Table 2.

Studies over the last ten years about chitosan (CS) uses in drug delivery systems (DDSs).

System	Drug Loaded	Relevant Results	Reference
CS NPs	Tacrine	The particles showed adequate drug-loading capacity and in vitro release studies showed an initial burst release, followed by a continuous and slow release of the drug. Additionally, polysorbate 80 coating of NPs slightly reduced the drug diffusion-controlled release, and followed the Fickian mechanism	Wilson et al., 2010 [259]
CS-cyclodextrin, carboxymethyl-b-cyclodextrin (CM-b-CD) hybrid nanocarrier	Sulindac	The formation of NPs and encapsulation of sulindac was confirmed through DSC and FTIR analysis. Release profiles indicate a continuous release of the drug throughout 24 h. However, the rate of release was faster during the first hours, being about 55–90% of the drug released after 3 h	Ammar et al., 2011 [260]
CS–Alg Polyelectrolyte Complex NPs	Amoxicillin	The release mechanism of Amoxicillin from the CS-ALG PEC NPS was a combination of both diffusion and erosion. The in vitro drug release studies for 6 hrs revealed the PEC system’s gastroprotective nature and diffusion through the swollen polymeric complex as the main drug release mechanism (Higuchi model), which may significantly reduce the chances of incomplete eradication and systemic side effects.	Arora et al., 2011 [261]
CS/NaHCO3 system	Dipyridamole (DP)	The release profiles exhibited a fast release rate on the first day, then a gently stable release in 16 days, followed by an accelerating linear release over 30 days. For the gelling systems of three formulations in this study, the chitosan hydrogel from one with moderate NaHCO3 concentration at 0.10 mol/L had the lowest DP release rate, which was mainly attributed to its stronger gel structure	Liu et al., 2011 [262]
CS Oligosaccharides (COS)-coated NLC (nanostructured lipid carrier)	Flurbiprofen	The particle was coated with the COS polymer surrounding the surface uniformly, which positively charged NLC dispersions, providing a longer retention time by interacting with the negative mucous. It is also noticed the superior mucoadhesive properties of COS-coated NLCs, beneficial to the ocular drug delivery system.	Luo et al., 2011 [263]
CS–carboxymethyl starch (CMS) NPs	5-aminosalicylic acid (5-ASA)	An initial burst release was observed, which can be attributed to the desorption of loosely attached 5-ASA from the matrix polymers’ surface. The greatest release for 5-ASA-loaded CS–CMS NPs occurred in the release media of high ionic strength, and a significantly small portion of 5-ASA was released in water. Additionally, the amount of drug released from NPs decreased on increasing cross-linking time	Saboktakin et al., 2011 [264]
CS enclosed mesoporous silica NPs (MSN)	Ibuprofen (IBU)	In vitro release properties of samples in a pH range from pH 7.4 to 6.8 was observed, and the release of IBU showed sensitivity to the release medium pH value. The great amount of IBU released was achieved in pH 6.8, pH value around some tumor cells and inflammatory tissues	Chen et al., 2012 [265]
Low molecular weight (LMW) CS NPs	Erythrocytes	LMW CS NPs showed good compatibility with erythrocytes and can be easily attached to the erythrocyte membrane’s surface, suggesting a potential vascular drug delivery system. The composite drug delivery system contains no harmful components and is entirely biodegradable.	Fan et al., 2012 [266]
CS-coated mesoporous silica nanospheres	Ibuprofen (IBU)	A pH-responsive release of IBU has been achieved by varying the shell structure of positively charged CS in the designed pH 4.0–7.4 solution. Under basic conditions, CS forms a gel-like structure that is insoluble and prevents IBU release at pH 7.4. When the pH is below its isoelectric point (6.3), the drug has been released due to protonation of the amino group on CS	Popat et al., 2012 [267]
Ellagic acid encapsulated CS NPs (EA@CS-NP)	Ellagic acid (EA)	The drug-encapsulation and loading-efficiency of the NPs were 94 ± 1.03% and 33 ± 2.15%, respectively. The drug is entirely released in a phosphate buffer medium by 48 h at room temperature, indicating a sustained drug release pattern of EA from EA@CS-NP.	Arulmozhi et al., 2013 [268]
Novel CS-Functionalized Spherical Nanosilica Matrix (CTS-SNM)	Carvedilol (CAR)	The release manner showed a pH dependency, and after the burst release of drug adsorbed on the CTS-SNM surface or mixed with the CS shell, the release pattern of CAR from the CAR-CTS-SNM pores took place in pulses with a rise in pH all along the gastrointestinal tract, regulated by the swelling effect of CS under acidic environment and the shrinking effect in a relatively alkaline environment	Sun et al., 2013 [269]
CS/sodium tripolyphosphate (TPP)-hyaluronic acid-based NPs	Ceftazidime (CFT)	In vitro release and permeation studies showed a prolonged drug release profile from the CS/TPP-hyaluronic acid NPs gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines. The formulation was stable, and the drug activity, as shown by microbiological studies	Silva et al., 2017 [270]
CS/montmorillonite films	Ibuprofen (IBU)	Homogeneous systems with good drug dispersion were obtained, and a slower and more controlled release rate of the drug was observed, indicating that the development of this bio-nanocomposite is promising for DDS	Tavares et al., 2017 [235]
CS/hyaluronic acid hydrogel	Vancomycin	Vancomycin-loaded hydrogels were more reliable and elastic, and the gelation time was shortened. Additionally, the delivery of vancomycin was sustainable for 7 d, reducing the abuse of antibiotics, and the releasing rate was dependent on pH levels	Huang et al., 2018 [271]
Alg/CS hydrogel embedded alginate microspheres	Bull Serum Albumin (BSA)	The controlled release of BSA encapsulated within composite hydrogels showed a significantly lower rate when compared with control hydrogel or microspheres alone, what indicates that this hydrogel/microsphere composite system shows excellent potential for a variety of controlled drug delivery applications, especially in protein delivery	Xing et al., 2019 [272]