Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model

Autor: Seokmann Hong, Hyo Kyung Han, So Youn Ro, Hyun Woo Ma, Jae Hee Cheon, I Seul Park, Jung Min Kim, Da Hye Kim, Hyo Jeong Park, Soo Jeong Lim, Seung Won Kim, Mi Jeong Son
Jazyk: angličtina
Rok vydání: 2020
Předmět:
medicine.medical_treatment
Pharmaceutical Science
Medicine (miscellaneous)
Administration
Oral
02 engineering and technology
Pharmacology
Applied Microbiology and Biotechnology
Inflammatory bowel disease
Nanocomposites
Mice
Drug Delivery Systems
Oral delivery system
Lymphocytes
0303 health sciences
biology
Antibodies
Monoclonal
021001 nanoscience & nanotechnology
Colitis
Cytokine
lcsh:R855-855.5
Systemic administration
Molecular Medicine
Cytokines
Tumor necrosis factor alpha
Antibody
0210 nano-technology
medicine.drug
lcsh:Medical technology
medicine.drug_class
Colon
lcsh:Biotechnology
Biomedical Engineering
Bioengineering
Monoclonal antibody
03 medical and health sciences
lcsh:TP248.13-248.65
medicine
Animals
Humans
Particle Size
030304 developmental biology
business.industry
Tumor Necrosis Factor-alpha
Research
medicine.disease
Inflammatory Bowel Diseases
Infliximab
Mice
Inbred C57BL
Disease Models
Animal
Nanocomposite carrier
Liposomes
biology.protein
Leukocytes
Mononuclear
business
Zdroj: Journal of Nanobiotechnology, Vol 18, Iss 1, Pp 1-13 (2020)
Journal of Nanobiotechnology
ISSN: 1477-3155
DOI: 10.1186/s12951-020-00693-4
Popis: Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration. We developed a colon-specific drug delivery system for the oral administration of IFX using ternary nanocomposite carriers. Nanocomposite carriers consisting of liposomes, aminoclay-coated liposomes (AC-L), Eudragit S100 AC-L (EAC-L) or those carrying IFX (IFX-L, AC-IFX-L, and EAC-IFX-L) were orally administered to mice with dextran sulfate sodium-induced colitis. We evaluated the effects of nanocomposite carriers on lymphocytes and monocytes in peripheral blood mononuclear cells (PBMC) of IBD patients. We studied the therapeutic effects of the nanocomposites themselves and nanocomposites with IFX at target sites in vivo and in vitro . All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions ( Tnfa , Il1b , and Il17 ). We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.
Databáze: OpenAIRE
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