Ketoprofen-loaded rose hip oil nanocapsules attenuate chronic inflammatory response in a pre-clinical trial in mice.

This study aimed to develop nanocapsules containing ketoprofen using rose hip oil (Keto-NC) as oil core, and to evaluate their anti-inflammatory activity in acute and chronic ear edema models in mice. Physicochemical characterization, drug release, photostability and cytotoxicity assays were performed for the developed Keto-NC formulations and compared to ketoprofen-loaded nanocapsules using medium chain triglycerides as oil core (Keto-MCT-NC). Anti-inflammatory activity of orally delivered KP (Ketoprofen-free; 10 mg.kg-1) or Keto-NC (2.5; 5; 10 mg.kg-1) was assessed in mouse acute and chronic ear edema induced by croton oil (CO). Edema histological characteristics were determined by H&E stain, and redox parameters were analyzed in blood plasma and erythrocytes. Keto-MCT-NC and Keto-NC did not exhibit differences regarding physicochemical parameters, including size diameters, polydispersity index, pH, Ketoprofen content, and encapsulation efficiency. However, Keto-NC, which contains rose hip oil as lipid core, decreased drug photodegradation under UVC radiation when compared to Keto-MCT-NC. KP or Keto-NC were not cytotoxic to keratinocyte cultures and produced equal edema inhibition in the acute protocol. Conversely, in the chronic protocol, Keto-NC was more effective in reducing edema (~60-70% on 7-9th days of treatment) when compared to KP (~40% on 8-9th days of treatment). This result was confirmed by histological analysis, which indicated reduction of edema and inflammatory infiltrate. A sub-therapeutic dose of Keto-NC (5 mg.kg-1) significantly reduced edema when compared to control. Finally, KP and Keto-NC exhibited similar effects on redox parameters, suggesting that the advantages associated with Ketoprofen nanoencapsulation did not involve oxidative stress pathways. The results showed that Keto-NC was more efficient than KP in reducing chronic inflammation. These data may be important for the development of strategies aiming treatment of chronic inflammatory diseases with fewer adverse effects.

High frequency of iron bone deposits in a Mexican population with renal osteodystrophy.

Renal osteodystrophy (ROD) is a multifactorial disease. Aluminium deposits have been implicated in its physiopathology but iron deposits have seldom been described. The purpose of this study was to investigate the presence of iron on the mineralization front, in 70 patients with ROD. Their mean age was 48+/-16 years, 36 were female, 34 male, 55 were admitted on peritoneal dialysis (78.5%) and 15 to haemodialysis (21.5%), for a period of 28+/-22 months. A bone biopsy was obtained from each patient after double tetracycline labelling. Blood samples were also obtained at the time of bone biopsy. The histomophometric analysis was performed following the criteria of Sherrard et al., with slight modifications; beside the usual stains, aluminium, iron and amyloid stainings were done on all bone specimens. Biochemical findings were: Ca 8.8+/-0.9 mg/dl, P 6.1+/-1.5 mg/dl; total alkaline phosphatase 197+/-258; PTHm 4.9+/-4.05ng/ml (normal 0.4-0.7 ng/ml), calcitonin 11+/-6 pg/ml (normal 1-26 pg/ml). Osteitis fibrosa was found in 31 patients (44.28%), mixed bone disease in two patients (2.28%); mild bone disease in 20 subjects (28.57%), adynamic bone lesion in 15 cases (21.42%) and osteomalacia in two patients (2.28%). Iron deposits were found on the mineralization front in 43 patients (61.4%); in 17, the percentage was <25 and, in 26, >25%. The iron deposits in the osteitis fibrosa group were highly significant (25/31). The aluminium deposit at the mineralization front was observed in eight patients (11.4%); in all but one, the percentage of this metal was <10%. Amyloid deposits were negative in all cases. The results show: (i) a Mexican population with ROD, present a highly significant incidence of siderosis on the bone mineralization front; (ii) in contrast, the aluminium deposits in this group of patients is lower than that reported in other series, and (iii) the spectrum of RO in this Mexican population is similar to that reported in other studies.