Oral administration of chondroitin sulfate-functionalized nanoparticles for colonic macrophage-targeted drug delivery

Xueqing Zhang; Ya Ma; Lijun Ma; Menghang Zu; Heliang Song; Bo Xiao

doi:10.1016/j.carbpol.2019.115126

Oral administration of chondroitin sulfate-functionalized nanoparticles for colonic macrophage-targeted drug delivery

Carbohydr Polym. 2019 Nov 1:223:115126. doi: 10.1016/j.carbpol.2019.115126. Epub 2019 Jul 26.

Authors

Xueqing Zhang¹, Ya Ma¹, Lijun Ma², Menghang Zu³, Heliang Song⁴, Bo Xiao⁵

Affiliations

¹ State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Beibei, Chongqing, 400715, PR China; Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, Beibei, Chongqing, 400715, PR China.
² Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, Beibei, Chongqing, 400715, PR China.
³ Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Materials and Energy, Southwest University, Beibei, Chongqing, 400715, PR China; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Beibei, Chongqing, 400715, PR China.
⁴ Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA.
⁵ State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Beibei, Chongqing, 400715, PR China; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Beibei, Chongqing, 400715, PR China; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA. Electronic address: bxiao@swu.edu.cn.

PMID: 31426992
DOI: 10.1016/j.carbpol.2019.115126

Abstract

Orally targeted delivery of anti-inflammatory drugs to macrophages has attracted great attention for minimizing the symptoms of ulcerative colitis (UC). In this investigation, we encapsulated curcumin (CUR) into polymeric nanoparticles (NPs), and conjugated chondroitin sulfate (CS) to their surfaces. The resulting CS-NPs had an average diameter of 281 nm, monodisperse size distribution and negatively charged surface. Cell experiments indicated that these NPs showed excellent biocompatibility, and yielded significantly higher cell internalization efficiency in Raw 264.7 macrophages than their counterparts (carboxymethyl cellulose-functionalized CUR-encapsulated NPs, CUL-NPs). Moreover, CS-NPs exhibited a dramatically stronger capacity to inhibit the secretion of the major pro-inflammatory cytokines from lipopolysaccharide-stimulated macrophages compared with CUL-NPs. In vivo experiments revealed that oral administration of chitosan/alginate hydrogel embedding CS-NPs achieved better therapeutic outcomes against UC comparied with CUL-NPs. Collectively, our results demonstrated that CS-NP-embedded hydrogel held a great promise to be developed as a macrophage-targeted drug delivery system for UC treatment.

Keywords: Chondroitin sulfate; Macrophage-targeted drug delivery; Nanotherapeutic; Oral administration; Ulcerative colitis.

MeSH terms

Administration, Oral
Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Chondroitin Sulfates / administration & dosage
Chondroitin Sulfates / chemistry*
Chondroitin Sulfates / pharmacology
Colitis, Ulcerative / drug therapy*
Colitis, Ulcerative / metabolism
Colon / drug effects*
Colon / metabolism
Curcumin / administration & dosage
Curcumin / pharmacology*
Cytokines / antagonists & inhibitors
Cytokines / metabolism
Drug Delivery Systems*
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Macrophages / drug effects*
Macrophages / metabolism
Mice
Nanoparticles / administration & dosage
Nanoparticles / chemistry*
Particle Size
RAW 264.7 Cells
Surface Properties

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cytokines
Lipopolysaccharides
Chondroitin Sulfates
Curcumin