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Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes Decorated with a Sialic Acid Conjugate for Rheumatoid Arthritis Treatment.
- Source :
-
Pharmaceutical research [Pharm Res] 2019 May 10; Vol. 36 (7), pp. 97. Date of Electronic Publication: 2019 May 10. - Publication Year :
- 2019
-
Abstract
- Purpose: The aim of this research was to design dexamethasone palmitate (DP) loaded sialic acid modified liposomes, with the eventual goal of using peripheral blood neutrophils (PBNs) that carried drug-loaded liposomes to improve the therapeutic capacity for rheumatoid arthritis (RA).<br />Methods: A sialic acid - cholesterol conjugate (SA-CH) was synthesized and anchored on the surface of liposomal dexamethasone palmitate (DP-SAL). The physicochemical characteristics and in vitro cytotoxicity of liposomes were evaluated. Flow cytometry and confocal laser scanning microscopy were utilized to investigate the accumulation of liposomes in PBNs. The adjuvant-induced arthritis was adopted to investigate the targeting ability and anti-inflammatory effect of DP loaded liposomes.<br />Results: Both DP-CL and DP-SAL existed an average size less than 200 nm with remarkably high encapsulation efficiencies more than 90%. In vitro and in vivo experiments manifested SA-modified liposomes provided a reinforced accumulation of DP in PBNs. As well, DP-SAL displayed a greater degree of accumulation in the joints and a stronger anti-inflammatory effect in terms of RA suppression.<br />Conclusions: SA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.
- Subjects :
- Animals
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents pharmacokinetics
Anti-Inflammatory Agents toxicity
Arthritis, Experimental drug therapy
Arthritis, Experimental pathology
Arthritis, Rheumatoid pathology
Cholesterol chemistry
Dexamethasone administration & dosage
Dexamethasone toxicity
Drug Liberation
Joints drug effects
Joints pathology
L-Selectin metabolism
Macrophages, Peritoneal drug effects
Macrophages, Peritoneal pathology
Male
Neutrophils pathology
Palmitates chemistry
Rats, Wistar
Tissue Distribution
Arthritis, Rheumatoid drug therapy
Dexamethasone pharmacokinetics
Liposomes chemistry
N-Acetylneuraminic Acid chemistry
Neutrophils metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-904X
- Volume :
- 36
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 31076925
- Full Text :
- https://doi.org/10.1007/s11095-019-2609-4