Positional Isomerism Influences pH-Responsive Release Kinetics in Methacryloyloxybenzoic Acid Polymeric Prodrugs
- 1Faculty of Chemical Sciences and Engineering, Autonomous University of Baja California, University Boulevard No. 14418, Otay Mesa, Tijuana 22390, Mexico
- 2Faculty of Health Sciences, Autonomous University of Baja California, 1000 University Boulevard, Valle de Las Palmas, Tijuana 22260, Mexico
Abstract
Polymeric prodrugs capable of pH-responsive drug release are promising platforms for localized and controlled drug delivery. While positional isomerism is known to affect the physicochemical properties of MBA polymers, a comparative evaluation of its effect on drug release kinetics and biological activity is lacking. In this study, three methacryloyloxybenzoic acid (MBA) polymeric prodrugs derived from ortho-, meta-, and para-hydroxybenzoic acid (HBA) isomers were synthesized to comparatively evaluate the influence of substituent position on HBA release profiles and biological performance. The o-, m-, and p-MBA monomers and their corresponding polymers were synthesized and structurally characterized by FTIR-ATR, 1H-NMR and UV-Vis spectroscopy. HBA release profiles investigated under physiologically relevant pH conditions revealed markedly distinct release profiles among the polymers. Poly(o-MBA) exhibited rapid and near-complete release at intestinal and physiological pH, poly(p-MBA) showed sustained and intermediate release, and poly(m-MBA) displayed minimal release under all tested conditions, indicating that substituent position strongly influences HBA release, likely through differences in ester accessibility and hydrolytic susceptibility. The polymers also exhibited planktonic antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, while BALB/3T3 fibroblast viability remained above 70% at a concentration of 0.5 mg/mL. These findings indicate that positional isomerism is a key structural determinant of pH-responsive release kinetics in MBA polymers and highlight their potential as versatile platforms for pharmaceutical and biomedical applications, particularly in the design of localized and controlled drug delivery systems.
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BibTeX
@article{vazquezestudillo2026positional,
title = {{Positional Isomerism Influences pH-Responsive Release Kinetics in Methacryloyloxybenzoic Acid Polymeric Prodrugs}},
author = {Hebrón Vázquez-Estudillo and Giovanni Palomino-Vizcaino and Brisa G. Hernández-Ramírez and Lilia A. Hurtado-Ayala and Jonathan Vincent Lopez-Baena and Teresa G. Rodriguez-Tellez and Iván Cordova-Guerrero and Lucia E. Azuara-Alvarez and Arturo Estolano-Cobián and Kenia Palomino-Vizcaino and José M. Cornejo-Bravo and Héctor Magaña},
journal = {Polymers},
year = {2026},
month = nov,
doi = {10.3390/polym18212789},
url = {https://www.mdpi.com/2073-4360/18/21/2789},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Positional Isomerism Influences pH-Responsive Release Kinetics in Methacryloyloxybenzoic Acid Polymeric Prodrugs
AU - Hebrón Vázquez-Estudillo
AU - Giovanni Palomino-Vizcaino
AU - Brisa G. Hernández-Ramírez
AU - Lilia A. Hurtado-Ayala
AU - Jonathan Vincent Lopez-Baena
AU - Teresa G. Rodriguez-Tellez
AU - Iván Cordova-Guerrero
AU - Lucia E. Azuara-Alvarez
AU - Arturo Estolano-Cobián
AU - Kenia Palomino-Vizcaino
AU - José M. Cornejo-Bravo
AU - Héctor Magaña
PY - 2026
DA - 2026/11/08
JO - Polymers
DO - 10.3390/polym18212789
UR - https://www.mdpi.com/2073-4360/18/21/2789
AB - Polymeric prodrugs capable of pH-responsive drug release are promising platforms for localized and controlled drug delivery. While positional isomerism is known to affect the physicochemical properties of MBA polymers, a comparative evaluation of its effect on drug release kinetics and biological activity is lacking. In this study, three methacryloyloxybenzoic acid (MBA) polymeric prodrugs derived from ortho-, meta-, and para-hydroxybenzoic acid (HBA) isomers were synthesized to comparatively evaluate the influence of substituent position on HBA release profiles and biological performance. The o-, m-, and p-MBA monomers and their corresponding polymers were synthesized and structurally characterized by FTIR-ATR, 1H-NMR and UV-Vis spectroscopy. HBA release profiles investigated under physiologically relevant pH conditions revealed markedly distinct release profiles among the polymers. Poly(o-MBA) exhibited rapid and near-complete release at intestinal and physiological pH, poly(p-MBA) showed sustained and intermediate release, and poly(m-MBA) displayed minimal release under all tested conditions, indicating that substituent position strongly influences HBA release, likely through differences in ester accessibility and hydrolytic susceptibility. The polymers also exhibited planktonic antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, while BALB/3T3 fibroblast viability remained above 70% at a concentration of 0.5 mg/mL. These findings indicate that positional isomerism is a key structural determinant of pH-responsive release kinetics in MBA polymers and highlight their potential as versatile platforms for pharmaceutical and biomedical applications, particularly in the design of localized and controlled drug delivery systems.
SN - 2073-4360
ER -