Hyaluronic acid coated poly(butyl cyanoacrylate) nanoparticles as anticancer drug carriers.
The hyaluronic acid (HA) coated poly(butyl cyanoacrylate) (PBCA) nanoparticles were synthesized through radical polymerization of butyl cyanoarylate (BCA) initiated by cerium ions in the presence of HA. The chemical coupling between HA and PBCA was demonstrated by FTIR, (1)H NMR and X-ray diffraction. The sizes of the nanoparticles with different HA/BCA ratios were 291-325 nm at cerium concentration of 0.8 mmol/L and HA molecular weight of 18,000 Da. Paclitaxel (PTX), a model anticancer drug, was encapsulated in negatively charged nanoparticles with a maximal encapsulation efficiency of 90%. In vitro release demonstrated that HA modification could effectively reduce the initial burst release in the first 10h and provide a sustained release in the subsequent 188 h. As evidenced by the hemolysis assay and MTT assay, HA coating could significantly reduce the cytotoxicity. Cellular uptake indicated that uptake of HA-PBCA nanoparticles by Sarcoma-180 (S-180) cells was 9.5-fold higher than that of PBCA nanoparticles. PTX-loaded HA-PBCA nanoparticles were more potent in tumor growth suppression than PTX-loaded PBCA nanoparticles or PTX injection following intravenous administration to S-180 tumor bearing mice. Therefore, the HA-PBCA nanoparticles could be an effective and safe vehicle for systemic administration of hydrophobic anticancer drugs.
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
Miao
M
He
Ziming
Z
Zhao
Lichen
L
Yin
Cui
C
Tang
Chunhua
C
Yin
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002563:Cerium / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D004659:Enbucrilate / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008422:Materials Testing; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009566:Nitrates / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010316:Particle Size; D011817:Rabbits; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D004337:Drug Carriers; D009566:Nitrates; C532772:cerium(IV) ammonium nitrate; D002563:Cerium; D006820:Hyaluronic Acid; D004659:Enbucrilate; D017239:Paclitaxel