Designing lipid nanostructures for local delivery of biologically active macromolecules

J.M. Brewer, M. Trif, A. Roseanu, J.H. Brock

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

This study focuses on the possible therapeutic utility of liposomes in the local treatment of inflammatory disorders, specifically rheumatoid arthritis (RA). Our purpose was to design a depot delivery system of an anti-inflammatory glycoprotein, lactoferrin (Lf), using positive multivesicular liposomes and to investigate its in vivo efficiency. Lactoferrin (Lf) has previously been shown to have therapeutic potential in mice with collagen-induced arthritis (CIA) after intra-articular (i.a.) injection. In order to protect Lf from enzymatic degradation and to maintain an adequate concentration in the joint, liposomes have been used as carriers for controlled drug delivery. Based on our previous findings we compared the ability of free Lf and Lf encapsulated in liposomes to suppress established joint inflammation and to modulate the cytokine response of lymph node (LN) T lymphocytes in DBA/1 mice with CIA. The anti-inflammatory effect of Lf formulated in positive liposomes was more pronounced compared with the free protein. After a single i.a. injection of liposomal Lf the arthritic score significantly decreased continuously for 2 weeks while in the case of free Lf for only 3-4 days. The cytokine levels produced by LN T cells showed decreased pro-inflammatory cytokines (TNF-agr and IFN-γ) accompanied by increased anti-inflammatory cytokines (IL-5 and especcialy IL-10) in encapsulated compared with free Lf. When compared with free Lf, liposomal Lf decreased the expression of costimulatory molecules on DCs, reduced pro-inflammatory (TNF) and increased anti-inflammatory (IL-10) cytokine production. Using CIA model we have studied the liposome trafficking following i.a. administration and we have identified DCs as a target for liposomes in the draining LN. Our results suggest that the entrapment of Lf in liposomes may modify its pharmacodynamic profile and could have great potential as controlled delivery system in the treatment of RA and other local inflammatory conditions.
LanguageEnglish
Pages237-248
Number of pages11
JournalJournal of Liposome Research
Volume17
Issue number3-4
DOIs
Publication statusPublished - 2007

Fingerprint

Lactoferrin
Nanostructures
Lipids
Liposomes
Experimental Arthritis
Cytokines
Anti-Inflammatory Agents
Intra-Articular Injections
Joints
Lymph Nodes
Interleukin-10
Rheumatoid Arthritis
T-Lymphocytes
Inbred DBA Mouse
Drug Carriers
Interleukin-5
Therapeutics
Arthritis
Glycoproteins

Keywords

  • liposomes
  • lactoferrin
  • rheumatoid arthritis
  • cytokines
  • dendritic cells

Cite this

Brewer, J.M. ; Trif, M. ; Roseanu, A. ; Brock, J.H. / Designing lipid nanostructures for local delivery of biologically active macromolecules. In: Journal of Liposome Research. 2007 ; Vol. 17, No. 3-4. pp. 237-248.
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Designing lipid nanostructures for local delivery of biologically active macromolecules. / Brewer, J.M.; Trif, M.; Roseanu, A.; Brock, J.H.

In: Journal of Liposome Research, Vol. 17, No. 3-4, 2007, p. 237-248.

Research output: Contribution to journalArticle

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AB - This study focuses on the possible therapeutic utility of liposomes in the local treatment of inflammatory disorders, specifically rheumatoid arthritis (RA). Our purpose was to design a depot delivery system of an anti-inflammatory glycoprotein, lactoferrin (Lf), using positive multivesicular liposomes and to investigate its in vivo efficiency. Lactoferrin (Lf) has previously been shown to have therapeutic potential in mice with collagen-induced arthritis (CIA) after intra-articular (i.a.) injection. In order to protect Lf from enzymatic degradation and to maintain an adequate concentration in the joint, liposomes have been used as carriers for controlled drug delivery. Based on our previous findings we compared the ability of free Lf and Lf encapsulated in liposomes to suppress established joint inflammation and to modulate the cytokine response of lymph node (LN) T lymphocytes in DBA/1 mice with CIA. The anti-inflammatory effect of Lf formulated in positive liposomes was more pronounced compared with the free protein. After a single i.a. injection of liposomal Lf the arthritic score significantly decreased continuously for 2 weeks while in the case of free Lf for only 3-4 days. The cytokine levels produced by LN T cells showed decreased pro-inflammatory cytokines (TNF-agr and IFN-γ) accompanied by increased anti-inflammatory cytokines (IL-5 and especcialy IL-10) in encapsulated compared with free Lf. When compared with free Lf, liposomal Lf decreased the expression of costimulatory molecules on DCs, reduced pro-inflammatory (TNF) and increased anti-inflammatory (IL-10) cytokine production. Using CIA model we have studied the liposome trafficking following i.a. administration and we have identified DCs as a target for liposomes in the draining LN. Our results suggest that the entrapment of Lf in liposomes may modify its pharmacodynamic profile and could have great potential as controlled delivery system in the treatment of RA and other local inflammatory conditions.

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