**4.3 In vitro drug release from chitosan NP**

*In vitro* drug release studies give us insights on the response of formulated delivery systems to challenges in *in vivo*. The rate and extent of *in vitro* drug release from chitosan-based NP is influenced by a host of factors, notably, shape and size of the of the delivery system, physicochemical properties of the drug and external media [97]. Three primary mechanisms govern the drug release from chitosan NP, which includes desorption (release of drug from surface), diffusion, and erosion/ degradation of the particle matrix [98]. Erosion or degradation of polymers lead to successive physical depletion of the polymer as chains and bonds break [99]. Drug release from the chitosan NP matrix is often pH dependent because of the solubility of chitosan in acidic media [100]. In acidic media, the matrix swells or disentangles

and may act as an effective barrier to drug diffusion. The extent of drug diffusion through this gelled matrix depends on the diffusivity of the drug [99]. In alkaline media, the polymer matrix does not swell and drug release is controlled mainly by passive diffusion into the medium and the polymer plays an insignificant role in the drug release profile. If the drug is weakly bound to the surface of the NP, an initial burst release occurs [97]. In vitro drug release from chitosan NP usually show a two-step pattern with an initial rapid release followed by sustained release [101]. Patel et al. observed that rifampicin- chitosan NP presents a burst effect in the early stages followed by slow sustained drug release in which 90% of rifampicin was released in the range of 28–34 h. A good correlation fit was obtained between the cumulative drug released and square root of time, signifying that the drug release from the NP is diffusion-controlled as described by the Higuchi model. They concluded that rifampicin release from chitosan NP is pH dependent, i.e., faster at a lower pH than around neutral pH [102]. Similarly, Avadi et al. observed that insulin-loaded gum arabic/chitosan NP present a burst effect release in acidic medium, relating it to high solubility of both chitosan and insulin. No burst release was observed at higher pH values of 6.5 and 7.2. They concluded that the release followed a non-Fickian transport, governed by diffusion and/or swelling of the chitosan chains [103]. The performance of chitosan NP in the GIT depends on its response to the external milieu as discussed above. Equally important is how the GIT responds to the presence of NP. The following section describes the consequence of NP deployment in the GIT in the management of selected diseases and expected responses.
