Effects of 15d-PGJ₂-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation.
OBJECTIVE
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.


METHODS
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).


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
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.
Alves
Cf
C
Laboratory of Biopathology and Molecular Biology, University of Uberaba, Uberaba, Brazil.
de Melo
Nfs
N
Fraceto
Lf
L
de Araújo
Dr
D
Napimoga
Mh
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D001672:Biocompatible Materials; D002351:Carrageenan; D016207:Cytokines / Q000032:analysis; D004337:Drug Carriers; D006454:Hemoglobins / Q000032:analysis; D007114:Immunization; D007249:Inflammation / Q000188:drug therapy*; D019344:Lactic Acid; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D010316:Particle Size; D010538:Peritonitis / Q000188:drug therapy; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D012710:Serum Albumin, Bovine / Q000276:immunology
C477819:15-deoxyprostaglandin J2; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D016207:Cytokines; D004337:Drug Carriers; D006454:Hemoglobins; D008070:Lipopolysaccharides; D053769:Nanocapsules; C029180:methylated bovine serum albumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D002351:Carrageenan; D015230:Prostaglandin D2