Paclitaxel/MPEG-PCL Nanoparticles: Preparation, Characterization and in Vitro Release

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1 215 nm REFERENCES [1] YAO S L, YANG L. The advance in pain management [J]. Cent China Med J( ), 2007, 31(2): [2] FENG Y, ZHANG Y, YANG Y. Influence factors on preparation of citrus volatile oil microcapsules by spray drying technique [J]. Chin Herb Med( ), 2007, 38(10): [3] RATTES A L R, OLIVEIRA W P. Spray drying conditions and encapsulating composition effects on formation and properties of sodium diclofenac micro-particles [J]. Powder Technol, 2007, 171(1): [4] GU Y, FAWCETT J P. Improved HPLC method for the simultaneous determination of tramadol and O-desmethyltramadol in human plasma [J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2005, 821(2): [5] HU K, FU R, XU P Q, et al. Study on pharmacokinetics of astilbin solid dispersion in rat [J]. Chin J Mod Appl Pharm( ), 2013, 30(10): [6] HE L, HAN R W, TANG X F, et al. Preparation of genistein-loaded MePEG-PLGA Nano-micelle and its pharmacokinetics in rats [J]. Chin J Mod Appl Pharm( ), 2012, 29(6): [7] LI W Q. Biopharmaceutics and Pharmacokinetics [M]. Beijing: People s Medical Publishing House, 2003: MPEG- ( ) - (MPEG-PCL) MPEG-PCL MPEG-PCL ( 1 H-NMR) (FTIR) Zeta (ph=7.4) MPEG-PCL MPEG-PCL (102.3±3.5)nm PDI=0.102 (95.6±3.2)% (8.5±0.4)% - R943 B (2014) DOI: /j.cnki.issn Paclitaxel/MPEG-PCL Nanoparticles: Preparation, Characterization and in Vitro Release ZHENG Yi, HUANG Hang, FU Cuixiang(Department of Pharmacy, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou , China) ABSTRACT: OBJECTIVE To develop paclitaxel(ptx)/mpeg-pcl nanoparticles and investigate its in vitro release behavior. METHODS MPEG-PCL block polymer was synthesized by a ring-opeing polymerization method, followed by the characterization with 1 H-NMR and FTIR. The PTX/MPEG-PCL nanoparticles was firstly prepared by a coprecipitation method, and then characterized by a DLS, TEM and etc. In vitro release study of PTX/MPEG-PCL nanoparticles as a function with time was performed in PBS solution (ph=7.4) at 37. RESULTS With the analysis of 1 H-NMR and FTIR spectrum, MPEG-PCL block polymer (molecular weight=4 875) was successfully synthesized. With the observation of TEM, the developed PTX/MPEG-PCL nanoparticles showed almost spherical in shape with uniform mean particle size about (102.3±3.5)nm. Drug loading effciency and drug loading capacity of PTX/MPEG-PCL nanoparticles were (95.6±3.2)% and (8.5±0.4)%, respectively. In vitro release study indicated that PTX was released in a sustained-release manner from MPEG-PCL nanoparticles. CONCLUSION MPEG-PCL nanoparticle as an excellent carrier for PTX exhibits high drug loading effciency, drug loading Tel: (0577) zym9805@163.com Chin J Mod Appl Pharm, 2014 September, Vol.31 No

2 capacity and sustained release progerty. KEY WORDS: MPEG-PCL; nanoparticle; paclitaxel; in vitro release (paclitaxel PTX) [1] [2-3] - (MPEG-PCL) MPEG PCL (FDA) [4-6] MPEG( Sigma-aldrich) (ε-cl Sigma-aldrich) ( ) ( ) RE-52AA ( ) ZS-90 ( ) JEM-200cx ( JEOL) FD-1A-50 ( ) 1.2 MPEG-PCL [7-8] MPEG ε-cl (200 µl) h MPEG-PCL MPEG-PCL MPEG-PCL MPEG-PCL ε-cl MPEG 1.3 MPEG-PCL MPEG-PCL 180 mg 20 mg 5 ml 5 ml µm MPEG-PCL MPEG- PCL 1.4 MPEG-PCL MPEG-PCL 3 0.5% mg 0.2 ml 0.8 ml r min 1 20 min HPLC Dikma C 18 (150 mm 4.6 mm 5 µm) mol L 1 (ph=5.0) 1.0 ml ml 1 20 µl 230 nm = 100% = MPEG-PCL 100% 1.6 MPEG-PCL 2 ml MPEG-PCL h MPEG-PCL 1094 Chin J Mod Appl Pharm, 2014 September, Vol.31 No

3 1.7 MPEG-PCL 0.5 ml MPEG-PCL ( 8 000~14 000) 15 ml (ph=7.4) h 2 ml 0.45 µm HPLC MPEG-PCL MPEG ε-cl 3.64 MPEG CH 2 CH 2 O 3.38 MPEG CH 3 O PCL (CH 2 ) 3 OCCH 2 CH 2 OOC PEG PCL OCH 2 CH 2 [4,9] 1 MPEG-PCL [10] FTIR PCL (1 729 cm 1 ) 2856 cm cm 1 PCL PEG C-H 2 1 H-NMR FTIR MPEG-PCL [11] 2.2 MPEG-PCL MPEG-PCL MPEG-PCL ( )nm PDI= MPEG / MPEG-PCL Zeta 0 mv MPEG-PCL 4 MPEG-PCL TEM PEG TEM [6] 1 MPEG-PCL Fig. 1 1 H-NMR spectrum of MPEG-PCL block polymer 2 MPEG-PCL Fig. 2 FTIR spectrum of MPEG-PCL block polymer 3 MPEG-PCL Fig. 3 Size distribution image of PTX/MPEG-PCL nanoparticles Chin J Mod Appl Pharm, 2014 September, Vol.31 No

4 4 MPEG-PCL Fig. 4 TEM image of PTX/MPEG-PCL nanoparticles µm MPEG-PCL 0.45 µm 0.45 µm MPEG-PCL ( )% ( )% 2.4 MPEG-PCL h MPEG- 24 h MPEG MPEG-PCL MPEG-PCL 5 MPEG-PCL 8 h 35% 96 h 66% 6 MPEG-PCL MPEG-PCL [12] 3 PCL PCL 5 MPEG-PCL Fig. 5 In vitro release profile of PTX from MPEG-PCL nanoparticles [4,10] PCL PCL (PEG) PCL PEG MPEG 2000 PCL 3000 / ( ) / / MPEG-PCL [6,9] [10] PCL 3000 MPEG-PCL MPEG PBS PCL PCL REFERENCES [1] LAI D, HO K C, HAO Y, et al. Taxol resistance in breast 1096 Chin J Mod Appl Pharm, 2014 September, Vol.31 No

5 cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF [J]. Cancer Res, 2011, 71(7): [2] ALI I, RAHIS-UDDIN SALIM K, et al. Advances in nano drugs for cancer chemotherapy [J]. Curr Cancer Drug Targets, 2011, 11(2): [3] CARUTHERS S D, WICKLINE S A, LANZA G M. Nanotechnological applications in medicine [J]. Curr Opin Biotechnol, 2007, 18(1): [4] GOU M, ZHENG X, MEN K, et al. Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles [J]. Pharm Res, 2009, 26(9): [5] HYUN H, KIM Y H, SONG I B, et al. In vitro and in vivo release of albumin using a biodegradable MPEG-PCL diblock copolymer as an in situ gel-forming carrier [J]. Biomacromolecules, 2007, 8(4): [6] LI X, ZHANG Z, LI J, et al. Diclofenac/biodegradable polymer micelles for ocular applications [J]. Nanoscale, 2012, 4(15): [7] MOON S K, KWANG S S, GILSON K, et al. Ring-opening polymerization of ε-aprolactone by poly (ethylene glycol) by an activated monomer mechanism [J]. Macromol Rapid Commun, 2005, 26(8): [8] SOSNIK A, COHN D. Poly (ethylene glycol)-poly (epsiloncaprolactone) block oligomers as injectable materials [J]. Polymer, 2003, 44(23): [9] LIU Y, NGUYEN J, STEELE T, et al. A new synthesis method and degradation of hyper-branched polyethylenimine grafted polycaprolactone block mono-methoxyl poly (ethylene glycol) copolymers (hy-pei-g-pcl-b-mpeg) as potential DNA delivery vectors [J]. Polymer, 2009, 50(16): [10] KANG Y M, LEE S H, LEE J Y, et al. A biodegradable, injectable, gel system based on MPEG-b-(PCL-ran-PLLA) diblock copolymers with an adjustable therapeutic window [J]. Biomaterials, 2010, 31(9): [11] TANAKA K, KANAZAWA T, SHIBATA Y, et al. Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery [J]. Int J Pharm, 2010, 396(1/2): [12] HYUN H, KIM M S, JEONG S C, et al. Preparation of diblock copolymers consisting of methoxy poly (ethylene glycol) and poly (ε-aprolactone)/poly (L-lactide) and their degradation property [J]. Polymer Eng Sci, 2006, 46(9): HPLC * ( ) HPLC Diamonsil C 18 (250 mm 4.6 mm 5 µm) (A)-0.1% (B) min y= x r= ~60.5 µg ml 1 y= x r= ~130 µg ml 1 y= x r= ~19.6 µg ml 1 y= x r= ~15 µg ml 1 y= x r= ~160 µg ml % 100.4% 99.6% 102.1% 102.3% RSD 2.17% 0.74% 2.64% 1.39% 1.93% R B (2014) DOI: /j.cnki.issn Simultaneous Determination of Peoniflorin, Astilbin, Chlorogenic Acid, Rosmarinic Acid and Glycyrrhizic Acid in Shaoling Xiaoyin Tablets by HPLC FENG Limin, ZHAO Ruizhi *, LU Chuanjian(The Second Affialiated Clinical College, Guangzhou University of Chinese Medicine, Guangzhou , China) ABSTRACT: OBJECTIVE To establish an HPLC analytical method for the determination of peoniflorin, astilbin, chlorogenic acid, rosmarinic acid and glycyrrhizic acid in Shaoling Xiaoyin tablets simultaneously. METHODS The (S ) - (2011B ) (YK2013B1N11) Tel: (020) fenglm12@126.com * Tel: (020) @163.com Chin J Mod Appl Pharm, 2014 September, Vol.31 No