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ORIGINAL RESEARCH
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Glutaraldehyde-cross-linked gelatin nanoparticles incorporating Yucca schidigera extract as a green co-surfactant for sustained-release drug delivery

Akram Hoshyari1 ,  Reza Ahmadi2 ,  Mojgan Heydari1* ,  Mozhgan Bagheri1 ,  Nader Nezafati1
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1 Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center, Karaj, Alborz, Iran
2 Group Molecular and Industrial Biotechnology, Department of Chemical Engineering, School of Engineering, Polytechnic University of Catalonia, Terrassa, Barcelona, Spain
BMT, 00020 https://doi.org/10.12336/bmt.25.00020
Submitted: 28 April 2025 | Revised: 5 August 2025 | Accepted: 6 August 2025 | Published: 27 August 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Gelatin nanoparticles (GNPs) have been designed and characterized to enable the controlled release of tramadol, offering potential for improved drug delivery and sustained therapeutic effects. In this study, biocompatible GNPs for controlled release of water-soluble drug tramadol were prepared through the water-in-oil emulsion method using Yucca schidigera extract as an eco-friendly, natural green co-surfactant. The presence of an aldimine functional group in the structure of GNPs was confirmed using Fourier-transform infrared spectroscopy, indicating cross-linking of gelatin by glutaraldehyde. In addition, the NPs exhibited a uniform, spherical structure without cracks, and the average particle size increased from 70 to 350 nm as the percentage of the cross-linker agent decreased from 25% to 8% v/v. The ninhydrin test was used to study the degree of cross-linking, and the results showed that 8% and 25% v/v of glutaraldehyde were able to cross-link the gelatin structure. The swelling index of GNPs cross-linked with 25% v/v glutaraldehyde (798%) was lower than with 8% v/v glutaraldehyde (1,030%). The GNP-to-tramadol ratios and glutaraldehyde concentration were optimized for tramadol release, and the results showed that cross-linked gelatin with 25% v/v glutaraldehyde and a GNP-to-tramadol ratio of 1:5 exhibited the most optimal characteristics for controlled drug delivery. Drug release kinetics analysis revealed that the release mechanism is concentration-dependent and best described by a first-order model, indicating a non-Fickian, diffusion-controlled process. Moreover, tramadol released from GNPs showed controlled behavior compared to the commercial tablet. Furthermore, the use of Yucca extract with proven emulsifying and stabilizing properties enhanced NP formation, highlighting its potential as a sustainable alternative to synthetic surfactants. The results confirmed that the designed drug delivery system could be a potential candidate for the delivery and controlled release of drugs such as tramadol compared to available conventional tablets.

Keywords
Gelatin nanoparticles
Water-in-oil emulsion
Yucca schidigera extract
Tramadol hydrochloride
Controlled release
Kinetic models
Funding
This project was financially supported by the Materials and Energy Research Center (MERC, Iran) under the project number 771395064.
Conflict of interest
The authors declare no competing interests.
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