Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes.
The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (Tfs), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that 1 mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis.
Simões
S I
SI
Unidade de Novas Formas de Agentes Bioactivos, Departamento de Biotecnologia, Instituto Nacional de Engenharia, Tecnologia e Inovação, Edifício F, Estrada do Paço do Lumiar, 22 1649-038 Lisboa, Portugal. sandra.simoes@ineti.pt
Delgado
T C
TC
Lopes
R M
RM
Jesus
S
S
Ferreira
A A
AA
Morais
J A
JA
Cruz
M E M
ME
Corvo
M L
ML
Martins
M B F
MB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001205:Ascorbic Acid / Q000097:blood; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005121:Extremities / Q000000981:diagnostic imaging; D007958:Leukocyte Count; D008081:Liposomes; D008297:Male; D010316:Particle Size; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000097:blood; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D008081:Liposomes; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase; D001205:Ascorbic Acid