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Autores principales: Khan, Tehsin Ullah, Mushtaq, Nadia, Iqbal, Tahir, Liu, Chen-Guang
Formato: Artículo científico
Lenguaje:en
Publicado: International journal of pharmaceutics 2026
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Acceso en línea:https://pubmed.ncbi.nlm.nih.gov/41241163/
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author Khan, Tehsin Ullah
Mushtaq, Nadia
Iqbal, Tahir
Liu, Chen-Guang
author_facet Khan, Tehsin Ullah
Mushtaq, Nadia
Iqbal, Tahir
Liu, Chen-Guang
Khan, Tehsin Ullah
Mushtaq, Nadia
Iqbal, Tahir
Liu, Chen-Guang
collection PubMed - marine biology
contents Mucoadhesive hyaluronic acid composites for prolonged gastric retention. Khan, Tehsin Ullah Mushtaq, Nadia Iqbal, Tahir Liu, Chen-Guang Hyaluronic Acid Gastric Mucosa Humans Animals Mucins Drug Delivery Systems Adhesiveness The interaction between mucoadhesive materials and the mucin layer is a critical factor in the development of advanced drug delivery systems designed to enhance site-specific targeting and prolong gastrointestinal residence time. Among these materials, hyaluronic acid (HA), a naturally occurring, linear glycosaminoglycan composed of repeating disaccharide units of β(1 → 3)-D-glucuronic acid and β(1 → 4)-N-acetyl-D-glucosamine, has emerged as a promising mucoadhesive agent due to its unique physicochemical properties. Despite the inherent electrostatic repulsion between the anionic carboxylate groups (-COO) of HA and the negatively charged sialic acid residues on mucin glycoproteins, HA achieves strong mucoadhesion through a combination of non-electrostatic interactions. These include: (1) hydrogen bonding between the hydroxyl (-OH) and protonated carboxyl (-COOH) groups of HA and functional groups such as hydroxyl, amide, and carboxyl groups on mucin; (2) physical entanglement of HA's flexible polymeric chains within the mucin network; (3) hydration-mediated cohesion driven by HA's high water retention capacity and hydrogel-forming nature; and (4) van der Waals forces at hydrophobic domains within the mucin layer. HA exhibits shear-thinning rheological behavior and molecular weight-dependent viscosity, which are advantageous for mucoadhesion, particularly under the acidic conditions of the gastric environment. Moreover, HA-based composites, including chitosan-HA hybrids, nanoparticles, and hydrogel systems, demonstrate enhanced mucosal adhesion and penetration through mechanisms such as steric stabilization and improved tissue interaction. These effects have been validated by a range of analytical techniques, including rheological measurements, atomic force microscopy (AFM), and in vivo imaging modalities. HA has been successfully utilized in the development of pH-responsive delivery platforms for antibiotics and gastroprotective agents, resulting in improved gastric retention and therapeutic efficacy. To overcome physiological challenges such as rapid mucus turnover (approximately every 4-6 h), current research focuses on engineering stimuli-responsive systems, mucopenetrating nanoparticles, and employing three-dimensional (3D) bioprinted mucosal models to optimize drug delivery. Looking ahead, innovations integrating high-throughput omics technologies and scalable manufacturing approaches hold great promise for the development of next-generation HA-based therapeutics. These advancements position HA as a cornerstone for precision-targeted therapies for gastric ulcers, inflammation, and other gastrointestinal disorders. This review critically examines mucoadhesive mechanisms and compares HA derivatives' gastric-retention and mucoadhesive performance, showing how specific modifications produce measurable improvements.
format Artículo científico
id pubmed_41241163
institution PubMed
language en
publishDate 2026
publisher International journal of pharmaceutics
record_format pubmed
spellingShingle Mucoadhesive hyaluronic acid composites for prolonged gastric retention.
Khan, Tehsin Ullah
Mushtaq, Nadia
Iqbal, Tahir
Liu, Chen-Guang
Hyaluronic Acid
Gastric Mucosa
Humans
Animals
Mucins
Drug Delivery Systems
Adhesiveness
Mucoadhesive hyaluronic acid composites for prolonged gastric retention. Khan, Tehsin Ullah Mushtaq, Nadia Iqbal, Tahir Liu, Chen-Guang Hyaluronic Acid Gastric Mucosa Humans Animals Mucins Drug Delivery Systems Adhesiveness The interaction between mucoadhesive materials and the mucin layer is a critical factor in the development of advanced drug delivery systems designed to enhance site-specific targeting and prolong gastrointestinal residence time. Among these materials, hyaluronic acid (HA), a naturally occurring, linear glycosaminoglycan composed of repeating disaccharide units of β(1 → 3)-D-glucuronic acid and β(1 → 4)-N-acetyl-D-glucosamine, has emerged as a promising mucoadhesive agent due to its unique physicochemical properties. Despite the inherent electrostatic repulsion between the anionic carboxylate groups (-COO) of HA and the negatively charged sialic acid residues on mucin glycoproteins, HA achieves strong mucoadhesion through a combination of non-electrostatic interactions. These include: (1) hydrogen bonding between the hydroxyl (-OH) and protonated carboxyl (-COOH) groups of HA and functional groups such as hydroxyl, amide, and carboxyl groups on mucin; (2) physical entanglement of HA's flexible polymeric chains within the mucin network; (3) hydration-mediated cohesion driven by HA's high water retention capacity and hydrogel-forming nature; and (4) van der Waals forces at hydrophobic domains within the mucin layer. HA exhibits shear-thinning rheological behavior and molecular weight-dependent viscosity, which are advantageous for mucoadhesion, particularly under the acidic conditions of the gastric environment. Moreover, HA-based composites, including chitosan-HA hybrids, nanoparticles, and hydrogel systems, demonstrate enhanced mucosal adhesion and penetration through mechanisms such as steric stabilization and improved tissue interaction. These effects have been validated by a range of analytical techniques, including rheological measurements, atomic force microscopy (AFM), and in vivo imaging modalities. HA has been successfully utilized in the development of pH-responsive delivery platforms for antibiotics and gastroprotective agents, resulting in improved gastric retention and therapeutic efficacy. To overcome physiological challenges such as rapid mucus turnover (approximately every 4-6 h), current research focuses on engineering stimuli-responsive systems, mucopenetrating nanoparticles, and employing three-dimensional (3D) bioprinted mucosal models to optimize drug delivery. Looking ahead, innovations integrating high-throughput omics technologies and scalable manufacturing approaches hold great promise for the development of next-generation HA-based therapeutics. These advancements position HA as a cornerstone for precision-targeted therapies for gastric ulcers, inflammation, and other gastrointestinal disorders. This review critically examines mucoadhesive mechanisms and compares HA derivatives' gastric-retention and mucoadhesive performance, showing how specific modifications produce measurable improvements.
title Mucoadhesive hyaluronic acid composites for prolonged gastric retention.
topic Hyaluronic Acid
Gastric Mucosa
Humans
Animals
Mucins
Drug Delivery Systems
Adhesiveness
url https://pubmed.ncbi.nlm.nih.gov/41241163/