Improved brain pharmacokinetics following intranasal administration of N,N,N-trimethyl chitosan tailored mucoadhesive NLCs

ABSTRACT

Here we report the development of tristearin-based nanostructured-lipid carriers (NLCs) which were further surface-modified with mucoadhesive N,N,N-trimethyl chitosan (TMC) to form mucoadhesive nanostructured-lipid carriers (mNLCs). The NLCs were loaded with high partitioning ropinirole-dextran sulphate (ROPI-DS) nanoplex. NLCs were optimised using Box-Behnken experimental design. Obtaining controlled drug release with prolonged residence on the nasal mucosa for treating Parkinson’s disease (PD) is a major objective of the present investigation. Enhanced brain targetability and improved therapeutic efficacy are the additional objective of this study. Lyophilised NLCs and mNLCs were characterised in solid state by FTIR, DSC, XRD, and HR-TEM analysis. The bioadhesive strength of mNLCs was observed to be 13.3-folds greater compared to NLCs. Plasma and brain pharmacokinetic studies in mice model demonstrated the potential of mNLCs in nose-to-brain drug delivery via olfactory pathway. If investigated for behavioural and neurotoxicity studies clinically, a commercial formulation for patient looks feasible.

Graphical abstract

KEYWORDS:

• Nanostructured lipid carriers
• mucoadhesion
• nose-to-brain
• drug delivery
• Parkinson’s disease
• N
• N
• N-trimethyl chitosan

Disclosure statement

No potential conflict of interest was reported by the authors.

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