**1. Introduction**

According to the US National Institute of Health, drug delivery is a process that permit the influx of therapeutic substances in to the body. Drug delivery systems are designed to enhance the efficiency and safety of therapeutics by regulating the rate, time and place of release in the body [1, 2]. Drug delivery technology has emerged as an essential tool for the improvement of drug bioavailability, reduction in the side effects of medication, all of which generate remarkable clinical outcomes [3]. Drugs may be administered to the body via local application, enterally or parenterally. The parenteral route typically relates to administration that excludes absorption from the gastrointestinal tract (GIT). It consists of administration by injection, inhalation and via transdermal routes. The enteral route is associated with the absorption of the drug via the GIT, this includes oral, sublingual, and rectal administration. Aptly, the mode of drug administration depends on the disease, the desired therapeutic effect and the nature of the product available [4]. Moreover, each delivery route has inherent benefits and constraints. Nevertheless, the majority of manufactured medicines in the pharmaceutical industry are delivered orally, owing to the distinctive advantages offered by this route, including versatility in

accommodating various types of drugs, simplicity of administration and accessibility, patient compliance and safety profiles [5–7]. Additionally, the intestinal epithelium is an ideal platform for drug absorption due to the viscous mucosal layer lined with abundant enterocytes, goblet cells, and Peyer's patches that trap drug molecules within the mucus as they transit the GIT. [8, 9].

In comparison to other routes of administration, the oral route is exceptionally complex in expression of anatomical features physiology throughout the GIT [10]. Furthermore, these expressions vary along the GIT in both intensity structure. For example, the mucus layer varies in composition and physical properties along the GIT and the pH varies significantly in the main sections of the GIT. The gastrointestinal motility also varies in intensity and form along the GIT and also depends on food status [11]. Even though, these features can impede drug delivery across the GIT, through careful interplay between formulation science and GIT physiology, scientists have been able to exploit this variance for improved drug delivery. In this regard, nanoparticle formulations have immerged as strong contenders able to surmount some of the constraints associated with GIT absorption. Nanoparticles have gained great interest by researchers in recent years as they can be used to improve drug solubility and bioavailability in the harsh GIT environment due to increased surface area to volume ratio, thus provide a rapid onset of therapeutic action [12]. They can also be used to targeting specific sites within the GIT and hence reduce the effects of enzymatic degradation, all of which can improve the safety and effectiveness of drugs [12, 13].

Nanoparticle formulations may be presented in various forms however, polymeric nanoparticles present the versatility of polymers and can be tailored to achieve superior drug stability, enhanced drug payload capacity, longer circulation times and controlled drug release capabilities, when compared with other their colloidal counterparts [14, 15]. In this regard, chitosan-based nanoparticle formulation have been shown to present several of the desirable attributes listed above in addition to being biodegradable, having low toxicity, amenable to tuneable physical properties and bio-adhesive properties [16, 17].

In this chapter we will be discussing the interplay between the GIT physiology/ anatomy and drug physicochemical/biopharmaceutical factors in the absorption process that influence oral therapeutics. We, will also review the physicochemical properties of chitosan relevant for effective GIT delivery, including methods of formulation. The most utilised nanoparticle formulation methods used for chitosan-based nanoparticles are also examined. Finally, we will highlight the recent developments on chitosan-based nanoparticles used in the oral delivery of different drugs.
