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Intranasal Drug Delivery

Intravenously administered drugs may undergo metabolism by the liver and other tissues in conjunction with absorption by peripheral tissues after reaching systemic circulation leading to undesirable side effects. In contrast, intranasal drug delivery represents a safe and effective technique for the delivery of therapeutics into the CNS by a pathway bypassing the BBB [43].

The olfactory epithelium in the nasal cavity is hereby utilized for direct delivery of therapeutic agents into the CNS. The primary mechanism of intranasal absorption is entry of the drug into the olfactory bulb through the olfactory epithelium. Once the drug reaches the olfactory bulb, it diffuses through the olfactory and trigeminal nerves thus effectively distributing the drug throughout the brain. One of the prime advantages of intranasal delivery is that the therapeutic agent can be administered in form of a liquid or aerosol even in an outpatient setting [44].

Intranasal drug delivery appears to be a safe and effective method for drug transport into the CNS. This method has several applications in preclinical as well as clinical setups. Intranasal delivery of insulin in clinical trials has shown to improve cognitive functions [45]. An improvement from deficient to normal insulin levels in the CNS of patients with Alzheimer disease was also demonstrated. Additionally, intranasal oxytocin was shown to improve social and emotional functions in patients with autism spectrum disorder suggesting the effectiveness of intranasal drug delivery [46,47].

Several approaches including mucoadhesive microparticle carriers are being developed to enhance adhesion and retention time of therapeutic agents in the olfactory epithelium. Application of these mucoadhesive carriers resulted in controlled release of dopamine into the CNS suggesting a possible role in the treatment ofdiseases such as Parkinson. However, only a small fraction of dose is able to diffuse through the olfactory epithelium [48,49]. Therefore research is now focused on other delivery strategies that can enhance diffusion across the olfactory epithelium.

 
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