Camptothecin-incorporating N-phthaloylchitosan-g-mPEG self-assembly micellar system: effect of degree of deacetylation.
Amphiphilic grafted copolymers, N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (PLC-g-mPEG), were synthesized from chitosan with different degree of deacetylation (DD=80%, 85%, 90% and 95%). Due to their amphiphilic characteristic, these copolymers could form micelle-like nanoparticles. The critical micelle concentration (CMC) of these nanoparticles with different DD in water was similar (28microg/ml). Under transmission electron microscope (TEM), the nanoparticles exhibited a regular spherical shape with core-shell structure. The particle sizes determined by dynamic light scattering were in the range of 100-250nm, and increased as the %DD of chitosan increased. The cytotoxicity of phthaloylchitosans (PLC) and PLC-g-mPEG in Hela cells line were evaluated. The results showed that cytotoxicity of PLC and PLC-g-mPEG increased with increasing %DD of chitosan. The cytotoxicity of PLC-g-mPEG was significantly lower than that of PLC. Camptothecin as a model drug was loaded into the inner core of the micelles by dialysis method. It was found that %DD of chitosan, corresponding to the N-phthaloyl groups in the inner core of the nanoparticle obtained, was a key factor in controlling %yield, stability of the drug-loaded micelles, and drug release behavior. As the %DD increased, the CPT-loaded micelles stability increased. Release of CPT from the micelles was dependent on the %DD and a sustained release was obtained in high %DD.
Opanasopit
Praneet
P
Nanotechnology for Drug/Gene Delivery Systems Group, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand. praneet@email.pharm.su.ac.th
Ngawhirunpat
Tanasait
T
Rojanarata
Theerasak
T
Choochottiros
Chantiga
C
Chirachanchai
Suwabun
S
D000107:Acetylation; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage*; D048271:Chitosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems; D008823:Micelles; D049329:Nanostructures; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; C515873:N-phthaloyl chitosan-graft-poly(ethylene glycol) methyl ether; D011092:Polyethylene Glycols; D048271:Chitosan; D002166:Camptothecin