Garg Ashish, Rai Gopal, Lodhi Santram, Jain Alok Pal, Yadav Awesh K
Drug Delivery and Nanotechnology Laboratories, Department of Pharmaceutics, Guru Ramdas Khalsa Institute of Science and Technology Pharmacy, Kukrikheda, Barela 482003, Madhya Pradesh, India.
Drug Delivery and Nanotechnology Laboratories, Department of Pharmaceutics, Guru Ramdas Khalsa Institute of Science and Technology Pharmacy, Kukrikheda, Barela 482003, Madhya Pradesh, India.
Int J Biol Macromol. 2016 Jun;87:449-59. doi: 10.1016/j.ijbiomac.2015.11.094. Epub 2016 Mar 5.
Aim of this research was to prepare hyaluronic acid-modified-cellulose acetate phthalate (HAC) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). HAC copolymer was synthesized and confirmed by fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. HAC NPs with 5-FU were prepared using HAC copolymer and compared with 5-FU loaded cellulose acetate phthalate (CAP) NPs. NPs were characterized by atomic force microscopy (AFM), particle size, zeta potential, polydispersity index, entrapment efficiency, in-vitro release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). HAC NPs were found slower release (97.30% in 48h) than (99.25% in 8h) CAP NPs. In cytotoxicity studies, showed great cytotoxic potential of 5-FU loaded HAC NPs in A549, MDA-MD-435 and SK-OV-3 cancer cellline. HAC NPs showing least hemolytic than CAP NPs and 5-FU. Area under curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and time to reach maximum plasma concentration Tmax), were observed 4398.1±7.90μgh/mL, 145.45±2.25μg/L, 45.74±0.25h, 72±0.50h, respectively of HAC NPs and 119.92±1.78μgh/mL, 46.38±3.42μg/L, 1.2±0.25h, 0.5±0.02h were observed in plain 5-FU solution. In conclusion, HAC NPs is effective deliver carrier of 5-FU for lung cancer.
本研究的目的是制备5-氟尿嘧啶（5-FU）的透明质酸修饰邻苯二甲酸醋酸纤维素（HAC）核壳纳米颗粒（NPs）。合成了HAC共聚物，并通过傅里叶变换红外光谱（FTIR）和核磁共振（NMR）光谱进行了确认。使用HAC共聚物制备了负载5-FU的HAC NPs，并与负载5-FU的邻苯二甲酸醋酸纤维素（CAP） NPs进行了比较。通过原子力显微镜（AFM）、粒径、zeta电位、多分散指数、包封率、体外释放、差示扫描量热法（DSC）和X射线衍射（XRD）对NPs进行了表征。发现HAC NPs的释放速度比CAP NPs慢（48小时内释放97.30%）（8小时内释放99.25%）。在细胞毒性研究中，负载5-FU的HAC NPs在A549、MDA-MD-435和SK-OV-3癌细胞系中显示出巨大的细胞毒性潜力。HAC NPs的溶血率比CAP NPs和5-FU低。观察到HAC NPs的曲线下面积（AUC）、最大血浆浓度（Cmax）、平均驻留时间（MRT）和达到最大血浆浓度的时间（Tmax）分别为4398.1±7.90μgh/mL、145.45±2.25μg/L、45.74±0.25h、72±0.50h，而在普通5-FU溶液中观察到的分别为119.92±1.78μgh/mL、46.38±3.42μg/L、1.2±0.25h、0.5±0.02h。总之，HAC NPs是5-FU用于肺癌的有效递送载体。
