Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
  1. You are here:
  2. Home
  3. Journals
  4. Biological Sciences
RESEARCH ARTICLE   (Open Access)
Contents Vol 3 (1)

Covalently Crosslinked Lipid Nanocapsule-Based Hydrogels Induces the Modern Drug Delivery Efficacy

Saba Niaz 1*, Guillaume Bastiat Partner 2, Patrick Saulnier 2

+ Author Affiliations

Biosensors and Nanotheranostics 3 (1) 1-10 https://doi.org/10.25163/biosensors.319800

Submitted: 05 February 2024 Revised: 03 April 2024  Published: 08 April 2024 

Abstract

Background: The integration of nanotechnology and hydrogel systems offers a promising strategy for localized drug delivery, particularly for hydrophilic and lipophilic drugs with sustained release. Nanoparticle-loaded hydrogels enhance drug pharmacokinetics and biodistribution, opening the door to novel administration routes. However, the potential of these hydrogels has been underutilized due to the reliance on conventional hydrogel architectures. Methods: This study focuses on developing polymer-free lipid nanocapsule (LNC)-based hydrogels using the Michael addition maleimide-thiol reaction to create stable networks. We characterized the viscoelastic properties of these hydrogels by varying LNC concentration, maleimide composition, crosslinker nature, and maleimide/SH molar ratio. Results: Our findings indicate that hydrogel stiffness is significantly influenced by the LNC concentration, maleimide composition, and the nature of the crosslinker. Furthermore, diffusion-based experiments demonstrated that the hydrogel dissolution rate is dependent on the SH PEG crosslinker, while the release behavior of model drugs is influenced by their molecular weight. Conclusion: The study suggests that polymer-free LNC-based hydrogels hold significant potential as drug delivery systems, offering controlled release and reduced toxicity. These findings pave the way for further exploration of novel hydrogel structures in drug administration.

Keywords: Lipid nanocapsules (LNCs), Hydrogels, Covalent crosslinking, Drug delivery systems, Michael addition reaction

References

Bastiancich, C., Bianco, J., Vanvarenberg, K., Ucakar, B., Joudiou, N., Gallez, B., Bastiat, G., Préat, V., & Danhier, F. (2017). Injectable nanomedicine hydrogel for local chemotherapy of glioblastoma after surgical resection. Journal of Controlled Release, 264, 45–54. https://doi.org/10.1016/j.jconrel.2017.08.019

Blanco, E., Shen, H., & Ferrari, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941–951. https://doi.org/10.1038/nbt.3330

Caramella, C.M., Rossi, S., Ferrari, F., Bonferoni, M.C., & Sandri, G. (2015). Mucoadhesive and thermogelling systems for vaginal drug delivery. Advanced Drug Delivery Reviews, 92, 39–52. https://doi.org/10.1016/j.addr.2015.02.001

Cully, M. (2015). Inflammatory diseases: Hydrogel drug delivery for inflammatory bowel disease. Nature Reviews Drug Discovery, 14(10), 678. https://doi.org/10.1038/nrd4744

Duan, Z., Zhu, M., Wang, Y., Xu, L., & Jiang, Y. (2018). The effect of particle size on the cellular uptake and in vivo distribution of nanocarriers. Journal of Nanobiotechnology, 16(1), 129. https://doi.org/10.1186/s12951-018-0477-1

Feng, Q., & Zhao, Y. (2019). The influence of pH and ionic strength on the stability of nanoparticles: The role of environmental conditions. Nanotechnology Reviews, 8(1), 1067–1084. https://doi.org/10.1515/ntrev-2019-0050

Fu, Y., & Kao, W.J. (2011). In situ forming poly(ethylene glycol)-based hydrogels via thiol-maleimide Michael-type addition. Journal of Biomedical Materials Research Part A, 98(2), 201–211. https://doi.org/10.1002/jbm.a.33106

Gazaille, C., Sicot, M., Akiki, M., Lautram, N., Dupont, A., Saulnier, P., Eyer, J., & Bastiat, G. (2021). Characterization of biological material adsorption to the surface of nanoparticles without a prior separation step: A case study of glioblastoma-targeting peptide and lipid nanocapsules. Pharmaceutical Research, 38(5), 681–691. https://doi.org/10.1007/s11095-021-03034-8

Gerwin, N., Hops, C., & Lucke, A. (2006). Intraarticular drug delivery in osteoarthritis. Advanced Drug Delivery Reviews, 58(2), 226–242. https://doi.org/10.1016/j.addr.2006.01.018

Heurtault, B., Saulnier, P., Pech, B., Proust, J.E., & Benoit, J.P. (2002). A novel phase inversion-based process for the preparation of lipid nanocarriers. Pharmaceutical Research, 19(6), 875–880. https://doi.org/10.1023/A:1016121319668

Kang-Mieler, J.J., & Mieler, W.F. (2015). Thermo-responsive hydrogels for ocular drug delivery. Developments in Ophthalmology, 55, 104–111. https://doi.org/10.1159/000434694

Karavasili, C., & Fatouros, D.G. (2016). Smart materials: In situ gel-forming systems for nasal delivery. Drug Discovery Today, 21(1), 157–166. https://doi.org/10.1016/j.drudis.2015.10.016

Karvinen, J., Ihalainen, T.O., Calejo, M.T., Jönkkäri, I., & Kellomäki, M. (2019). Characterization of the microstructure of hydrazone crosslinked polysaccharide-based hydrogels through rheological and diffusion studies. Materials Science and Engineering C, 94, 1056–1066. https://doi.org/10.1016/j.msec.2018.10.048

Lee, J.H., Nam, Y.S., & Lee, K.S. (2017). Thermo-responsive hydrogels for controlled drug release and their applications in cancer therapy. Journal of Biomedical Materials Research Part A, 105(5), 1253–1261. https://doi.org/10.1002/jbm.a.35960

Loren, N., Hagman, J.K., Jonasson, J., Deschout, H., Bernin, D., Cella-Zanacchi, F., Diaspro, A., McNally, J.G., & Ameloot, M. (2015). Fluorescence recovery after photobleaching in material and life sciences: Putting theory into practice. Quarterly Reviews of Biophysics, 48(4), 323–387. https://doi.org/10.1017/S0033583515000013

Lorén, N., Hagman, J.K., Jonasson, J., Deschout, H., Bernin, D., Cella-Zanacchi, F., Diaspro, A., McNally, J.G., & Ameloot, M. (2015). Fluorescence recovery after photobleaching in material and life sciences: Putting theory into practice. Quarterly Reviews of Biophysics, 48(4), 323–387. https://doi.org/10.1017/S0033583515000013

Martinez-Jothar, L., Doulkeridou, S., Schiffelers, R.M., Sastre Torano, S., Oliveira, S., van Nostrum, C.F., & Hennink, W.E. (2018). Insights into maleimide-thiol conjugation chemistry: Conditions for efficient surface functionalization of nanoparticles for receptor targeting. Journal of Controlled Release, 282, 101–109. https://doi.org/10.1016/j.jconrel.2018.03.002

Miller, M.A., & Nelson, D.J. (2020). Biodegradable and bioadhesive hydrogels for controlled release of bioactive compounds. Journal of Controlled Release, 328, 329–343. https://doi.org/10.1016/j.jconrel.2020.09.029

Perrier, T., Saulnier, P., Fouchet, F., Lautram, N., & Benoît, J.P. (2010). Post-insertion into Lipid NanoCapsules (LNCs): From experimental aspects to mechanisms. International Journal of Pharmaceutics, 396(1–2), 204–209. https://doi.org/10.1016/j.ijpharm.2010.06.019

Petros, R.A., & Desimone, J.M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 9(8), 615–627. https://doi.org/10.1038/nrd2591

Pitorre, M., Gazaille, C., Pham, L.T.T., Frankova, K., Béjaud, J., Lautram, N., Riou, J., Perrot, R., Geneviève, F., & Moal, V. (2021). Polymer-free hydrogel made of lipid nanocapsules, as a local drug delivery platform. Materials Science and Engineering C, 126, 112188. https://doi.org/10.1016/j.msec.2021.112188

Rupp, R., Rosenthal, S.L., & Stanberry, L.R. (2007). VivaGel™ (SPL7013 Gel): A candidate dendrimer-microbicide for the prevention of HIV and HSV infection. International Journal of Nanomedicine, 2(4), 561–566. https://doi.org/10.2147/IJN.S1232

Shen, M., Xu, Y.Y., Sun, Y., Duan, Y.R., & Han, B.S. (2015). Preparation of a thermosensitive gel composed of a mPEG-PLGA-PLL-cRGD nanodrug delivery system for pancreatic tumor therapy. ACS Applied Materials & Interfaces, 7(35), 20530–20537. https://doi.org/10.1021/acsami.5b06043

Shi, J., Farokhzad, O.C., Votruba, A.R., & Langer, R. (2010). Nanotechnology in drug delivery and tissue engineering: From discovery to applications. Nano Letters, 10(10), 3223–3230. https://doi.org/10.1021/nl102184c

Shi, J., Kantoff, P.W., Wooster, R., & Farokhzad, O.C. (2017). Cancer nanomedicine: Progress, challenges and opportunities. Nature Reviews Cancer, 17(1), 20–37. https://doi.org/10.1038/nrc.2016.108

Summonte, S., Racaniello, G.F., Lopedota, A., Denora, N., & Bernkop-Schnürch, A. (2021). Thiolated polymeric hydrogels for biomedical application: Cross-linking mechanisms. Journal of Controlled Release, 330, 470–482. https://doi.org/10.1016/j.jconrel.2020.12.037

Wong, R.S.H., Ashton, M., & Dodou, K. (2015). Effect of crosslinking agent concentration on the properties of unmedicated hydrogels. Pharmaceutics, 7(3), 305–319. https://doi.org/10.3390/pharmaceutics7030305

Wu, Z.X., Zou, X.Y., Yang, L.L., Lin, S., Fan, J., Yang, B., Sun, X.Y., Wan, Q., Chen, Y., & Fu, S.Z. (2014). Thermosensitive hydrogel used in dual drug delivery system with paclitaxel-loaded micelles for in situ treatment of lung cancer. Colloids and Surfaces B: Biointerfaces, 122, 90–98. https://doi.org/10.1016/j.colsurfb.2014.06.052

Zhou, Y., Li, Z., Zhang, Y., & Wang, H. (2021). A review of drug delivery systems for hydrophobic drugs: Nanocarriers and their applications. Journal of Nanobiotechnology, 19(1), 160. https://doi.org/10.1186/s12951-021-01092-8

PDF
Abstract
Export Citation

View Dimensions


View Plumx


View Altmetric




Save
0
Citation
268
View

Share