Development of a thermally responsive nanogel based on chitosan-poly(N-isopropylacrylamide-co-acrylamide) for paclitaxel delivery.
A thermally responsive nanogel was developed through the radical polymerization based on chitosan (CTS) and N-isopropylacrylamide (NIPAAm) with acrylamide (AAm) blended to explore the possibility of increasing the volume phase transition temperature (VPTT). The thermally sensitive features of resultant nanogels were studied by determining variance of transmittance and changeable size. The VPTT of the CTS-poly(NIPAAm-co-AAm5.5) nanogel, coplymerized with 5.5% wt. AAm /wt. NIPAAm, was 38 °C in contrast to 32 °C of the CTS-poly(NIPAAm) polymer and the former was studied thereafter. The critical aggregation concentration of CTS-poly(NIPAAm-co-AAm5.5) nanogels was 1.11 μg/mL, much smaller than CTS-poly(NIPAAm) nanogels (5.00 μg/mL). Paclitaxel (PTX) was encapsulated in CTS-poly(NIPAAm-co-AAm5.5) nanogels with loading efficiency of about 9.06 ± 0.195% (n = 3). Thermally responsive PTX in vitro release fromPTX-loaded nanogels was verified. Coumarin-6-loaded nanogels showed thermally responsive cellular uptake because of electrostatic absorptive endocytosis. Furthermore, the half maximal inhibitory concentration of PTX-loaded nanogels was about 2.025 nmol/L, 10-fold improved relative to PTX solutions against SMMC 7721 cells. In vivo, PTX-loaded nanogels presented remarkably higher antitumor efficacy against human colon carcinoma cells HT-29 xenograft nude mice model after intravenous administration. Accordingly, our results reinforced the potential means of CTS-poly(NIPAAm-co-AAm5.5) nanogels for the combination of thermal therapy and chemotherapy.
College of Chemistry and Chemical Engineering, Guangxi University, Nanning, People's Republic of China. Electronic address: wangyjing@gmail.com.
Yajing
Y
Wang
Department of New Drug Screening, Drug Research Institute, Jiangsu CTTQ Pharmaceutical Company, Nanjing, People's Republic of China.
Hongjiang
H
Xu
Pharmaceutical Research Institute, China Pharmaceutical University, Nanjing, People's Republic of China.
Jiu
J
Wang
Pharmaceutical Research Institute, China Pharmaceutical University, Nanjing, People's Republic of China. Electronic address: geliang1981@hotmail.com.
Liang
L
Ge
Pharmaceutical Research Institute, China Pharmaceutical University, Nanjing, People's Republic of China.
Jiabi
J
Zhu
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004705:Endocytosis; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005782:Gels; D019073:HT29 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D044366:Transition Temperature; D023041:Xenograft Model Antitumor Assays
D000180:Acrylic Resins; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005782:Gels; C000595058:chitosan-poly(N-isopropylacrylamide-co-acrylamide); D048271:Chitosan; D017239:Paclitaxel
cancer; chitosan; hydrogel; polymeric drug carrier; responsive delivery system