- - - Zeta Zeta Zeta % Zeta - doi /cpj t 1 / h h

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1 * 2* Zeta % Zeta Zeta ± 1. 52nm ± 0. 12mV ± 2. 43% ± 0. 13% t 1 / h10. 0 h 74. 0% Zeta - doi /cpj R944 A Preparation and Evaluation of Triptolide-Loaded Chitosan / PEG-PLA Nanoparticles LI Jing 1 ZHOU Ying 1 XU Xiu-ling 2 WANG Hai-nan 1 3* WEI Ying-hui 2* GUO Man-man 2 LI Fan-zhu 2 1. College of Life SciencesGuizhou UniversityGuiyang China2. College of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou China3. China Food and Drug Adminstration Beijing China ABSTRACTOBJECTIVE to evaluate their quality. METHODS To prepare triptolide-loaded chitosan /polyethylene glycol-polylactic acid PEG-PLAnanoparticles and Low molecular weight chitosan was obtained by degradation reactionand the viscosity-average molecular weight and degree of deacetylation were determined by viscometry and acid-base titration methodrespectively. The PEG- PLA nanoparticles were prepared by emulsification solvent evaporation method with chitosan as modifying agent. Then the influence of modification of chitosan on the nanoparticles was investigated. The morphological characteristicsparticle sizezeta potentialencapsulation efficiencydrug loading and release in vitro of the prepared nanoparticles were evaluated. RESULTS The viscosity-average molecular weight and degree of deacetylation of chitosan were and 90% respectively. The particle size and Zeta potential of the nanoparticles increased after the modification of chitosanwhile the encapsulation efficiency was almost the same. The shape of the prepared nanoparticles was sphericaland the mean particle sizezeta potentialencapsulation efficiency and drug loading were ± 1. 52nm ± 0. 12mV ± 2. 43% and ± 0. 13% respectively. The release profiles showed that the accumulated release rate of the nanoparticles was 50. 0% at 1. 1 h and reached 74. 0% at h. CONCLUSION Chitosan modification can affect the particle size and Zeta potential. The nanoparticles show a certain sustained release characteristics with welldistributed particle size as well as high entrapment efficiency. KEY WORDStriptolidechitosanPEG-PLA nanoparticlequality evaluation triptolide TP Tripterygium wilfoidii Hook. F 2 3 Li 3 1 TP R * Tel Fax md_wanghainan@ yahoo. com. cn Tel Fax weiyinghui@ 163. com

2 CS CS chitosan CS 80 ml g % 3 h 5 mol L - 1 ph polyethylene glycol-polylactic acid PEG-PLA g ml 0. 45% PEG-PLA 55 2 h 15 ml 30% % 2 h 5 mol triptolide-loaded chitosan /PEG-PLA nanoparticles L - 1 ph r CS /TP-NPs min Agilent 1200 Agilent CP225D Sartorius JEM- 1200EX Jeol Nano - ZS Mark-Houwink CS M w = % CS η= M η M η = % PEG-PLA M w = PEG Daton M w = degree of deacetylation DD > 98% DD Poloxamer 188 BASF WP- WA544C 1. 2 Malvern HJ - 6B mol L - 1 g 9. 94% HZ S 2. 2 DZG TP PEG-PLA TGL - 16B r min - 1 DL5M 30 g L - 1 poloxamer ⅡDN 2 min360 W 2 s1 s FJ FJ Viskase h 900 bar ATS ATS 10 g L - 1 Labconco Labconco poloxamer mg ml ml L h η dl g - 1 M η DD% = c HClV HCl - c NaOH V NaOH m chitosan 9. 94% 100% c HCl mol L - 1 c NaOH mol L - 1 V HCl ml V NaOH ml ml 1 HCl g m Chitosan CS /TP-NPs 2. 3 CS 2. 1 CS CS CS /TP-NPs

3 TP-NPs Nano-ZS 2. 2 polydispersity PDIZeta Zeta CS /TP-NPs 1 ml r min HPLC Hypersil ODS mm 200 mm 5 μm -43 CS /TP ml min NPs CS /TP-NPs 1 ml 218 nm 20 μl TP μm CS /TP-NPs CS /TP-NPs TP HPLC CS /TP-NPs encapsulation effi TP ciency EE drug loading DL 5. 0 mg 10 ml EE% = W 0 - W 1 /W 0 100% μg ml - 1 TP DL% = W 0 - W 1 /W t 100% ml 10 ml TP-NPs W t CS /TP-NPs μg ml HPLC CS /TP-NPs 4. 0 ml A ρ TP ph 7. 4 PBS 37 ± μg ml r min ml HPLC HPLC 1 d 5 d CS /TP-NPs ml 10 ml 3. 1 CS HPLC CS /TP-NPs 90% h HPLC min μm TP 10 ml W 0 CS /TP-NPs W 1 CS / TP 300 ml 20% CS M η DD HPLC TP CS /TP min NPs 1. 0 ml μg ~ 200 μg ml - 1 ml - 1 TP ml 10 TP A = ρ r = ml TP ~ 200 μg ml μm TP RSD 1. 84% 1. 05% 1. 70% RSD Zeta 1. 67% 1. 51% 2. 69% CS /TP-NPs RSD 1. 93% min TP 2. 0% 2 min RSD 2. 04% JEM EX

4 97. 6% 99. 7% 98. 6% RSD 1. 80% 1. 22% 1. 93% 97% 3. 3 CS CS 1 1 CS TP-NPs Zeta CS /TP-NPs Zeta CS /TP-NPs CS /TP-NPs ± 1. 52nmPDI ± Zeta ± 0. 12mV CS /TP-NPs CS /TP-NPs ± % ± 0. 13% % ph 7. 4 PBS TP t 1 / h 2. 5 h 99. 9% CS /TP-NPs t 1 / h h 74. 0% 4 10 CS CS 1 NPsA TP B CS /TP-NPsC CS Fig. 1 HPLC Chromatograms of blank nanoparticles A TP standard solution B CS /TP-NPs C 1 Tab. 1 TP-NPs CS /TP-NPs. n = 3 x 珋 ± s Characteristics of TP-NPs and CS /TP-NPs. n = 3 珋 x ± s Type of nanoparticles Particle size /nm PDI Encapsulation efficiency /% Zeta potential /mv TP-NPs ± ± ± ± CS /TP-NPs ± ± ± ± Fig. 2 CS /TP-NPs TEM Photograph of CS /TP-NPs Fig. 3 CS /TP-NPs Particle size distribution of CS / TP-NPs

5 4 Fig. 4 珋 x ± s TP CS /TP-NPs. n = 3 x 珋 ± s In vitro release profiles of TP and CS /TP-NPs. n = h 50% 1. 1 ~ h TP 13 REFERENCES CS CS CS CS CS 4. 2 CS TP-NPs 11 CS CS TP-NPs CS CS Drug Target2011 CS 5 HE W KUANG C C CS in vitroj CS CS PEG-PLA J PEG-PLA J SU M XGAO XSONG Met al. Study on influence of glucoside tripterygium total tablets on metabolism in rats by NMR metabonomic technique J. Chin J Chin Mater Med QIANG ZTAO GXUN Set al. Synthesischaracterization and in vitro evaluation of triptolide-lysozyme conjugate for renal targeting delivery of triptolidej. Arch Pharm Res LI NYANG XZHAI Get al. Multifunctional pluronic /poly ethyleniminenanoparticles for anticancer drugj. J Colloid Interface YUAN Z XLI J J ZHU Det al. Enhanced accumulation of low-molecular-weight chitosan in kidneysa study on the influence of N-acetylation of chitosan on the renal targetingj. J ZHANG H et al. Study on effect of molecular parameters of chitosan on properties of chitosan nanoparticles. Chin Pharm J ESSA SRABANEL J MHILDGEN P. Characterization of rhodamine loaded PEG-g-PLA nanoparticles NPs Effect of poly ethylene glycolgrafting densityj. Int J Pharm YUAN Z XGONG TZHANG Z Ret al. Synthesis and characterization of water-soluble chitosan-prednisolone conjugates. Chin Pharm J CHEN L SZHOU WJIANG Y S. Determination the viscosityaverage molecular weight of chitosanj. Chemistry 9 LIN R XJIANG S HZHANG M S. The methods about degree of deacetylation determination of chitosan J. Chemistry ZHAO H X JIN HCAI J Y. Microstructure and micromechanical properties of chitosan films under different drying conditions. Acta Phys Chim Sin CHEN H LLV J LYAN J et al. The study of PLGA nanoparticle surface modified with chitosan as protein drug carriers J. J 13LIU M XDONG JYANG Y Jet al. Preparation and toxicity L-lactic acidnanoparticles J. Ac Func TP Mater PBS of anticancer drugsj 13 TP PBS of triptolide-loaded polyd 20% ph 7. 4 PBS ta Pharm Sin KHIN Y WFENG S S. Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery. Biomaterials