Development of pH-Responsive smart hydrogel incorporating basil eugenol and anthocyanin for controlled drug delivery
Keywords:
Smart hydrogel, chitosan–acrylic acid, eugenol, controlled drug release, anthocyanin sensorAbstract
This study aimed to develop a pH-responsive smart hydrogel system based on chitosan–acrylic acid, fortified with butterfly pea (Clitoria ternatea) extract as a visual stability sensor and loaded with basil (Ocimum basilicum) leaf derived eugenol as a natural antidepressant. The hydrogel was synthesized through free-radical polymerization and characterized in terms of drug loading, release behavior, and structural interactions. Drug release tests under simulated physiological conditions revealed minimal eugenol release at pH 6.8 (oral cavity), limited release at pH 1.2 (gastric environment), and maximal release at pH 7.4 (intestinal environment). The formulation containing 2.6% acrylic acid demonstrated optimal performance, achieving high release levels in the intestine without premature loss. FTIR analysis confirmed successful grafting of acrylic acid, the incorporation of eugenol and anthocyanins, and the presence of new intermolecular interactions that enhanced structural stability. These findings indicate that the developed hydrogel holds significant potential as a controlled drug delivery system, combining therapeutic efficacy with an integrated colorimetric monitoring function.
References
Aburel, O. M., Pavel, I. Z., Dănilă, M. D., Lelcu, T., Roi, A., Lighezan, R., Muntean, D. M., dan Rusu,
L. C. 2021. Pleiotropic effects of eugenol: the good, the bad, and the unknown. Oxidative
Medicine and Cellular Longevity. 20(19):1-15.
Ahmad, N. A., Heng, Y. L., Salam, F., Zaid, M. M. H., dan Hanifah, A. S. 2019. A colorimetric pH
sensor based on Clitoria sp and Brassica sp for monitoring of food spoilage using chromametry.
Sensors. 19(21):1-19.
Ali, A., dan Ahmed, S. 2024. Polysaccharides-Based Hydrogels. Edisi ke-1, Elsevier. India.
Chen, X., Low, H. R., Loi, X. Y., et al. (2019). Fabrication and evaluation of bacterial
nanocellulose/poly(acrylic acid)/graphene oxide composite hydrogel: Characterizations and
biocompatibility studies for wound dressing. Journal of Biomedical Materials Research Part B:
Applied Biomaterials, 110(2), 2140–2151. https://doi.org/10.1002/jbm.b.34309
Ghosh, S., Kumar, N., dan Chattopadhyay, S. 2024. Electrically conductive “smart” hydrogels for ondemand
drug delivery. Asian Journal of Pharmaceutical Sciences. 20(1):1-22.
Global Burden of Disease Study. 2024. Global Burden of Disease Report 2024. Institute for Health
Metrics from https://www.healthdata.org/gbd. Diakses tanggal 10 Mei 2025.
Handayani, L., Aprilia, S., Arahman, N., dan Bilad, R. M. 2024. Identification of the anthocyanin
profile from butterfly pea (Clitoria ternatea L.) flowers under varying extraction conditions
evaluating its potential as a natural blue food colorant and its application as a colorimetric
indicator. South African Journal of Chemical Engineering. 49:151-161.
Hong, F., Qiu, P., Wang, Y., Ren, P., Liu, J., Zhao, J., & Guo, D. (2024). Chitosan-based hydrogels:
From preparation to applications—A review. Food Chemistry: X, 21, 101094.
https://doi.org/10.1016/j.fochx.2023.101095
Ijaz, H., Tulain, U. R., Minhas, M. U., et al. (2022). Design and in vitro evaluation of pH-sensitive
crosslinked chitosan-grafted acrylic acid copolymer (CS-co-AA) for targeted drug delivery.
International Journal of Polymeric Materials and Polymeric Biomaterials, 71(6), 336–348.
https://doi.org/10.1080/00914037.2020.1833011
Kopač, T., Ručigaj, A., dan Krajnc, M. 2020. The mutual effect of the crosslinker and biopolymer
concentration on the desired hydrogel properties. International Journal of Biological
Macromolecules. 159:557–569.
Koshy, R. R., Reghunadhan, A. Mary, K. S., Pillai, S. P., Joseph, S., dan Pothen, A. L. 2022. pH
indicator films fabricated from soy protein isolate modified with chitin nanowhisker and
Clitoria ternatea flower extract. Current Research in Food Science. 5:743-751.
Liaqat, H., Khalid, A., Riaz, T., et al. (2024). pH-Sensitive hydrogels fabricated with hyaluronic acid
as a matrix for targeted mesalamine release. ACS Omega, 9(38), 22083–22095.
https://doi.org/10.1021/acsomega.4c03240
Malik, N. S., Ahmad, M., Alqahtani, M. S., et al. (2021). β-cyclodextrin chitosan-based hydrogels
with tunable pH-responsive properties for controlled release of acyclovir: Design,
characterization, safety, and pharmacokinetic evaluation. Drug Delivery, 28(1), 1093–1108.
https://doi.org/10.1080/10717544.2021.1921074
Noureen, S., Noreen, S., Ghumman, S. A., et al. (2023). A novel pH-responsive hydrogel system
based on Prunus armeniaca gum and acrylic acid: Preparation and evaluation as a potential
candidate for controlled drug delivery. European Journal of Pharmaceutical Sciences, 189,
https://doi.org/10.1016/j.ejps.2023.106555
Pelin, I. M., Stancu, I.-C., Dinescu, S., & Costache, M. (2023). Tri-component hydrogel as template
for nanocrystalline hydroxyapatite. Gels, 9(11), 884. https://doi.org/10.3390/gels9110905
Rahma, S.P. dan Suzana, D. 2024. Antidepressant activity test of basil leaf essential oil (Ocimum
basilicum L.) with open field test (OFT) method. Jurnal Farmasi dan Farmakoinformatika.
(1):9–22.
Sahoo, D. R., dan Biswal, T. 2024. A comparative study of the drug delivery behaviour of poly
acrylic acid (PAA) reinforced with chitosan, guargum and pectin. Materials Today:
Proceedings. 11(1):1-14.
Salahuddin, A., Ashraf, A., Ahmad, K., dan Hou, H. 2024. Recent advances in chitosan-based smart
hydrogel for drug delivery systems. International Journal of Biological Macromolecules.
(1):135803.
Silva, E. R., Teixeira, L. J. Q., Ribeiro, J. A., Oliveira, R. L., & Oliveira, F. C. (2021). The
performance evaluation of Eugenol and Linalool microencapsulated by PLA on their activities
against pathogenic bacteria. Materials Today Chemistry, 21, 100517.
https://doi.org/10.1016/j.mtchem.2021.100493
Suhail, M., Liu, J. Y., Hsieh, W. C., et al. (2022). Designing of pH-responsive ketorolac
tromethamine loaded hydrogels of alginic acid: Characterization, in-vitro and in-vivo evaluation.
Arabian Journal of Chemistry, 15(5), 103590. https://doiorg.
proxy.undip.ac.id/10.1016/j.arabjc.2021.103590
Suryani, P. R., Zulissetiana, E. F., dan Prananjaya, B. A. 2019. Antidepressant activity of basil leaves
essential oil (Ocimum basilicum) in male balb/c mice. Sriwijaya International Conference on
Medical and Sciences. 26-27, Oktober 2018, Sumatra Selatan, Indonesia. 1246(012065):1-8.
Suttiarporn, P., Taithaisong, T., Namkhot, S., & Luangkamin, S. (2025). Enhanced eugenol
composition in clove essential oil by deep eutectic solvent–based ultrasonic extraction and
microwave-assisted hydrodistillation. Molecules, 30(3), 504.
https://doi.org/10.3390/molecules30030504
Thang, N. H., Chien, T. B., dan Cuong, D. X. 2023. Polymer-based hydrogels applied in drug delivery:
an overview. Gels. 9(523): 1-38.
Tripathy, N. S., Sahoo, L., Paikray, S. K., dan Dilnawaz, F. 2024. Eugenol: The phytocompound's
potential biological applications. BioNanoScience. 14:4044–4055.
Uddin, M. S., Mahin, M. R., Rumi, M. H., & Haque, M. S. (2024). Effect of crosslinking agents on
chitosan hydrogel: A review. Gels, 10(7), 421. https://doi.org/10.3390/gels10070421
Wang, Y., Wang, J., Yuan, Z., Han, H., Li, T., Li, L., dan Guo, X. 2017. Chitosan cross linked
poly(acrylic acid) hydrogels: drug release control and mechanism. Colloids and Surfaces B:
Biointerfaces. 152: 252-259.
Yadav, P., Singh, S., Jaiswal, S., dan Kumar, R. 2024. Synthetic and natural polymer hydrogels: a
review of 3D spheroids and drug delivery. International Journal of Biological Macromolecules.
(4):136126.
Zhu, H., Sun, H., Dai, J., Hao, J., dan Zhou, B. 2024. Chitosan-based hydrogels in cancer therapy:
drug and gene delivery, stimuli-responsive carriers, phototherapy and immunotherapy.
International Journal of Biological Macromolecules. 282(2):137047.
