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The purpose of this work was to develop an in situ thermosensitive electro-responsive mucoadhesive gel loaded with bioactive agent (nanocomposite) meant for nose to brain delivery in a controllable manner when electric stimulation is applied. Nanocomposite was developed using a combinatorial blending of chitosan, hydroxypropylmethylcellulose, pluronic F127 and polyaniline which was then loaded with BCNU-Nano-co-Plex (the bioactive agent). The nanocomposite was a liquid at room temperature but formed an in situ mucogel at a temperature of 27.5 ± 0.5 °C. Furthermore, the nanocomposite possessed a redox element which makes it responsive to electrical stimulation (ES). The stimuli responsiveness enabled the formulation to release the bioactive agent when electrical potential was applied and demonstrated a desired 10.28% release of nanoparticles per application cycle. The results further revealed pore formation within the formulation which accommodated the loaded nanoparticles. The release profile also demonstrated a pulsatile release of the bioactive material when subjected to ES. This formulation may therefore be useful as a nose to brain drug delivery system that can be modulated to deliver bioactive agents to the brain via electro-actuation in an “on-off” drug release kinetics by means of an external ES for a controlled nose-to-brain delivery.

Alzheimer's disease (AD) is known to be caused by the accumulation of deformed beta amyloid and hyperphosphorylated tau proteins resulting into formation and aggregation of senile plaques and neurofibrillary tangles in the brain. Additionally, AD is associated with the accumulation of iron or metal ions in the brain which causes oxidative stress. Galantamine (Gal) is one of the therapeutic agents that has been approved for the treatment of AD, but still saddled with numerous side effects and could not address the issue of iron accumulation in the brain. The use of metal chelators to address the iron accumulation has not been successful due to toxicity and inability to address the aggregation of the plaques. We therefore hypothesize a combinatorial antioxidant–metal–chelator approach by formulating a single dosage form that has the ability to prevent the formation of free radicals, plaques and accumulation of iron in the brain. This can be achieved by conjugating Gal with apo‐lactoferrin (ApoLf), a natural compound that has high binding affinity for iron, to form an apo‐lactoferrin–galantamine proteo‐alkaloid conjugate (ApoLf–Gal) as a single dosage form for AD management. The conjugation is achieved through self‐assembly of ApoLf which results in encapsulation of Gal. ApoLf changes its conformational structure in the presence of iron; therefore, ApoLf–Gal is proposed to deliver Gal and pick up excess iron when in contact with iron. This strategy has the potential to proffer a dual neuroprotection and neurotherapeutic interventions for the management of AD.