| Effects of 15d-PGJ₂-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation. | |
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MedLine Citation:
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PMID: 20883476 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: The PPAR-γ agonist 15d-PGJ₂ is a potent anti-inflammatory agent but only at high doses. To improve the efficiency of 15d-PGJ₂, we used poly(D,L-lactide-co-glycolide) nanocapsules to encapsulate it, and function as a drug carrier system. The effects of these loaded nanocapsules (15d-PGJ₂-NC) on inflammation induced by different stimuli were compared with those of free 15d-PGJ₂. EXPERIMENTAL APPROACH: Mice were pretreated (s.c.) with either 15d-PGJ₂-NC or unloaded 15d-PGJ₂ (3, 10 or 30 µg·kg⁻¹), before induction of an inflammatory response by i.p. injection of either endotoxin (LPS), carrageenan (Cg) or mBSA (immune response). KEY RESULTS: The 15d-PGJ₂-NC complex did not display changes in physico-chemical parameters or drug association efficiency over time, and was stable for up to 60 days of storage. Neutrophil migration induced by i.p. administration of LPS, Cg or mBSA was inhibited by 15d-PGJ₂-NC, but not by unloaded 15d-PGJ₂. In the Cg model, 15d-PGJ₂-NC markedly inhibited serum levels of the pro-inflammatory cytokines TNF-α, IL-1β and IL-12p70. Importantly, 15d-PGJ₂-NC released high amounts of 15d-PGJ₂, reaching a peak between 2 and 8 h after administration. 15d-PGJ ₂ was detected in mouse serum after 24 h, indicating sustained release from the carrier. When the same concentration of unloaded 15d-PGJ₂ was administered, only small amounts of 15d-PGJ₂ were found in the serum after a few hours. CONCLUSIONS AND IMPLICATIONS: The present findings clearly indicate the potential of the novel anti-inflammatory 15d-PGJ₂ carrier formulation, administered systemically. The formulation enables the use of a much smaller drug dose, and is significantly more effective compared with unloaded 15d-PGJ₂. |
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Authors:
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Cf Alves; Nfs de Melo; Lf Fraceto; Dr de Araújo; Mh Napimoga |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 162 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-13 Completed Date: 2011-07-26 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 623-32 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Laboratory of Biopathology and Molecular Biology, University of Uberaba, Uberaba, Brazil. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*, blood, chemistry, therapeutic use Biocompatible Materials* Carrageenan Cytokines / analysis Drug Carriers Hemoglobins / analysis Immunization Inflammation / drug therapy* Lactic Acid* Lipopolysaccharides / immunology Male Mice Mice, Inbred BALB C Nanocapsules Neutrophil Infiltration Neutrophils / immunology Particle Size Peritonitis / drug therapy Polyglycolic Acid* Prostaglandin D2 / administration & dosage, analogs & derivatives*, blood, chemistry, therapeutic use Serum Albumin, Bovine / immunology |
| Chemical | |
Reg. No./Substance:
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0/15-deoxyprostaglandin J2; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Biocompatible Materials; 0/Cytokines; 0/Drug Carriers; 0/Hemoglobins; 0/Lipopolysaccharides; 0/Nanocapsules; 0/Serum Albumin, Bovine; 0/methylated bovine serum albumin; 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 41598-07-6/Prostaglandin D2; 50-21-5/Lactic Acid; 9000-07-1/Carrageenan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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