Cholic Acid-Conjugated Methylcellulose-Polyethylenimine Nano-Aggregates for Drug Delivery Systems

Cholic acid-conjugated methylcellulose-polyethylenimines (MCPEI-CAs) were synthesized and characterized for drug delivery systems. Their synthesis was confirmed by (1)H NMR and FT-IR analysis. Induced circular dichroism result with Congo red showed that methylcellulose (MC) and polyethylenimine-grafted cationic derivative (MC-PEI) would have helical conformation and random coil structure, respectively. It was found that MCPEI-CAs could form positively charged (>30 mV Zeta-potential) and spherical nano-aggregates (~250 nm Z-average size) by hydrophobic interaction of CA moieties. Critical aggregation concentration of MCPEI-CA(10) was measured as 7.2 × 10(−3) mg/mL. MCPEI-CA(10) could encapsulate the anticancer drug doxorubicin (Dox) with 58.0% of drug loading content and 23.2% of drug loading efficiency and its release was facilitated in acidic condition. Cytotoxicity of MCPEI-CAs was increased with the increase of cholic acid (CA) graft degrees, probably due to the cellular membrane disruption by interaction with specific molecular structure of amphiphilic MCPEI-CA nano-aggregates. MCPEI-CA(10)/Dox nano-aggregates showed concentration-dependent anticancer activity, which could overcome the multidrug resistance of cancer cells. In this work, molecular conformation change of MC derivatives by chemical modification and a potential of MCPEI-CA(10)/Dox nano-aggregates for drug delivery systems were revealed.