Objective: Although levodopa is the preferred medication for treating Parkinson’s disease, it has a very poor brain absorption and limited oral bioavailability. The goal of the current study is to decrease dosage requirements and increase bioavailability of leveodopa by developing and evaluating a nasal mucoadhesive microsphere aerosol.

Background: Delivering medications and proteins that are impermeable to the brain to the central nervous system (CNS) by intranasal delivery has become a popular approach. This is because the olfactory route of administration fully avoids the blood brain barrier, and intranasal medication delivery is often well tolerated and noninvasive.

Method: Levodopa was included in the spray-dried and cross-linked microspheres, which were made of mucoadhesive polymers such as sodium alginate, hydroxypropylmethylcellulose, chitosan salt, and hydroxypropylcellulose. Optimisation was done for both formulation and processing factors, such as the drug-to-polymer ratio and stirring speed. Microspheres were assessed for their potential for nasal drug delivery in terms of particle size and in vivo dispersion following intranasal injection, as well as their drug content, swelling ability, percentage yield, and in vitro release properties. Tests were also conducted on the levodopa microsphere aerosol’s effectiveness for striatal transplanting and its ability to modify apomorphine-induced rotating behaviour in a rat model with unilateral 6-hydroxydopamine lesion.

Results: Spray-dried and cross-linked formulations were reported to have an average particle size of 10–30 µm and a percent mucoadhesion of 90%–95%. Drug to polymer ratio was shown to be proportionate to in vitro drug release. After six hours, it was discovered that the in vitro drug release for the optimised formulation, or (F4), was 94.56%. The medication was released from the microspheres according to non-Fickian diffusion kinetics. As early as one week after lesion, microsphere aerosol groups infused with levodopa showed lower rotation scores than microsphere groups. These advantages persisted for the duration of the experiment, and at weeks one, two, and eight they were statistically significant (p<0.001).

Conclusion: Compared to other previously reported delivery methods, the results of this work suggest that intranasal aerosol microsphere of levodopa may be advantageous for the treatment of Parkinson’s disease.

References: Arica B, Kaş HS, Moghdam A, Akalan N, Hincal AA. Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats. J Control Release. 2005 Feb 16;102(3):689-97.
Norman AB, Calderon SF, Giordano M, Sanberg PR. Striatal tissue transplants attenuate apomorphine-induced rotational behavior in rats with unilateral kainic acid lesions. Neuropharmacology. 1988 Mar;27(3):333-6.
Betül Arıca, H. Süheyla Kaş ,A. Atilla HıncalEvaluation and Formulation of Biodegradable Levodopa Microspheres Using 32 Factorial Design. Biomedical Science and Technology pp 41-49|.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spray-with-nasal-mucoadhesive-microspheres-for-treating-parkinsonism/