Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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RESEARCH ARTICLE   (Open Access)
Contents Vol 2 (1)

pH-Responsive Nanogels for Site-Specific Drug Delivery: Synthesis, Characterization, and Stimuli-Triggered Release Behavior

Saba Niaz 1, Sam Au 1*

+ Author Affiliations

Biosensors and Nanotheranostics 2 (1) 1-10 https://doi.org/10.25163/biosensors.219916

Submitted: 19 September 2023 Revised: 18 November 2023  Published: 20 November 2023 

Abstract

Background: Traditional drug delivery systems face limitations such as low solubility, instability, and toxicity, which can impact efficacy and safety. pH-responsive nanogels offer an innovative approach for controlled and targeted drug delivery, particularly for oral administration, by releasing drugs based on environmental pH changes. Objective: This study aimed to synthesize and characterize novel, physically cross-linked pH-responsive nanogels using poly(L-lysine isophthalamide) grafted with decylamine (PLP-NDA) and evaluate their potential as oral drug delivery vehicles. Methods: PLP-NDA nanogels were synthesized using a surfactant-free nanoprecipitation method, combining anionic and amphiphilic properties with hydrophobic segments for stable nanogel formation and drug loading. The nanogels were characterized for particle size, zeta potential, and stability under varied ionic strengths and pH levels. Nile red (NR) was used as a model hydrophobic drug to assess encapsulation efficiency and release profiles in simulated fasted gastric (pH 1.6) and intestinal fluids (pH 6.5). Results: The synthesized PLP-NDA nanogels had an average particle size of 101.3 ± 1.2 nm and a zeta potential of -37.51 ± 3.32 mV, demonstrating stability over 28 days. Encapsulation efficiency of NR was 16.5 ± 2.1%, with a particle size of 124.5 ± 2.1 nm for PLP-NDA-NR nanogels. Drug release studies showed complete release in intestinal fluid (pH 6.5) within 24 hours, while release in gastric fluid (pH 1.6) was 54.0 ± 3.7%. Conclusion: PLP-NDA nanogels exhibit favorable characteristics for pH-triggered drug release, showing stability and efficient drug encapsulation. These nanogels are promising candidates for oral drug delivery systems targeting gastrointestinal applications, with potential for future clinical development.

Keywords: pH-responsive nanogels, Drug delivery systems (DDS), Polymeric hydrogels, Site-specific release, Biocompatible nanocarriers

References

Ahmed, E. M. (2015). Hydrogel: Preparation, characterization, and applications: A review. Journal of Advanced Research, 6(2), 105–121. https://doi.org/10.1016/j.jare.2013.07.006

Akiyama, H., Endo, T., Matsuda, H., & Katsumata, Y. (2007). Size effect of nanoparticles on the formation of complex coacervates. Journal of Colloid and Interface Science, 315(2), 390–397. https://doi.org/10.1016/j.jcis.2007.07.016

Arifin, D. R., & Lee, S. Y. (2021). Recent advancements in pH-responsive nanogel carriers for targeted drug delivery. Materials Science and Engineering: C, 126, 112335. https://doi.org/10.1016/j.msec.2021.112335

Bagalkot, V., Farokhzad, O. C., & Jon, S. (2006). Nanoparticles for drug delivery: pH-responsive carriers. Advanced Drug Delivery Reviews, 58(9), 1333-1344. https://doi.org/10.1016/j.addr.2006.09.002

Bhattacharya, S., & Kundu, S. C. (2020). pH-sensitive hydrogels and nanogels for drug delivery applications. Journal of Controlled Release, 322, 323-341. https://doi.org/10.1016/j.jconrel.2020.03.019

Chen, Y., Zhang, X., Li, Y., & Xie, S. (2017). Synthesis and characterization of poly(L-lysine isophthalamide) nanogels with functionalized amine groups for drug delivery. Journal of Nanoscience and Nanotechnology, 17(1), 324-330. https://doi.org/10.1166/jnn.2017.1358

Gao, Y., & Wu, C. (2021). Fabrication and application of pH-responsive nanocarriers for controlled drug delivery. Journal of Biomedical Nanotechnology, 17(5), 875-891. https://doi.org/10.1166/jbn.2021.3162

Gao, Y., Sun, X., Shen, J., Yu, S., Sun, C., & Xu, L. (2013). The potential of pH-sensitive nanogels in drug delivery. Colloids and Surfaces B: Biointerfaces, 103, 244–249. https://doi.org/10.1016/j.colsurfb.2012.10.042

Gu, X., Zhang, H., Xu, J., & Wu, W. (2013). Advances in drug delivery using nanogel systems: A review. European Journal of Pharmaceutical Sciences, 50(1), 1-11. https://doi.org/10.1016/j.ejps.2013.01.018

Jia, Y., Zhang, Y., Liu, X., & Wang, H. (2017). Theoretical and experimental study of the Schiff base formation between amines and aldehydes. Journal of Organic Chemistry, 82(16), 7321-7327. https://doi.org/10.1021/acs.joc.7b00722

Karimi, M., Ghasemi, A., Sahandi Zangabad, P., Rahighi, R., Basri, S. M. M., Mirshekari, H., ... & Hamblin, M. R. (2016b). Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chemical Society Reviews, 45(5), 1457–1501. https://doi.org/10.1039/C5CS00798D

Kepinska, M., Hwang, D., Youn, J., & Kim, J. (2013). Structural and photophysical properties of Nile red: Implications for its use in cellular imaging. Biochemistry, 52(6), 1007-1016. https://doi.org/10.1021/bi301385f

Kim, H., & Kim, Y. (2021). Advances in the synthesis and application of pH-responsive nanogels for drug delivery. Polymers, 13(22), 3896. https://doi.org/10.3390/polym13223896

Koetting, M. C., Peters, J. T., Steichen, S. D., & Peppas, N. A. (2015). Stimulus-responsive hydrogels: Theory, modern advances, and applications. Materials Science and Engineering: R: Reports, 93, 1–49. https://doi.org/10.1016/j.mser.2015.04.001

Kurniasih, T., Hasan, N., & Andayani, W. (2015). Impact of local environment on the fluorescence intensity of Nile red: Application to drug delivery systems. Journal of Fluorescence, 25(5), 1205-1214. https://doi.org/10.1007/s10895-015-1617-8

Li, Z., Yang, X., & Liu, Y. (2019). The role of pH-responsive nanocarriers in cancer therapy: A review. Nanomedicine: Nanotechnology, Biology, and Medicine, 17(1), 29-49. https://doi.org/10.1016/j.nano.2019.04.014

Lockhart, T. J., Gole, A., & Alivisatos, A. P. (2016). Nanogel synthesis and characterization using dynamic light scattering. Nanotechnology Reviews, 5(2), 143-152. https://doi.org/10.1515/ntrev-2016-0007

Neamtu, I., Rusu, A. G., Diaconu, A., Nita, L. E., Chiriac, A. P., & Popa, M. (2017). Nanogels designed for drug delivery and biomedical applications. Drug Delivery, 24(1), 539–557. https://doi.org/10.1080/10717544.2017.1291054

Raemdonck, K., Demeester, J., & De Smedt, S. C. (2009). Advanced nanogel engineering for drug delivery. Advanced Drug Delivery Reviews, 61(4), 414–426. https://doi.org/10.1016/j.addr.2009.03.008

Sam Au (2023). "Transitioning Layer-by-Layer Nanocapsule Synthesis from Batch to Continuous Production: Optimizing Calcium Phosphate Core Template Encapsulation", Biosensors and Nanotheranostics, 2(1),1-7, 9912.

Sasaki, Y., & Akiyoshi, K. (2010). Nanogel engineering for new nanobiomaterials: Chemical modification of nanogels and their biomedical applications. Chemical Record, 10(6), 366–376. https://doi.org/10.1002/tcr.201000011

Schoener, C. A., & Peppas, N. A. (2012). Molecular imprinted hydrogels in drug delivery. Advanced Drug Delivery Reviews, 64(11), 1505–1520. https://doi.org/10.1016/j.addr.2012.07.010

Soni, S., & Yadav, K. S. (2016). Nanogels as potential nanomedicine carriers for cancer therapy. Drug Delivery, 23(1), 231–246. https://doi.org/10.3109/10717544.2014.928727

Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R., & Rudzinski, W. E. (2002). Biodegradable polymeric nanoparticles as drug delivery devices. Journal of Controlled Release, 70(1-2), 1–20. https://doi.org/10.1016/S0168-3659(00)00339-4

Vashist, A., Ahmad, S., Dev, A., Gupta, Y. K., & Maiti, P. (2014). Stimuli-responsive hydrogels for therapeutics. Advances in Drug Delivery Systems, 45(4), 1637–1656. https://doi.org/10.1016/j.addr.2013.10.007

Wu, Y., & Wang, Z. (2016). Nanogels for advanced drug delivery. Advanced Drug Delivery Reviews, 107, 2–14. https://doi.org/10.1016/j.addr.2016.05.010

Zhang, S., Shubin, Z., Chen, Y., & Li, W. (2016). Optimization of drug loading in nanogel systems: Effects of polymer concentration and drug properties. International Journal of Pharmaceutics, 514(1), 65-72. https://doi.org/10.1016/j.ijpharm.2016.09.038

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