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Mucoadhesive Drug Delivery Systems for Nose-to-Brain Targeting of Dopamine

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Abstract:

Drugs can be transported directly from the nasal cavity to the central nervous system via olfactory epithelium thereby bypassing blood-brain-barrier and blood-cerebrospinal fluid barrier. The brain uptake requires nasal formulations and device capable to provide olfactory region deposition, appropriate site permanence and favorable amounts of drug for transport. In this work, an attempt was made to develop mucoadhesive microparticles able to obtain controlled release of dopamine after nasal administration. The design of systems was based on ionic interaction between dopamine and alginate. Electrical conductivity of polymer or drug solutions was measured in order to identify the proper pH conditions useful for achieving optimal charge interaction. Loaded and unloaded microspheres were prepared by spray drying and in-vitro characterized in terms of drug loading, size and size distribution and morphology. The dopamine release from formulations as well as the drug dissolution rate were evaluated in phosphate buffer and simulated nasal electrolyte solution. In-vitro permeation experiments were also carried out. The gelling rate and water uptake of formulations were also assessed. Results show that pH 4 may allow the optimal interaction between alginate and dopamine for the preparation of microspheres. Alginate matrix is able to entrap high amounts of dopamine. Loaded microparticles show similar density and size and therefore comparable aerodynamic features. Particles have an almost spherical shape with several invaginations and rough surface. Microparticles gel very quickly within 3 min but drug loading decreases the water absorption capability of alginate microspheres. Results from in-vitro release and permeation tests highlighted that formulation based on the 1:1 weight ratio shows the best in-vitro profiles.

Keywords: MUCOADHESIVE FORMULATIONS; NASAL ROUTE; NOSE-TO-BRAIN TARGETING; PARKINSON DISEASE; PARTICULATE DRUG DELIVERY SYSTEMS

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jns.2012.1015

Publication date: April 1, 2012

More about this publication?
  • Recent advances in nanomaterials indicates that the central nervous system (CNS) is susceptible to nanoparticle induced alterations leading to functional or structural alterations. This knowledge is currently disseminated in vast array of journals dealing with broad subject areas related to pharmacology, toxicology, neuroscience or nanosciences. Thus, there is an urgent need to collect all these diverse information related to nanoscience and brain function in one place using Journal of Nanoneuroscience for the benefit of the scientific community, researchers, health planners, health care providers, policy makers, environmentalists, biologists, chemists, and physicist in this emerging area of medical science.
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