Abstract
The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM). Bilayer properties and mucoadhesive behavior were investigated by fluorescence studies and DLS analyses, respectively. Changes in vesicle size and ζ-potential values were shown after addition of chitosan glutamate to niosomes, and when in contact with mucin solution. In particular, interactions with mucin were observed in both drug free and pentamidine loaded niosomes regardless of the presence of the coating. The characteristics of the proposed systems, such as pentamidine entrapment and mucin interaction, show promising results to deliver pentamidine or other possible drugs to the brain via nasal administration.
Highlights
Intranasal (IN) drug delivery has been attracting a lot of interest recently due to its potential to bypass hepatic first pass metabolism and the blood–brain barrier (BBB), which is formed by brain endothelial cells with tight junctions, and separates systemic blood circulation and cerebrospinal fluid [1,2,3]
Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were studied by atomic force microscopy (AFM)
The niosome samples were tested for their size, ζ-potential, and polydispersity index (PDI) using dynamic light scattering analyses
Summary
Intranasal (IN) drug delivery has been attracting a lot of interest recently due to its potential to bypass hepatic first pass metabolism and the blood–brain barrier (BBB), which is formed by brain endothelial cells with tight junctions, and separates systemic blood circulation and cerebrospinal fluid [1,2,3]. Drugs using other non-invasive delivery methods pass through BBB by paracellular or transcellular pathway, whereas IN delivery has three possible pathways to deliver drugs from nasal cavity to the brain: systemic pathway, olfactory nerve pathway, and trigeminal pathway [3]. Drug molecules enter the brain by diffusing into blood in the large nasal vesicular network, and pass through BBB. Hydrophilic drugs and large molecular weight molecules are inefficiently transported via this pathway, due to the highly selective nature of BBB. Hydrophilic drugs can be possibly delivered into brain through olfactory and trigeminal nerve pathways. The major drawbacks of this delivery method are the mucocillary clearance and enzymatic degradation in the nasal cavity, which reduce the drug bioavailability
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