Development and Evaluation of Nanosuspension Loaded Nanogel of Nortriptyline HCl for Brain Delivery

Abstract

Nanogel systems loaded with nanosuspension area promising approach tonose-to-brain delivery in order to reduce the dose and dosing frequency and also improve the bioavailability of the drug. In the present study, an attempt was made to develop a nanosuspension-loaded insitu nasal nanogel of nortriptyline HCl (NTH) to achieve effective administration through the intranasal route to reach the brain via the olfactory and trigeminal nerves to improve the therapeutic efficiency. A nanoprecipitation–ultrasonication method followed by high-pressure homogenization was elected for the preparation of the nanosuspension, which was further incorporated into the in situ gelling polymer solution. The optimized nanosuspension-loaded nanogels were prepared using gellan gum. The optimized formulation showed an average particle size of 10–100 nm, a good PDI value, an increase in solubility, a good gelation property, and the desired viscosity to adhere to the nasal mucosa after ionic interactions. In vitro drug release was found to be greater than a drug solution over a period of 60 min. Spreadability and viscosity studies showed better results in achieving a good residence time. Hence, it was proved that insitu nanogel is one of the best possible approaches for the targeting of drugs toward the brain in nanoform.

Keywords

• brain targeting
• intranasal delivery
• homogenization
• nanosuspension
• insitu gel