Page 3 - PROPOSAL LATIP Zanamivir_Neat 2

The elimination of Zanamivir is through kidneys and since the amount systemically

absorbed is low, no dosage adjustment is necessary with renal insufficiency.
Thus, this study will focus on strategizing to enhance the absorption profiles of

Zanamivir and to compare which route of delivery offers better absorption of zanamivir
that would be beneficial in treating influenza-like illness. The nanoparticulate drug

delivery approach is conducted by changing or reducing its particle size, modifying its

surface characteristics and the use of other materials such as excipients in the delivery
system thus the nanoparticles can be developed into a smart system, encasing the drug

(Rizvi & Saleh, 2018). The use of absorption enhancers that help increase the drug
permeability is a frequent practice nowadays. Absorption enhancers include surfactants,

cholesterol, glycerides, salicylates, bile salts, and chelating agents (Aungst, 2012). In

order to increase the solubility of the drug, we should screen the most suitable surfactant
carefully, reduce the particle size, and select the most effective salt if necessary

(Alqahtani et al., 2021).
Therefore, in this study, we aimed to design and formulate a nanoparticulate

delivery system of Zanamivir to improve its oral absorption profiles and to further study
its mechanistic pathways either through paracellular or intracellular pathways. This study

includes evaluating the physicochemical properties of Zanamivir nanoparticles by

conducting particle size analysis, polydispersity index (PDI), zeta potential,
morphological observation (scanning electron microscope (SEM) and Transmission

electron microscope (TEM)), Fourier-transform infrared spectroscopy (FTIR), X-ray
diffraction (XRD) analysis, Caco-2 cell permeation as well as in vitro drug release and

drug content study and its efficacy in ex vivo and in vivo rat animal model. In addition,

the mechanism of action of how Zanamivir permeates across the intestinal linings will be
examined via transepithelial electrical resistance (TEER) analysis.

1.2 Problem statement

Until now, oral delivery of Zanamivir has been a problem due to its strong

hydrophilic nature that limits its transport across the intestinal epithelium (Li et al., 1998;
von Itzstein, 2007; Miller et al., 2010). The absolute bioavailability of Zanamivir is very

low (2%) orally and is 4% to 17% through oral inhalation (Zanamivir: Uses, Interactions,
Mechanism of Action | DrugBank Online, 2020).