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. 2023 Jan 20;28(3):1040.
doi: 10.3390/molecules28031040.

A Celastrol Drug Delivery System Based on PEG Derivatives: The Structural Effects of Nanocarriers

Yansong Zhang  1 , Lijuan Ding  2 , Ting Wang  2 , Xiangtao Wang  2 , Bo Yu  2 , Fei Jia  2 , Meihua Han  2 , Yifei Guo  2   3   4
Affiliations

A Celastrol Drug Delivery System Based on PEG Derivatives: The Structural Effects of Nanocarriers

Yansong Zhang et al. Molecules. .

Abstract

The therapeutic efficacy of nanoscale drug delivery systems is related to particle size, zeta potential, morphology, and other physicochemical properties. The structure and composition of nanocarriers may affect their physicochemical properties. To systematically evaluate these characteristics, three analogues, namely polyethylene glycol (PEG), PEG-conjugated octadecylamine (PEG-C18), and tri(ethylene glycol) (TEG), were explored as nanocarriers to entrap celastrol (CSL) via the injection-combined dialysis method. CSL nanoparticles were successfully prepared as orange milky solutions, which revealed a similar particle size of approximately 120 nm, with narrow distribution and a negative zeta potential of -20 mV. All these CSL nanoparticles exhibited good storage stability and media stability but presented different drug-loading capacities (DLCs), release profiles, cytotoxicity, and hemolytic activity. For DLCs, PEG-C18/CSL exhibited better CSL entrapment capacity. Regarding the release profiles, TEG/CSL showed the lowest release rate, PEG-C18/CSL presented a moderate release rate, and PEG/CSL exhibited a relatively fast release rate. Based on the different release rates, PEG-C18/CSL and TEG/CSL showed higher degrees of cytotoxicity than PEG/CSL. Furthermore, TEG/CSL showed the lowest membrane toxicity, and its hemolytic rate was below 20%. These results suggest that the structural effects of nanocarriers can affect the interactions between nanocarriers and drugs, resulting in different release profiles and antitumor activity.

Keywords: composition; degree of branching; hydrophobic interaction; steric hindrance; structural effect.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of three nanocarriers and illustration of CSL-loaded nanoparticles.
Figure 2
Figure 2
Particle size distribution curves of PEG/CSL (a), PEG-C18/CSL (c), TEG/CSL (e), and TEM images of PEG/CSL (b), PEG-C18/CSL (d), and TEG/CSL (f). Scale bar: 100 nm.
Figure 3
Figure 3
Particle size of three CSL nanoparticles during the entire storage process (n = 3).
Figure 4
Figure 4
Particle sizes of CSL nanoparticles in 5% glucose solution (a) and plasma (b) after 24 h of incubation, n = 3.
Figure 5
Figure 5
Cumulative release rates of CSL DMSO solution and CSL nanoparticles at 37 °C, n = 3.
Figure 6
Figure 6
Inhibition rates of free CSL and CSL nanoparticles in 4T1 cell line at 37 °C after 48 h incubation, n = 5.
Figure 7
Figure 7
Hemolytic rate of CSL nanoparticles in normal red blood cells at 37 °C after 4 h incubation, n = 5.
See this image and copyright information in PMC

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References

    1. Wang J., Ni Q., Wang Y., Zhang Y., He H., Gao D., Ma X., Liang X.-J. Nanoscale drug delivery systems for controllable drug behaviors by multi-stage barrier penetration. J. Control. Release. 2021;331:282–295. doi: 10.1016/j.jconrel.2020.08.045. - DOI - PubMed
    1. Moghassemi S., Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: An illustrated review. J. Control. Release. 2014;185:22–36. doi: 10.1016/j.jconrel.2014.04.015. - DOI - PubMed
    1. Wang X., Li C., Wang Y., Chen H., Zhang X., Luo C., Zhou W., Li L., Teng L., Yu H., et al. Smart drug delivery systems for precise cancer therapy. Acta Pharm. Sin. B. 2022;12:4098–4121. doi: 10.1016/j.apsb.2022.08.013. - DOI - PMC - PubMed
    1. Guo X., Wang L., Duval K., Fan J., Zhou S., Chen Z. Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-Traceable Drug Release. Adv. Mater. 2018;30:1705436. doi: 10.1002/adma.201705436. - DOI - PMC - PubMed
    1. Förster S., Antonietti M. Amphiphilic Block Copolymers in Structure-Controlled Nanomaterial Hybrids. Adv. Mater. 1998;10:195–217. doi: 10.1002/(SICI)1521-4095(199802)10:3<195::AID-ADMA195>3.0.CO;2-V. - DOI