## 9 Biodegradation of Chitosan  
The study of the metabolic fate of chitosan nanoparticles is an important aspect, as it can modulate the bioavailability of these nanoparticles in the body. Biodegradation is the process of breaking down hydrophilic chitosan polymer into smaller fragments that are suitable for renal clearance. The rate of biodegradation process of chitosan is contingent on the degree of deacetylation in the molecule [82]. Failure in the biodegradation of chitosan nanoparticles can undergo retention in the eye, which can exert toxic effects. Basically, the process of hydrolysis of chitosan involves the action of various enzymes that break glucosamine-N-acetyl-glucosamine, glucosamine-glucose, and N-acetyl-glucosamine-N-acetyl-glucosamine linkages in the structure [83]. In vertebrates, the chitosan polymer is acted upon by various acids present in the stomach and is subjected to chemical degradation. The presence of rich microbial flora and lysoszymes in the colon leads to the further degradation of the chitosan polymer [84]. In glycoside hydrolase, 18 families (GH18) and eight human chitinases have been identified. The enzyme chitinase in microorganisms is involved in the  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Chitosan-Based NPs** & **Drug** & **Route** & **Disease Targeted** & **Reference** \\ \hline Poly (lactic acid)-gratted-chitosan & Ambericin B & Topical & Corneal keratitis & [52] \\ Chitosan/Sodium alginate & 5-Fluorouracil & Topical & Corneal cancer & [55] \\ Chitosan nanoparticle & Cyclosporin A & Topical & Dry eye syndrome & [57] \\ Chitosan/sodium & Cettazidime & & Bacterial conjunctivitis & [59] \\ tripolyphosphate-hyduronic & & & & \\ \hline Hyluronic acid-coated chitosan & Dexamethasone & & & [60] \\ Chitosan nanoparticle & Dexamethasone & & & \\ Chitosan/Sodium deoxycholate & & & & [61] \\ surfactant & Prednisolone & Topical & & [62] \\ Chitosan/chondroitin sulphate & Bromfenac sodium & Topical & & [63] \\ \hline Glycosylated chitosan & Beta-adrenergic & & & [65] \\ SLN-chitosan coating & Methazolam & & & \\ Chitosan nanoparticles & Carteboli & & & [67] \\ PEG-modified chitosan & Quercetin & & & [72] \\ Chitosan nanoparticles coated with & Forskolin & Topical & & [73] \\ poly lactic-op glycosic acid & & & & [74] \\ \hline Sulfolbutyleter-\(\beta\)-cyclodextrin/rin/chitosan & \(\beta\) -cyclodextrin & & & Age-related Macular & [76] \\ \hline Chitosan-N-acetyl-L-cysteine & & & & \\ nanoparticles encapsulated in PLGA & Ranibizumab & Prospective & & [77] \\ microparticle & & & & \\ \hline Chitosan-TPP & Rosmarinic acid & & & [78] \\ Chitosan nanoparticle & Daptomycin & & Bacterial and Fungal & [79] \\ Chitosan/Sodium alginate & Daptomycin & & endophthalmitis & [80] \\ Chitosan conjugated with lecithin & Amphotericin B & Topical & & [81] \\ \hline \hline \end{tabular}
\end{table}
Table 2: Summary of Chitosan-based nanoparticles.  
hydrolysis of the acetyl group in chitin, which is the precursor of chitosan [85]. To promote better formulation characteristics, studies have indicated that N-substitution has a predominant effect on the rate of enzymatic biodegradation. The biodistribution of chitosan nanoparticles is dependent on the molecular weight, as an increase in the molecular weight decreases the plasma concentration and formulation modifications [86]. Various parameters, like type of dosage form, particle size, route of administration, and modifications in the functional groups can alter the biodistribution of chitosan nanoparticles in the body.