*4.4.4 Protein drug delivery*

Proteins are the building blocks of life and required in replicating organisms. Their high molecular weight, chemical and enzymatic susceptibility in the GIT, low diffusion rate through the mucosa barrier and fast systemic clearance, limit their delivery via oral route. As a result, most proteins are administered parenterally. Fortunately, chitosan-based NP are emerging as promising means for the delivery of protein drugs by the oral route through a combination of shielding GI pH, enzymatic degradation and facilitation of epithelial uptake [117]. In a study by He et al., chitosan-STPP insulin NP (CS/STPP/insulin) were orally administered to Type I diabetic rat models in comparison to free insulin solution. Free insulin solution failed to elicit any difference in the blood glucose level, whilst CS/STPP/insulin NP distinctly reduced the blood glucose levels by up to 59% within 8 hours. Crucially, CS/TPP/ insulin NP allowed for a fast recovery of blood sugar level when fasting was halted. Moreover, the CS/TPP/insulin NP exhibited negligible toxicity to liver enzymes, confirming the safety profile of the orally delivered CS/TPP/insulin NP. They concluded that CS/TPP NP are an effective oral delivery vehicle for insulin [118]. In another study, Tan et al. demonstrated better *in vitro* uptake and safety profile from amphotericin B-containing chitosan coated nanostructured lipid carrier (ChiAmpB NLC) than from uncoated NLC [119]. The same authors later demonstrated better *in vivo* uptake from ChiAmpB NLC in rats than from uncoated NCL [120]. They attributed the observed increase in systemic bioavailability to increased mean absorption and mean residence times (MAT and MRT) from ChiAmpB NLC than from naked NLC. This was prompted by the mucoadhesive effect imposed by chitosan.
