N,N,N‑trimethyl chitosan modified flaxseed oil based mucoadhesive neuronanoemulsions for direct nose to brain drug delivery

Abstract Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were further surface-modified with a mucoadhesive polymer, N , N , N ‑trimethyl chitosan (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated using hot high-pressure homogenization (HPH) technique. NNEs were optimized using Central Composite experimental design. TMC modified mNNE have not been prepared yet for direct nose to brain drug delivery. Here, an objective to provide controlled drug release with prolonged residence on the nasal mucosa for the treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain targeting through BBB bypass drug delivery, improved therapeutic efficacy through enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose and frequency of administration, and safety were further expected outcomes of this experiment. The mNNE formulation was subjected to 6 month stability assessment. The mNNE formulation was administered to the Swiss albino mice model via intranasal route and both, the plasma and brain pharmacokinetics were estimated. The in vivo studies performed on mice exhibited high brain targeting efficiency of mNNE formulation through nose to brain delivery via olfactory pathway. The prepared intranasal mNNEs could be on the clinics, if investigated more for behavioral and neurotoxicity studies.