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Sialic Acid Conjugate–Modified Liposomal Dexamethasone Palmitate Targeting Neutrophils for Rheumatoid Arthritis Therapy: Influence of Particle Size

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Abstract

Many anti-inflammatory therapies targeting neutrophils have been developed so far. A sialic acid (SA)–modified liposomal (SAL) formulation, based on the high expression of L-selectin in peripheral blood neutrophils (PBNs) and SA as its targeting ligand, has proved to be an effective neutrophil-mediated drug delivery system targeting rheumatoid arthritis (RA). The objective of this study was to investigate the influence of particle size of drug-carrying SALs transported and delivered by neutrophils on their anti-RA effect. Dexamethasone palmitate–loaded SALs (DP-SALs) of different particle sizes (300.2 ± 5.5 nm, 150.3 ± 4.3 nm, and 75.0 ± 3.9 nm) were prepared with DP as a model drug. Our study indicated that DP-SALs could efficiently target PBNs, with larger liposomes leading to higher drug accumulation in cells. However, a high intake of large DP-SALs by PBNs inhibited their migration ability and capacity to release the payload at the target site. In contrast, small DP-SALs (75.0 ± 3.9 nm) could maintain the drug delivery potential of PBNs, leading to their efficient accumulation at the inflammatory site, where PBNs would be excessively activated to form neutrophil extracellular traps along with efficient payload release (small DP-SALs) and finally to induce excellent anti-RA effect.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Number. 81973271 and 81703456) and Disruptive Technology Innovation Guidance Fund of Shenyang Pharmaceutical University (Grant Number. 51120666).

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  1. Shuo Wang and Shuaishuai Yang contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China

    Shuo Wang, Xiaoxue Lai, Yanzhi Song, Ling Hu, Cong Li, Xinrong Liu & Yihui Deng

  2. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, China

    Shuaishuai Yang, Tao Shi & Guoliang Chen

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  1. Shuo Wang
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Wang, S., Yang, S., Lai, X. et al. Sialic Acid Conjugate–Modified Liposomal Dexamethasone Palmitate Targeting Neutrophils for Rheumatoid Arthritis Therapy: Influence of Particle Size. AAPS PharmSciTech 22, 16 (2021). https://doi.org/10.1208/s12249-020-01870-2

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