The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles

Figures & data

Figure 1 The chemical structure of chitin and chitosan.

Figure 2 The synthetized reaction of N-acylated chitosan.

Table 1 The Important Characteristics of Nanoparticle-Based Acylated Chitosan

Acylated Chitosan Nanoparticle	Molecular Weight (MW)/ Deacetylation Degree (DD) / Substitution Degree (SD)	Characteristics of Nanoparticles	Reference
Acylated-Chitosan gold NPs	MW 50–190 kDa DD 70%	The DNA nanoparticle size is 4.659±1.975 nm and the zeta potential is 40.2 mV	[16]
BSA N-acyl modified CSNps	MW 5.23×10^5 DD 84.9% SD 74.4–81.6%	1 mg/mL Bovine Serum Albumin (BSA) nanoparticles size ranges from 138–551 nm and drug loading efficiency ranges from 63.2–81.9%	[17]
Vitamin C N-acyl Chitosan Nanoparticles	MW 5.23×10^5 DD 84.9%	500 mg Vitamin C nanoparticles size ranges from 216–288 nm, zeta potential 5.9±2-8.4 ±2.7 mV, and drug loading efficiency ranges from 55–67%, The drug release is initial burst release (0.5 h): 10–34% (pH 7.4) 20–40% (at pH 1.3) and slowly release over the time	[18]
Thymoquinone N-acyl Chitosan Nanoparticles		The nanoparticle size is 272.6 nm, zeta potential −20.7 /-22.6 mV (before/after lyophilization) mV, and drug loading efficiency is 70.81%,	[19]
Glabirin Chitosan Nanoparticles	DD 74.42% SD 28.02%	1% Glabirin nanoparticles size ranges from 32–42 nm, zeta potential 32.6–34.2 mV	[20]

Figure 3 The synthetized reaction of N-alkylated chitosan.

Table 2 The Important Characteristics of Nanoparticle-Based Alkylated Chitosan

Alkylated Chitosan Nanoparticle	Molecular Weight (MW)/ Deacetylation Degree (DD)/ Substitution Degree (SD)	Characteristics of Nanoparticles	Reference
PNA-Chi Nanoparticles	MW 52 kDa DD 93.5% SD 10.9–15.2%	Poly Nucleic Acid (PNA) nanoparticles size 100 nm, zeta potential 64.2–82.5 mV after 96 hours, and drug loading efficiency 75%,	[29]
Insulin Chitosan Nanoparticles	MW 415,000 g/mol DD 90% SD 10%	Insulin nanoparticles size 120–310 nm, zeta potential 20–32 mV, and drug loading efficiency 11–27% (pH 5.3) and 25–38%, The drug release is 30–70 (first 3–6 h), followed by a slower release for few days	[28]

Figure 4 The synthetized reaction of carboxymethylation chitosan.

Table 3 The Important Characteristics of Nanoparticle-Based Carboxylated Chitosan

Carboxylated Chitosan Nanoparticle	Molecular Weight (MW)/ Deacetylation Degree (DD)/ Substitution Degree (SD)	Characteristics of Nanoparticles	Reference
Carboxymethyl Chitosan-Zno	MW 9 kDa DD 95%	The nanoparticle size is 100 nm	[37]
O-Carboxymethyl Chi/Fucoidan Nanoparticles	MW 192 kDa DD 75% SD 0.315	Curcumin nanoparticles size 269.4 nm, zeta potential 30 mV, and drug loading efficiency 92.8%, The drug release is < 10%/ slow control release (pH 2.5); Sustained release (pH 6) and rapid release (pH 7)	[38]
Carbamazepine- Carboxymethyl Chitosan Nanoparticles	SD 0.384	Carbamazepine nanoparticles size 218.76 nm, zeta potential −33.43 mV, and drug loading efficiency 35.8%, The drug release is >80% after 25 hour	[39]
Doxorubicin Hydrochloride-Loaded O-Carboxymethyl Chitosan	MW Chitosan 10 kDa, Mw CMCS 12 kDa DD 81% SD 92%	Doxorubicin Hydrochloride nanoparticles size 248.9–362.7 nm, zeta potential −27.6 to −42.2 mV and drug loading efficiency 65.48–72.87%, The drug release is after 96 h: 44.9% (pH1.2), 38.36% (pH 6.0) and 79.36% (pH 7.0)	[40]
N-Trimethyl-O-Carboxymethyl Chitosan Nanoparticles	DD 98% SD 36.8%	Heparin nanoparticles size 235 nm, zeta potential 18.6 mV, and drug loading efficiency 76.4%, The drug release is 93.6% ±1.17 after 600 minutes	[41]
Clindamycin HCL-CMCS Nanoparticles	DD 90%	Clindamycin HCL nanoparticles size 318.4 nm and drug loading efficiency 34.68%, The drug release is 94.99% ± 4.70 after 24 h	[42]
HACC-Carboxymethyl Chitosan Nanoparticles	MW 1820 kDa DD 86%	Antigen nanoparticles size 162.40–332.8 nm, zeta potential 19.50–40.60 mV, and drug loading efficiency 48.4–70.%,	[43]

Figure 5 The synthetized reaction of quaternary ammonium chitosan.

Table 4 The Important Characteristics of Nanoparticle-Based Quaternized Chitosan

Quaternized Chitosan Nanoparticle	Molecular Weight (MW)/ Deacetylation Degree (DD)/ Substitution Degree (SD)	Characteristics of Nanoparticles	Reference
TMC/Ɣ-PGA Nanoparticles	MW 60 kDa DD 85% SD 55%	Insulin nanoparticles size 148.6–522.4 nm, zeta potential 14.2–36.6 mV after 96 hours, and drug loading efficiency 73.8%, The drug release is 80% after 700 minutes	[49]
Ribavirin HTCC Nanoparticles	MW 4×10^5 DD 90% SD 0.33–0.83%	Ribavirin nanoparticles size 211 nm, zeta potential 48.6 mV after 96 hours, and drug loading efficiency 10.6%, The drug release is >80% after 70 h (DS 32%)	[50]
Doxycycline Chitosan Nanoparticles		Doxycycline was loaded using quaternary ammonium chitosan. The nanoparticle size is 176 nm, the zeta potential is 12.31 mV, and the drug loading efficiency is 62%,	[52]
Epigallocatechin Gallate-Chi Fucoidan Nanoparticles		Epigallocatechin gallate nanoparticles size 208.5 nm, zeta potential 27.6 mV after 96 hours, and drug loading efficiency 42.%, The drug release is 60% after 360 minutes (pH 2.0) and 80% after 360 minutes (pH 6.8)	[53]

Figure 6 The synthetized reaction of esterification chitosan.

Table 5 The Important Characteristics of Nanoparticle-Based Esterified Chitosan

Esterified Chitosan Nanoparticle	Molecular Weight (MW)/ Deacetylation Degree (DD)/ Substitution Degree (SD)	Characteristics of Nanoparticles	Reference
BSP-Chi Lactate Nanoparticles	MW 190 kDa DD 88% SD 13.2%	Bovine Serum Protein (BSP) nanoparticles size 10 nm and drug loading efficiency 92%, The drug release is 15% over 4 weeks	[59]
Prolidase-Chi Nanoparticles	MW 300 kDa DD 85%	Prolidase nanoparticles size 365.5 nm, zeta potential 17.94 mV, and drug loading efficiency 42.6%, The drug release is 20% after 1 h, massive release after 6–8 h, and sustained release upon 48 h	[61]
Amphotericin B Chitosan Nanoparticles		Amphotericin B nanoparticles size 310 nm, zeta potential −41.5 mV, and drug loading efficiency 89.%, The drug release is sustained release 96% after 72 hour	[62]

Figure 7 The synthetized reaction of etherification chitosan. chitosan (black line) and epoxide (red line.

Table 6 The Important Characteristics of Nanoparticle-Based Etherified Chitosan

Esterified Chitosan NPs	Molecular Weight (MW)/ Deacetylation Degree (DD)/ Substitution Degree (SD)	Characteristics of Nanoparticles	Reference
Cetirizine Chitosan NPs	MW 700 kDa DD 85%	Cetirizine nanoparticles size 129 nm, zeta potential 4 mV, loading efficiency 90%, and drug release is 60–76% in 0–12 h at pH 5.5	[71]

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