Formulation and evaluation of carnosic acid nanoparticulate system for upregulation of neurotrophins in the brain upon intranasal administration

Abstract

To develop formulations of carnosic acid nanoparticles and to assess their in vivo efficacy to enhance the expression of neurotrophins in rat model. Carnosic acid loaded chitosan nanoparticles were prepared by ionotropic gelation technique using central composite design. Response surface methodology was used to assess the effect of three factors namely chitosan concentration (0.1–1% w/v), tri-poly phosphate concentration (0.1–1% w/v) and sonication time (2–10 min) on the response variables such as particle size, zeta potential, drug encapsulation efficiency and drug release. The neurotrophins level in the rat brain upon intranasal administration of optimized batch of carnosic acid nanoparticles was determined. The experimental values for the formulation were in good agreement with those predicted by the mathematical models. A single intranasal administration of the optimized formulation of carnosic acid nanoparticles was sufficient to result in comparable levels of endogenous neurotrophins level in the brain that was almost on par with four, once a day intranasal administration of solution in rats. The results clearly demonstrated the fact that nanoparticulate drug delivery system for intranasal administration of carnosic acid would require less number of administrations to elicit the required pharmacological activity owing to its ability to localize on the olfactory mucosal region and provide controlled delivery of carnosic acid for prolonged time periods.

Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, Caspases and NF-κB signaling pathway in mice

“…The aniamls were injected with 10 mg/kg or 20 mg/kg carnosic acid nanoparticles for five days. The carnosic acid nanoparticles were prepared according to previous study [10]. Briefly, carnosic acid nanoparticles were developed by ionotropic gelation technique using response surface Histopathological changes of liver tissue samples with H&E staining.…”

Upregulation of Akt/NF-κB-regulated inflammation and Akt/Bad-related apoptosis signaling pathway involved in hepatic carcinoma process: suppression by carnosic acid nanoparticle

“…The CA nanoparticles were prepared according to a previous study. 24 Briefly, CA nanoparticles were developed by ionotropic gelation technique …”

“…21,22 In addition, a study has found that nanoparticulate drug delivery system for CA intranasal administration needed less amounts of administrations to induce the required pharmacological reaction due to its ability to locate on the olfactory mucosal region and supply controlled CA delivery for prolonged time periods. 23,24 Generally, for the potential antiinflammatory and pro-apoptosis of CA in cancer cells and easier absorbance of nanoparticles, CA nanoparticles could be used as a candidate, which is likely to improve anticancer effects. And the focus will be on evaluating the effect of CA nanoparticles on liver cancer cells in vitro and in vivo experiments through regulating inflammation response and apoptosis.…”

Recent Updates in the Formulation Strategies to Enhance the Bioavailability of Drugs Administered via Intranasal Route

“…Use of vasoconstrictors to reduce the clearance in to the blood and treatment with inhibitors of the efflux transporters reduces the clearance in to the blood and enhances the drug to the CNS. Vaka et al investigated the capabilities of carnosic acid nanaoparticular systems to enhance the in vivo efficacy of carnosic acid and enhance the neurotropin expression in the brain [48][49][50]. It was reported that intranasal administration of carnosic acid nanoparticles resulted in comparable levels of endogenous neurotrophins level in the brain that was equivalent to the four, once a day intranasal administration of solution in rats and demonstrated the fact that nanoparticulate drug delivery system for intranasal administration of carnosic acid reduces the number of administrations to elicit the required pharmacological activity.…”