Nose to brain delivery of escitalopram-loaded nano-structured lipid carriers thermosensitive gel: Formulation, physiochemical, pharmacokinetic and pharmacodynamics evaluation

Abstract

The primary focus of the undertaken research was to design and develop poloxamer-based thermosensitive gel system of escitalopram-loaded nano-structured lipid carriers (ESC-NLCs gel) for nose to brain delivery. ESC-NLCs were optimized using Design Expert® (Version 12). The optimized formulation was encompassed in poloxamer-based thermosensitive gel and was characterized accordingly. In vitro release, ex vivo permeation and in vivo brain and plasma pharmacokinetics was investigated. Additionally, behavioral analysis of the lipopolysaccharide (LPS) induced depressed rats was performed followed by immunohistochemistry of the brain hippocampus and cortex regions. Particle size, polydispersity index and zeta potential of the optimized ESC-NLCs were respectively found as 131 nm, 0.278 and −24.9 mV with excellent entrapment efficiency (96 %). The optimized formulation showed suitable morphology, optimum thermal behavior, amorphous nature and drug-excipient compatibility. ESC-NLCs gel displayed sustained in vitro release profile, whereas permeation was enhanced 27-folds. Brain pharmacokinetics of ESC-NLCs explored 9 folds increased drug concentration in brain. Similarly, improved behavioral changes and reduced neuro inflammatory markers (NF-κB and TNF-α) were observed in LPS induced depressed rats after treatment with ESC-NLCs gel. It can be concluded that ESC-NLCs gel has the potential to sustain the drug release, improve the permeation and bioavailability and reduce the depression after nose to brain delivery in animal model.