

  • Pharmacokinetic research revealed sustained release of capecitabine from hydrogels, with elevated plasma half-life (13 h) and AUC (42.88 μg h/mL).

    “In addition, the pharmacokinetic research revealed the sustained release properties of capecitabine from hydrogels, as evidenced by a notable elevation in the plasma half-life (t1/2) (13 h) and the area under the curve (AUC) (42.88 μg h/mL) of capecitabine.”

    From pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. (2023) · cites this paper as Rehman et al., 2022

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Metadata

Authors
Rehman, U., Sarfraz, R. M., Mahmood, A., Akbar, S., E. Altyar, A., Khinkar, R. M., & Gad, H. A.
Affiliations
  • University of Sargodha (PK)
  • University of Chakwal (PK)
  • University of the Punjab (PK)
  • Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia
  • King Abdulaziz University (SA)
  • Ain Shams University (EG)
Corresponding author
Gad, Heba A.
ORCID
Venue
Gels
Publisher
MDPI AG
Published
2022-11-28
Volume
8
Issue
12
Pages
775
ISSN
2310-2861 (ISSN-L)
DOI
10.3390/gels8120775
PMC
PMC9778381
OpenAlex
W4310171889
Cited by
33
References
39
Citations by year
2026: 9 · 2025: 12 · 2024: 6 · 2023: 6
FWCI
1.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Gels (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia (RG-23-166-43)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Polymer-Based Agricultural Enhancements
Keywords
capecitabine, pH-responsive hydrogels, chitosan, fenugreek gum, poly(maleic anhydride), controlled drug release, sustained drug release, oral drug delivery, pharmacokinetics, acute oral toxicity, colorectal cancer, swelling behavior, drug loading

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