Development of trimethyl chitosan coated nanostructure lipid carriers to enhance the brain targeting capacity of ceftriaxone

Abstract

Cationic nanostructured lipid carriers were devised to improve the biodistribution of the drug in the CNS. Especially, the delivery of antibiotics via uninflamed meninges at various stages of infection is the most challenging part of the treatment regimen. The ceftriaxone loaded nanostructured lipid carriers (NLC-CEFs) were formulated using glyceryl monostearate and capryol90 and the resulting NLC-CEFs were coated with trimethyl chitosan (NLC-CEFs-TMC) to increase the cellular uptake of the drug. The TMC was synthesized from chitosan and its formation was confirmed by XRD, FTIR, DSC, and H1 NMR analyses. The freeze-dried NLC-CEFs and the NLC-CEFs-TMC formed, were evaluated by FTIR, DSC, XRD, SEM, and zeta potential analyses. The rat model was used to study the biodistribution of the drug in brain and confirm the potential delivery of drug in NLC-CEFs-TMC carriers through blood brain barrier. It was found to increase by 10.51 times compared to the drug solution when administered through IV and collected after 8 h. The brain enhancement factor was found to be, 5.86 and 7.95 respectively for NLC-CEFs and NLC-CEFs-TMC collected after 8 h. The brain targeting index was found to be 0.29 ± 0.02, 0.50 ± 0.04 and 0.029 ± 0.007 for NLC-CEFs, NLC-CEFs-TMC, and CEF solution. The highest brain targeting index and brain enhancement ratio was achieved by NLC-CEFs-TMC. Success of these lipid dosage forms may be attributed to the lipophilic nature of the NLCs, which is similar to that of meninges and another cause may be the increase in the uptake of cationic NLCs by negatively charged CNS membrane.

GRAPHICAL ABSTRACT

Keywords:

• brain enhancement ratio
• brain targeting index
• biodistribution surface coating

Disclosure statement

No potential conflict of interest was reported by the authors.