title: Evaluation of the pro-inflammatory potential of nanostructured drug carriers in knee-joints of rats: effect on nociception, edema, and cell migration.
abstract: Nanocarriers have been developed aiming at drug delivery; however, the irritating effects of these nanoparticles on naïve or inflamed articular tissues are not known. Poly(D,L-lactide) (N-PLA), methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (N-PEG-PLA), and Dynasan 116 (SLN) were used to prepare the nanocarriers. The average diameter (nm) and zeta potential (mV) of these particles were, respectively, 251 and -33.2, 169 and -22.1, and 105 and -13.0. Naive or carrageenan-primed knee-joints received 100 microL of nanoparticle suspensions or control solution. Incapacitation and articular diameter were determined hourly. Synovial leukocytes were counted 6 h after nanoparticle injection. N-PLA increased the articular diameter and leukocytes, but did not cause incapacitation. In primed knee-joints, N-PLA caused incapacitation, and increased the articular diameter and leukocytes. SLN did not produce inflammatory signals either in naive or primed knees. In primed knee-joints, N-PEG-PLA presented an intermediate effect characterized by an increase in the articular diameter, and a slight increase of leukocytes, but not incapacitation. These results suggest that solid lipid nanoparticles may be safer than polymeric ones, which may be correlated to their chemical composition and superficial charge.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, PO Box 476, Florianópolis, SC 88040-900, Brazil.
authors.forename: Tatiany Jovita
authors.initials: TJ
authors.lastname: de Faria
authors.forename: Eduardo
authors.initials: E
authors.lastname: Souza-Silva
authors.forename: Daniel Teixeira
authors.initials: DT
authors.lastname: de Oliveira
authors.forename: Elenara Lemos
authors.initials: EL
authors.lastname: Senna
authors.forename: Carlos Rogério
authors.initials: CR
authors.lastname: Tonussi
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002351:Carrageenan; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced* / Q000473:pathology; D004563:Electrochemistry; D005260:Female; D006614:Hindlimb / Q000473:pathology; D007596:Joints / Q000473:pathology*; D053758:Nanoparticles; D049329:Nanostructures; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects
chemical_list: D000700:Analgesics; D004337:Drug Carriers; D002351:Carrageenan