Jong-Min Lim1, Truong Cai2, Stefan Mandaric3, Sunandini Chopra3, Hyeonwoo Han4, Seokkyu Jang4, Won Il Choi5, Robert Langer6, Omid C Farokhzad7, Rohit Karnik3. 1. Department of Chemical Engineering, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea. Electronic address: jmlim@sch.ac.kr. 2. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 3. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 4. Department of Chemical Engineering, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea. 5. Center for Convergence Bioceramic Materials, Convergence R&D Division, Korea Institute of Ceramic Engineering and Technology, Cheongju, Chungbuk 28160, Republic of Korea. 6. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 7. Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; King Abdulaziz University, Jeddah 22254, Saudi Arabia.
Abstract
HYPOTHESIS: In conventional 'bulk' nanoprecipitation, the capacity to load hydrophobic drugs into the polymeric nanoparticles (NPs) is limited to about 1%. The size distribution of the resulting NPs becomes polydisperse when higher precursor concentration is used to increase the drug loading. Hence, it should be possible to enhance the hydrophobic drug loading in polymeric NPs while maintaining the uniform NP size distribution by optimizing the nanoprecipitation process and purification process. EXPERIMENTS: Systematic studies were performed to enhance the loading of docetaxel (Dtxl) by using a process of centrifugal spin-down, rapid mixing by turbulence, and addition of co-solvent. The size distributions and Dtxl loading of the NPs were measured using dynamic light scattering and HPLC, respectively. FINDINGS: The centrifugal spin-down process helps to maintain uniform size distribution even at the high precursor concentration. In bulk nanoprecipitation, the resulting NPs achieved Dtxl loading up to 3.2%. By adopting turbulence for rapid mixing, the loading of Dtxl increased to 4.4%. By adding hexane as co-solvent, the loading of Dtxl further increased to 5.5%. Because of the drug loading augmentation, high degree of control, and extremely high production rate, the developed method may be useful for industrial-scale production of personalized nanomedicines by nanoprecipitation.
HYPOTHESIS: In conventional 'bulk' nanoprecipitation, the capacity to load hydrophobic drugs into the polymeric nanoparticles (NPs) is limited to about 1%. The size distribution of the resulting NPs becomes polydisperse when higher precursor concentration is used to increase the drug loading. Hence, it should be possible to enhance the hydrophobic drug loading in polymeric NPs while maintaining the uniform NP size distribution by optimizing the nanoprecipitation process and purification process. EXPERIMENTS: Systematic studies were performed to enhance the loading of docetaxel (Dtxl) by using a process of centrifugal spin-down, rapid mixing by turbulence, and addition of co-solvent. The size distributions and Dtxl loading of the NPs were measured using dynamic light scattering and HPLC, respectively. FINDINGS: The centrifugal spin-down process helps to maintain uniform size distribution even at the high precursor concentration. In bulk nanoprecipitation, the resulting NPs achieved Dtxl loading up to 3.2%. By adopting turbulence for rapid mixing, the loading of Dtxl increased to 4.4%. By adding hexane as co-solvent, the loading of Dtxl further increased to 5.5%. Because of the drug loading augmentation, high degree of control, and extremely high production rate, the developed method may be useful for industrial-scale production of personalized nanomedicines by nanoprecipitation.
Authors: Jianjun Cheng; Benjamin A Teply; Ines Sherifi; Josephine Sung; Gaurav Luther; Frank X Gu; Etgar Levy-Nissenbaum; Aleksandar F Radovic-Moreno; Robert Langer; Omid C Farokhzad Journal: Biomaterials Date: 2006-10-20 Impact factor: 12.479
Authors: Omid C Farokhzad; Sangyong Jon; Ali Khademhosseini; Thanh-Nga T Tran; David A Lavan; Robert Langer Journal: Cancer Res Date: 2004-11-01 Impact factor: 12.701