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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.

Targeted delivery of carmustine (BCNU), an efficient brain tumor therapeutic, has been challenged with bioavailability issues due to the Blood Brain Barrier (BBB). The currently effective delivery approach is by implants at the site of the tumor, but this is highly invasive. The intranasal route, which is non-invasive and bypasses the BBB, may be alternative route for delivering BCNU to the brain. In this work, polyvinyl alcohol/polyethyleneimine/fIuorecein isothiocyanate complex (Polyplex) coated iron-oxide nanoparticles (Magnetite) were synthesized employing co-precipitation, epoxidation and EDC/NHS coupling reactions. The Polyplex coated magnetite (Nano-co-Plex) was loaded with BCNU for potential magnetically targeted delivery to the brain following intranasal administration. The Nano-co-Plex was characterized employing Thermogravimetric analysis (TGA), Superconducting Quantum Interference Device (SQUID) magnetometry, Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X-ray Diffractometry (XRD), Transmission Electron Microscopy (TEM) and Zetasize analysis. Results revealed superparamagnetic hexagonally shaped "core-shell" nanoparticles with cell labeling attributes, of size ranging between 30-50 nm, and a zeta potential value of + 32 ± 2 mV. The Nano-co-Plex synthesized was found to possess high degree of crystallinity with 32% Polyplex coating. The loading and release studies indicated a time-dependent loading with maximum loading capacity of 176.82 μg BCNU/mg of the carrier and maximum release of 75.8% of the loaded BCNU. Cytotoxicity of the BCNU-loaded Nano-co-Plex displayed superiority over the conventional BCNU towards human glioblastoma (HG) cells. Cell studies revealed enhanced uptake and internalization of BCNU-loaded Nano-co-plex in HG cells in the presence of an external magnetic field. These Nano-co-Plexes may be ideal as an intranasal magnetic drug targeting device for BCNU delivery.