Objective: Levodopa is the drug of choice in the treatment of Parkinson’s disease but it exhibits low oral bioavailability and very low brain uptake. The present research work involves formulation development and evaluation of nasal mucoadhesive microsphere aerosol of leveodopa in view to, improve bioavailability and reduce dosing regimen.

Background: The intranasal route of administration has emerged as an attractive method for delivering brain impermeable drugs and proteins to the CNS. This is because intranasal drug administration is generally well tolerated, noninvasive, and because the olfactory route of administration completely bypasses the blood brain barrier.

Method: The Microspheres were prepared by spray drying and cross-linking method using mucoadhesive polymers including chitosan salt, hydroxypropylmethylcellulose, sodium alginate and contained levodopa. Formulation parameters and processing parameters like ratio of drug to polymer and stirring speed were optimized. Microspheres were evaluated for particle size, drug content, swelling ability, percentage yield, In Vitro release characteristics and suitability for nasal drug delivery in terms of particle size and in vivo distribution after intranasal administration. The efficiency of levodopa microspheres aerosol to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine unilaterally lesioned rat model were also tested.

Results: The average particle size of spray-dried and cross-linked formulations were found in the range between 10-30 µm with percent mucoadhesion in the range of 90%-95%. In vitro drug release was found to be proportional to drug to polymer ratio. In vitro drug release for optimized formulation, that is, (F4), was found to be 94.56% at the end of 6 h. Release of drug from microspheres followed non-Fickian diffusion kinetics. Levodopa loaded microsphere aerosol groups exhibited lower rotation scores than microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks. The histopathological study indicates nonirritant nature of microsphere.

Conclusion: The results of this work indicate that intranasal aerosol microsphere of levodopa may be beneficial for the treatment of Parkinson’s disease compared with other delivery routes reported earlier.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/design-characterization-and-in-vivo-evaluation-of-intranasal-delivery-of-levodopa-loaded-microspere-for-parkinsonism/