pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release

Hoti, Gjylije; Er-Rahmani, Sara; Gatti, Alessia; Hussein, Ibrahim; Argenziano, Monica; Cavalli, Roberta; Anceschi, Anastasia; Matencio, Adrián; Trotta, Francesco; Caldera, Fabrizio

doi:10.3390/gels12010090

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release

by

Gjylije Hoti

^1,2,†

,

Sara Er-Rahmani

^1,†,

Alessia Gatti

²,

Ibrahim Hussein

^1,2

,

Monica Argenziano

²

,

Roberta Cavalli

²

,

Anastasia Anceschi

¹

,

Adrián Matencio

³

,

Francesco Trotta

^1,*

and

Fabrizio Caldera

¹

Department of Chemistry, NIS Interdepartmental Centre, University of Turin, Via P. Giuria 7, 10125 Turin, Italy

²

Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10125 Turin, Italy

³

Biology Teaching Unit, Department of Biochemistry and Molecular Biology A, Faculty of Veterinary Medicine, Regional Campus of International Excellence “Campus Mare Nostrum”, University of Murcia, 30100 Murcia, Spain

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Gels 2026, 12(1), 90; https://doi.org/10.3390/gels12010090 (registering DOI)

Submission received: 1 November 2025 / Revised: 11 January 2026 / Accepted: 12 January 2026 / Published: 19 January 2026

(This article belongs to the Special Issue Functional Gel Materials: Chemistry, Processing, Mechanical Performance, and Applications)

Download

Browse Figure

Versions Notes

Abstract

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions.

Keywords: dextrin; nanosponges; hydrogels; pH-sensitive swelling; Flory–Rehner theory; rheology; mucoadhesion capacity

Graphical Abstract

Share and Cite

MDPI and ACS Style

Hoti, G.; Er-Rahmani, S.; Gatti, A.; Hussein, I.; Argenziano, M.; Cavalli, R.; Anceschi, A.; Matencio, A.; Trotta, F.; Caldera, F. pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release. Gels 2026, 12, 90. https://doi.org/10.3390/gels12010090

AMA Style

Hoti G, Er-Rahmani S, Gatti A, Hussein I, Argenziano M, Cavalli R, Anceschi A, Matencio A, Trotta F, Caldera F. pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release. Gels. 2026; 12(1):90. https://doi.org/10.3390/gels12010090

Chicago/Turabian Style

Hoti, Gjylije, Sara Er-Rahmani, Alessia Gatti, Ibrahim Hussein, Monica Argenziano, Roberta Cavalli, Anastasia Anceschi, Adrián Matencio, Francesco Trotta, and Fabrizio Caldera. 2026. "pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release" Gels 12, no. 1: 90. https://doi.org/10.3390/gels12010090

APA Style

Hoti, G., Er-Rahmani, S., Gatti, A., Hussein, I., Argenziano, M., Cavalli, R., Anceschi, A., Matencio, A., Trotta, F., & Caldera, F. (2026). pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release. Gels, 12(1), 90. https://doi.org/10.3390/gels12010090

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Article metric data becomes available approximately 24 hours after publication online.

Article Menu

pH-Sensitive Dextrin-Based Nanosponges Crosslinked with Pyromellitic Dianhydride and Citric Acid: Swelling, Rheological Behavior, Mucoadhesion, and In Vitro Drug Release

Abstract

Share and Cite

Article Metrics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI