Abstract | BACKGROUND: METHODS: CSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs. RESULTS: PNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum-colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs. CONCLUSION: Overall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.
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Authors | Muhammad Naeem, Junhwan Bae, Murtada A Oshi, Min-Soo Kim, Hyung Ryong Moon, Bok Luel Lee, Eunok Im, Yunjin Jung, Jin-Wook Yoo |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 13
Pg. 1225-1240
( 2018)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 29535519
(Publication Type: Journal Article)
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Chemical References |
- Cytokines
- Drug Carriers
- Immunosuppressive Agents
- Inflammation Mediators
- Methylmethacrylates
- Polylactic Acid-Polyglycolic Acid Copolymer
- Polyglycolic Acid
- Lactic Acid
- Cyclosporine
- Peroxidase
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Topics |
- Administration, Oral
- Animals
- Body Weight
- Colitis
(chemically induced, drug therapy, pathology)
- Colon
(pathology)
- Cyclosporine
(administration & dosage, therapeutic use)
- Cytokines
(metabolism)
- Drug Carriers
(administration & dosage)
- Drug Delivery Systems
- Drug Liberation
- Hydrogen-Ion Concentration
- Immunosuppressive Agents
(therapeutic use)
- Inflammation Mediators
(metabolism)
- Lactic Acid
(chemistry)
- Macrophages
(drug effects, pathology)
- Methylmethacrylates
(chemistry)
- Mice, Inbred ICR
- Nanoparticles
(administration & dosage, chemistry, ultrastructure)
- Particle Size
- Peroxidase
(metabolism)
- Polyglycolic Acid
(chemistry)
- Polylactic Acid-Polyglycolic Acid Copolymer
- Treatment Outcome
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