Objective: The presence of tight junctions in blood-brain barrier creates a major problem for the delivery of drugs and severely affects adequate therapeutic concentration to reach the brain. For the treatment of epilepsy, oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Thus, an alternative route of drug delivery is highly desirable for an effective outcome. Methods: In the present study, bioadhesive chitosan nanoparticles of topiramate for intranasal administration were prepared by ionotropic gelation method using chitosan as bioadhesive polymer and sodium tripolyphosphate as the crosslinking agent. The prepared nanoparticles were evaluated for physicochemical properties like particle size, surface morphology, drug content, entrapment efficiency, thermal behavior and crystallinity, in vitro drug diffusion, ex vivo bio adhesion, and ex vivo biocompatibility studies in excised sheep nasal mucosa. Results: Differential scanning calorimetry and x-ray diffraction study showed molecular dispersion of drug into the polymer matrices and conversion of it into an amorphous form. Nanoparticles obtained were discrete in nature (size 313.5 nm) and appropriate for intranasal administration. The topiramate nanoparticles revealed high encapsulation efficacy, strong bioadhesion potential and high ex vivo permeation and did not exhibit any deformity to the nasal mucosa. In vitro drug diffusion of optimized formulation showed 92.91% release of drugs after 180 min. Ex-vivo permeation of drugs across nasal mucosa was 89.03 % after 180 min. Conclusion: Hence, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.
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