Type of nanomaterials | Properties of chitosan | Payload | Assembly mechanism or preparation method | Characterization | Mechanism | Animal model | Oral bioavailability | Refs. |
---|---|---|---|---|---|---|---|---|
mPEG-chitosan-oleic acid micelles | Mw: 112 kDa, DD: 15% | CPT | Self-assembly | Size: 178 nm; PDI: 0.28; Surface charge: + 42.8 mV; EE: 55.5%, LC: 8.3% | Chitosan-mediated mucoadhesive effects | Chemically induced colorectal cancer model | 10% (24 h) | [30] |
Gemcitabine-loaded CSKSSDYQC (CSK)-TMC NPs | Mw: 400 kDa DD: > 90% | Gemcitabine | Self-assembly | Size: 173.6 nm; PDI: 0.2; Surface charge: + 18.5 mV; EE: 66.4%, LC:19.4% | CSK-mediated goblet cells active targeting | 4T1 breast tumor mice model | 60.1% | |
Caseinate/triphenylphosphonium -chitosan/alginate NPs | DD: 95%, Viscosity: 100–200 mPa·s | Caseinate | Polyelectrolyte complexation | Size: 430 nm; EE: 75.3%, LC: 5.2% | Alginate mediated pH responsiveness; triphenylphosphonium-mediated mitochondrial targeting | DSS-induced colon colitis mice model | – | [16] |
Chitosan/ 4-(hydroxymethyl) phenylboronic acid pinacol ester (PAPE)-modified fucoidan NPs | – | Small molecule drugs: Phein | Polyelectrolyte complexation | Size: 233.1 nm; PDI: 0.15; EE: 93.6% | (1) pH-responsiveness (2) Enzymatic degradation of chitosan in colon; (3) PAPE-mediated ROS-responsiveness | DSS-induced colon colitis mice model | – | [237] |
Chitosan/poly-L-glutamic acid NPs | Mw: 150 kDa, DD: 95% | Metformin | Ionotropic gelation | Size: 150 nm; PDI: 0.24; Surface charge: + 27.3 mV | pH-responsiveness | Polycystic kidney disease mice model | – | [33] |
Chitosan-binding peptide (CP)/PEG-DSPE/PLGA NPs | – | Itraconazole | Surface coating | Size: 136 nm; PDI: 0.24; Surface charge: + 21.5 mV | (1) 12-mer peptide (ADGVGDAESRTR)-mediated targeting (2) mucus adhesion and pH-responsiveness | C. neoformans-infected mouse models | – | [29] |
CUR-loaded PVA/ guar gum NPs coated with alginate/chitosan microgels | Mw: 1000 kDa DD: 95% | CUR | Polyelectrolyte interactions | Size: 400 μm; EE: 43.8%; LC: 16.1 | (1) Colon enzymatic degradation (2) pH-responsive swelling of the inner layer | DSS-induced colon colitis mice model | – | [238] |
Vancomycin-loaded chitosan-polyaniline microgels | Mw: 190–310 kDa | Vancomycin | Emulsion method | Size: 243.1 nm; PDI: 0.15; EE: 91.3% | lysozyme-cleavable 1,4-β-glycosidic bonds of chitosan for drug release | – | – | [239] |
Resveratrol-loaded Antheraea pernyi silk fibroin NPs embed in chitosan-alginate hydrogels | – | Resveratrol | Iron crosslinking | EE: 68.2%, LC: 6.2% | (1) pH/ROS/GSH- responsiveness (2) Integrin receptors-targeting in colon | DSS-induced colon colitis mice model | – | [53] |
AC-BSA coated with glycol-chitosan and EGAC (organic–inorganic hybrid nanocomposite) | – | BSA | Sequentially surface coated | size: 325 nm; PDI: 0.35; surface charge: − 33.2 mV; EE: 100%; | Layer-by-layer deposition enhanced stability and intestinal permeation | Normal rat model | – | [240] |
Chitosan/insulin-loaded zein-carboxymethylated short-chain amylose nanocomposites | Mw: 140 kDa, DD: 90% | Insulin | Surface coated with chitosan | Size: 311 nm; PDI: 0.22; Surface charge: + 43.7 mV; EE: 89.0%, LC: 6.8% | Chitosan as a permeation enhancer | Diabetic rat model | 15.1% | [241] |
Insulin/HTCC-chitosan complex coated with thiolated hyaluronic acid (core–shell NPs) | Mw: 50 kDa, DD: 95% | Insulin | Polyelectrolyte complexation (based FNC) | Size: 102 nm; PDI: 0.11; Surface charge: − 26.2 mV EE: 91.0%, LC:38.0% | (1) HTCC-chitosan with enhanced solubility (2) HA-SH enhanced mucus-penetration | Type 1 diabetic rats | 11.3% | [54] |
Alginate/chitosan microparticles | – | AvrA protein | Iron crosslinking (Ca2+) | Size: 281 nm; PDI: 0.32; Surface charge: − 11.6 mV; EE: 89.0%, LC: 6.8% | pH-responsiveness for inflammatory colon-targeting | DSS-induced colitis mice model | 1% | [51] |
Insulin-loaded deoxycholic acid modified chitosan NPs | Mw: 100 kDa, DD: 90% | Insulin | Polyelectrolyte complexation | Size: 226.1 nm; PDI: 0.18; Surface charge: + 14.3 mV; EE: 73.5%, LC: 33% | Deoxycholic acid promoted NPs traverse the intestinal epithelium by exploiting the bile acid pathway | Streptozotocin-induced diabetic rats model | 15.9% | [242] |
Chitosan/TPP/insulin NPs | Mw: 90 kDa, DD: 85% | Insulin | Polyelectrolyte complexation based on FNC | Size: 45 nm; PDI: 0.14; Surface charge: + 9.4 mV; EE: 91.0%, LC:27.5% | The smaller size NPs (45 nm) exhibited better hypoglycemic effects over large size NPs (115 nm) | Streptozotocin-induced diabetic rats model | – | [35] |
Chitosan-g-bPEI/pDNA NPs | Mw: 15 kDa, DD: ~ 85% | Insulin-pDNA | Polyelectrolyte complexation | Size: ~ 160 nm; PDI: 0.32; Surface charge: + 37 mV | (1) PEI (0.8 kDa) conjugation enhanced transfection efficiency and reduce toxicity (2) Prolonged the intestinal retention | STZ‐induced diabetic mice model | – | [243] |
H6P/arginylglycylaspartic acid and mannose-modified chitosan NPs | – | Heat shock protein (H6P) | Polyelectrolyte complexation | Size: ~ 320 nm | M cell targeting (RGD peptide) DC cell targeting | NOD mice | – | [244] |
Fluorocarbon-modified chitosan/ antibodies capsules | – | αPDL1 antibody | Polyelectrolyte complexation | Size: ~ 100 nm Surface charge: + 15 mV | Fluorocarbon chains with hydrophobic and lipophobic behaviors enhance cross-membrane penetration | C57BL/6 mice bearing B16F10 melanoma tumors | 4.7% | |
siRNA/mannose-modified trimethyl chitosan-cysteine/TPP-based NPs | TMC Mw: 200 kDa, DD: 85% | siRNA | Polyelectrolyte complexation | Size: ~ 150 nm; PDI: ~ 0.2; Surface charge: + 18.7 mV | Mannose-mediated targeting (to macrophage) caveolae-mediated endocytosis for robust siRNA delivery | LPS/D-gal induced acute liver injury | – | |
Chitosan coated siRNA-loaded lanthanum phosphate nanoparticles (CS/LaP/siRNA NPs) | – | SiRNA LAP | Polyelectrolyte complexation | Size: 210 nm; Surface charge: + 27.0 mV | Chitosan was used as the outer shell to control the excessive growth of lanthanum phosphate complexes | Colorectal cancer mouse model | – | [251] |
Glycol chitosan–taurocholic acid (GT) coated AuNP–siRNA nanocomplex | Mw: 82 kDa | Akt2-siRNA | Polyelectrolyte complexation | Size: 100 ~ 130 nm Surface charge: + 0.4 mV | (1) GT forms a protected layer (2) Taurocholic acid moiety targeting apical sodium bile acid transporters receptor | Orthotopic colorectal liver metastases mice model | – | [57] |
Oxaliplatin and siRNA/folic acid-conjugated CS NPs embed in chitosan and alginate layer-by-layer (LbL) film | Mw: 100–300 kDa DD: 75–85% | Oxaliplatin and siRNA | Polyelectrolyte complexation | Size: 238 nm; Surface charge: + 27.1 mV; EE: > 90% | Folic acid receptor -mediated tumor targeting delivery | Azoxymethane and DSS-induced colon cancer mice model | – | [252] |
siRNA/mannose-modified TMC/anionic crosslinkers (TPP, ES, and HA) NPs | Mw: 200 kDa, quarternization degree: 30% | siRNA | Ionic gelation | Size: 150–200 nm; PDI: 0.1–0.17; surface Charge: + 18.9 ~ + 37.0 mV | Mannose-mediated macrophage targeting different anionic crosslinkers mediated different cellular unpacking kinetics | Acute hepatic injury mice model | – | [253] |
OPBP-1 loaded TMC hydrogel | – | OPBP-1 | – | Swelling degree of the hydrogel reached 94.3% at 1 h | Protected the payloads from the protease degradation | CT26 tumor mice model | 52.8% | [47] |
Gal-siTNF-PLGA NPs loaded alginate/chitosan hydrogel | Mw: 18 kDa | siTNF | Ionic gelation | – | Alginate/chitosan specific degradation in inflamed colon for release payloads | DSS-induced colitis mice model | – |