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In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN)

Journal

PHARMACEUTICALS
Volume 14, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/ph14080711

Keywords

nasal administration; nanostructured lipid carriers; solid lipid nanoparticles; in vitro cell cultures; 3D nasal casts

Funding

  1. FundacAo para a Ciencia e a Tecnologia (FCT) (Portugal) [SFRH/136177/2018]
  2. Applied Molecular Biosciences Unit-UCIBIO - FCT [UIDP/04378/2020, UIDB/04378/2020]
  3. CIBB (FCT) [UIDB/04539/2020]

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The nasal route has long been used for treating nasal diseases, but recent research suggests its potential for targeting the central nervous system through the use of lipid nanoparticles in nasal formulations. In vitro studies and the use of 3D nasal casts are proving to be effective in assessing drug transport mechanisms and predicting drug deposition in the nasal cavity. Further in vivo studies are still necessary, but the use of 3D nasal casts presents a promising avenue for research.
The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood-brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research.

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