RESUMO
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.
Assuntos
Analgésicos/farmacologia , Portadores de Fármacos/toxicidade , Edema/induzido quimicamente , Articulações/patologia , Analgésicos/química , Animais , Carragenina , Movimento Celular/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Portadores de Fármacos/química , Edema/patologia , Eletroquímica , Feminino , Membro Posterior/patologia , Nanopartículas , Nanoestruturas , Tamanho da Partícula , Ratos , Ratos Wistar , Líquido Sinovial/citologia , Líquido Sinovial/efeitos dos fármacosRESUMO
PURPOSE: The aim of this work was to evaluate the pulmonary antimetastatic activity and the systemic toxicity of camptothecin-loaded microspheres. METHODS: PCL microspheres containing camptothecin (CPT) were prepared by the emulsion solvent/evaporation method and characterized according to their encapsulation efficiency, particle size, morphology, and drug release. The ability of CPT to inhibit the lung metastasis was verified using an experimental mouse model intravenously injected with metastatic B16- F10 melanoma cells. The microspheres and the free drug were given intraperitoneally at a dose of 7 mg/kg at intervals of three or five days for 24 days. The systemic toxicity of CPT was evaluated by weight measurements, survival and hemograms of the animals. RESULTS: The encapsulation efficiency was nearly 80%. The drug release was complete after 72 hours, but the burst effect increased from 7% to 35% with the increase in CPT content in the particles. It was observed during the in vivo essays that all groups treated with CPT had a decrease of nearly 70% in the number of lung metastases. However, systemic toxicity was verified in animals that received the free drug. CONCLUSION: Camptothecin-loaded microspheres demonstrated similar therapeutic efficacy when compared to those of the free drug, but the toxicity was significantly reduced.