**Abbreviations**

**Polymer Drug**

oleoyl-chitosan

254 Advances in Biomaterials Science and Biomedical Applications

**4. Concluding remarks**

**Table 3.** Main characteristics of nanoparticles based on anphiphilic chitosans

Three families of chitosan derivatives have been synthesized and used to prepare nanoparticles for pharmaceutical application, namely, polycations obtained by introducing quaternary ammonium groups on the polymer backbone; thiolated derivatives, and amphiphilic deriva‐ tives obtained by attaching hydrophobic structures to the chitosan or glycol chitosan backbone. The nanoparticles prepared from the quaternary ammonium-chitosan derivatives, especially via the PEC formation method, have shown improved stability and physical properties (smaller size, higher zeta potential) compared to nanoparticles from unmodified chitosan. The thiolated derivatives offered the opportunity to stabilize the nanoparticles by covalent crosslinks formed from interchain thiol oxidation to disulfide, which made the particles stable in the GI environment. The critical aggregation concentration of the amphiphilic hydrophob‐ ically modified chitosan derivatives is usually very low, which implies stability of the self aggregates in dilute conditions, such as those encountered by the nanoparticles in the organ‐ ism. The nanoparticulate systems prepared from chitosan derivatives have generally shown acceptable cytotoxicity. In accord with the known behavior of particles of a size smaller than 500 nm, they have shown endocytic uptake by cells. Smaller particles with higher zeta potential have shown more aptitude to endocytosis. Ionotropically crosslinked TMC nanoparticles are

**Diameter (nm)**

doxorubicin 250-350 not report‐

**Zeta potential (mV)**

**Reference**

ed [43]

BSA Bovine serum albumin CAC Critical aggregation concentration CLSM Confocal laser scanning microscopy CSK CSKSSDYQC peptide DEMC *N*,*N*-diethyl *N*-methyl chitosan DMEC *N*,*N*-dimethyl *N*-ethyl chitosan EPR Enhanced permeability and retention effect FD4 Fluorescein isothiocyanate dextran, molecular weight 4400 Da FITC Fluorescein isothiocyanate GFP Green fluorescent protein GI Gastrointestinal HA Hyaluronic acid

HTCC *N*-(2-hydroxy-3-trimethylammonium) propyl chitosan chloride LLC Lewis lung carcinoma MCC Mono-*N*-carboxymethyl chitosan NAC *N*-acetyl cysteine NALT Nasal associated lymphoid tissue OVA Ovalbumin PEC Polyelectrolyte complex pSEAP Recombinant secreted alkaline phosphatase TBA Thiobutyl amidine TEC *N*-triethyl chitosan TGA Thioglycolic acid TMC N-trimethyl chitosan TPP Sodium tripolyphosphate

### **Author details**

Ylenia Zambito\*

Address all correspondence to: zambito@farm.unipi.it

Dipartimento di Farmacia, Università di Pisa, Italy
