Nanostructured Drug Loaded Lipids for Management of Meningitis

Abstract

The brain and spinal cord together form the central nervous system. In case of uninflamed meninges the penetration of drug moiety is reduced drastically and this condition occurs at the early stage of disease or when the disease is at the verge of cure. Hence it is required that even in uninflamed condition the drug should be available in the brain tissue at sufficient concentration to combat the infection. In this research, experimental work focuses on the development of ceftriaxone loaded NLCs coated with trimethyl chitosan. The main purpose of this experiment is the effective management of meningitis by increasing its penetration ability across the brain tissue mainly during the early phase of infection and in the recovery phase of infection. Ceftriaxone is hydrophilic drug having very low penetration through the uninflamed meninges and the AUC ratio of ceftriaxone in CNS to that in serum, is nearly 0.007 which is extremely low. Therefore to maintain the minimum inhibitory concentration more amount of drug has to be administered which may increase the toxicity of the drug. Insufficient amount of ceftriaxone in CNS also lead to development of resistance against the antibiotic. In this experiment the optimized formulations are coated with positively charged TMC hence it is necessary to conduct toxicity studies to find out the toxic effect of the new formulation on the rodents. Some reports in available literature indicate toxic effects of cationic polymers it is imperative that acute toxicity and sub chronic toxicity studies were conducted. Biodistribution studies were conducted for 50 mg kg body weight dose of ceftriaxone. Both NLCCEFs and NLCCEFsTMC showed significant difference compared to ceftriaxone solution. The concentration of drug in CNS was increased on administration of NLC CEFs and NLCCEFsTMC by almost 7.9 and 10.51 times respectively after 8 h IV administration. newline