title: Development and evaluation of targeting ligands surface modified paclitaxel nanocrystals.
abstract: To overcome the toxicity of excipient or blank nanoparticles for drug delivery nano-system, the surface modified paclitaxel nanocrystals (PTX-NC) have been developed. PTX-NCs were prepared by nano-precipitation method. The surface of PTX-NCs were modified by grafting with apo-transferrin (Tf) or hyaluronic acid (HA). The physical properties of PTX-NCs were evaluated by field emission scanning electron microscope (FE-SEM), zeta-sizer, zeta-potential, differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectrometry. In vitro drug release study was performed in phosphate buffered saline (PBS) with or without 0.5% (w/v) Tween 80 for 24h. Cellular uptake was studied at time intervals of 0.5, 1, and 2h in MCF-7 cells, and cell growth inhibition study was performed for 24h using MCF-7 cells (cancer cells), and HaCaT cells (normal cells). Three different types of PTX-NCs with a mean size of 236.0±100.6nm (PTX-NC), 302.0±152.0nm (Tf-PTX-NC) and 339±180.6nm (HA-PTX-NC) were successfully prepared. The drug release profiles showed 29.1%/6.9% (PTX (pure)), 40.7%/23.9% (PTX-NC), 50.5%/25.1% (Tf-PTX-NC) and 46.8/24.8% (HA-PTX-NC) in PBS with/without 0.5% (w/v) Tween 80 for 24h, respectively. As per the results, the drug release of PTX-NCs showed the faster release as compared to that of PTX (pure). Surface modified PTX-NCs exhibited higher values for cell permeability than unmodified PTX-NC in the cellular uptake study. Surface modified PTX-NCs inhibited the cell growth approximately to 60% in MCF-7 cells, however effect of surface modified PTX-NCs on normal cell line was lower than the PTX-NC and PTX (pure). In conclusion, biological macromolecules (Tf or HA) surface modified PTX-NC enhanced the cellular uptake and the cell growth inhibition.
authors.affiliation: Division of Undeclared Majors, Chosun University, Gwangju 501-759, South Korea.
authors.forename: Jeong Sun
authors.initials: JS
authors.lastname: Sohn
authors.affiliation: Department of Bioenvironmental & Chemical Engineering, Chosun College of Science & Technology, Gwangju 501-744, South Korea.
authors.forename: Doo-Soo
authors.initials: DS
authors.lastname: Yoon
authors.affiliation: Department of Bioenvironmental & Chemical Engineering, Chosun College of Science & Technology, Gwangju 501-744, South Korea.
authors.forename: Jun Youn
authors.initials: JY
authors.lastname: Sohn
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea. Electronic address: eicosa@cnu.ac.kr.
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Park
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea. Electronic address: c34281@gmail.com.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013696:Temperature
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008024:Ligands; D017239:Paclitaxel
keywords: Cell growth inhibition; Cellular uptake; In vitro drug release; Paclitaxel nanocrystals (PTX-NC); Surface modification