Intranasal mucoadhesivemicroemulsion for neuroprotective effect of curcuminin mptp induced Parkinson model

ABSTRACT This study was to investigate the neuroprotective effect of curcumin against inflammation-mediated dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease (PD). Curcumin loaded sodium hyaluronate based mucoadhesive microemulsion (CMME) was developed by using Box Behnken design of Response surface method (RSM) and was characterized. Male C57BL/6 mice were first treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals followed CMME intranasal administration for 14 days at 2.86 mg of curcumin/kg of body weight per once a day. Optimal CMME containing 3% Capmul MCM as oil phase, 37 % of Accenon CC and Transcutol HP at 2.5:1 ratio and 0.5% sodium hyaluronate was stable, non-ciliotoxic with 57.66 nm±3.46 as average globule size. PdI value (0.190 ± 0.19) and TEM result depicted the narrow size distribution of CMME.All three independent variables had a significant effect (p<0.05) on the responses and the designed model was significant for all taken responses. In-vivo results revealed significant reduction of MPTP-mediated dopamine depletion after nasal administration of CMME. MPTP intoxication significantly decreased striatal DA content to 21.29 % which was then elevated to 55.37% after intranasal curcumin treatment. Significant improvement in motor performance as well as gross behavioural activity of mice was observed from rota-rod and open field test findings. Findings of the investigation revealed the symptomatic neuroprotection of curcumin against MPTP-induced neurodegradation in the striatum and hence could be considered as a promising approach to treat PD.

Smokers versus snorters: do treatment outcomes differ according to route of cocaine administration?

Smoking cocaine achieves maximal concentration and effect far more rapidly than through the intranasal ("snorting") route, and it is associated with greater propensity for dependence and more severe consequences. However, very little is known about differences in treatment outcome according to route of administration. This study compared treatment outcomes, such as frequency of cocaine use and Addiction Severity Index (ASI) composite scores, by primary route of cocaine administration (smoking vs. intranasal) among a pooled sample of 412 cocaine-dependent individuals participating in 1 of 5 randomized clinical trials. The majority (80%) reported smoking as their primary route of cocaine administration. Overall, results indicated better cocaine use outcomes both during the treatment phase and through a 12-month follow-up period for intranasal users compared to smokers, although not all differences reached statistical significance. Intranasal users remained in treatment longer, F(1, 408) = 3.55, p < .05, and showed a trend toward achieving longer periods of sustained abstinence within treatment, F(1, 378) = 2.68, p = .08, as well as less use over time during the follow-up period than smokers (Time × Route: t = 1.87, p = .06). Also, intranasal users' ASI cocaine composite score decreased more than smokers, but there were overall decreases in the other ASI domains for all participants over the course of the study period. These results suggest that intranasal users may achieve better cocaine use outcomes than smokers, yet this doesn't appear to translate to differential changes in the severity of problems experienced in other life areas.

A survey of intranasal medication use in the paediatric emergency setting in England and Wales.

For analgesia and sedation in the paediatric setting, intranasal medication is favourable for several reasons, in particular ease of administration and rapid onset of action. A survey was conducted of all Emergency Departments in England and Wales regarding their use of intranasal medication in children. Approximately 50% use intranasal medication, commonly intranasal diamorphine with sporadic use of other opiates. Intranasal midazolam is used for sedation but is less well tolerated than when administered orally. Intranasal diamorphine, however, is safe and effective in the management of pain in the paediatric emergency setting and its ease of administration makes it ideal for use in the already traumatised child.