19 19 Vol. 19 No China Journal of Modern Medicine Oct PLGA/nHA * PLGA / S/ O/ W PLGA/ nha- DTX FTIR FTIR PLGA/ nha- DTX

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1 19 19 Vol. 19 No China Journal of Modern Medicine Oct PLGA/nHA * DTX PLGA / nha S/ O/ W PLGA/ nha- DTX FTIR FTIR PLGA/ nha- DTX 3.92%88.7% PLGA- DTX PLGA 30 d PLGA 62.40%72.70% MTT PLGA/ nha PLGA PLGA- DTX PLGA/ nha- DTX ; - ; ; R 943 A Preparation and in vitro release of Docetaxel loaded PLGA/ nha microspheres * LI Xiang 1, WEI Kun 1, LUO Yun 2, GAO Xin 2, ZHAO Na 1, GUO Wusheng 1 (1.College of Materials Science and Engineering, Materials, Ministry of Education, South China University of Technology, Guangzhou ; 2. Department of Urology of Third Affiliated Hospital of Sun Yat-sen University, Guangzhou Guangdong, P.R.China) Abstract: Objectives To prepare docetaxel (DTX) loaded PLGA/nHA microspheres, research the effect of nha on drug loading, encapsulation efficiency, in vitro of composite microspheres and inhibiting the growth of prostate cancers. Method PLGA/nHA-DTX composite microspheres were prepared by a single-emulsion solvent evaporation method (S/O/W), with hydrophobic anticancer docetaxel as model drug. nha and drug-loaded nha were analyzed by TEM and FTIR, and drug loading, encapsulation efficiency, size and in vitro release of microspheres were studied with SEM, laser particle size analyzer and HPLC, etc. Results The results show that nha have a strong adsorption with DTX. Drug loading and encapsulation efficiency of PLGA/nHA-DTX composite microspheres were 3.92% and 88.7%, and have greatly improved compared to neat PLGA-DTX microspheres. After initial burst, composite microspheres released more slowly than neat PLGA microspheres. At the 30d after in vitro release, the cumulative release rate of composite microspheres and neat PLGA microspheres were respectively 62.40% and 72.70%. Cytotoxicity test results showed that PLGA/nHA composite microspheres had better effect than PLGA microspheres and * No 2007AA No 2007AA No [ ] E- mail weikun@scut.edu.cn 2946

2 19 PLGA/nHA DTX to inhibit cancer cell growth. Conclusion Because nha has a strong adsorption with DTX, PLGA/nHA- DTX composite microspheres compared to neat PLGA-DTX microspheres enhance drug loading and encapsulation efficiency, and have better drug delivery effect. The effect of inhibiting the growth of cancers of the composite microspheres is also better. Key words: Docetaxel; PLGA; hydroxyapatite; composite microsphere; drug delivery Taxotere PLGA O/ W 0.9 g PLGA Mw 3 6 [1 2] ml 50 mg Docetaxel %W/V M450 W/O PLA PLGA glycol chitosan 4 h r/min 3 36 h 1 2 d 15 d [3 4] PLGA/ nha S/ O/ W 50 mg Docetaxel 30 ml 0.25 g HA nha 10 min, 24 h 40 DCM [5~8] Docetaxel nha 0.9 g PL- GA 6 ml r/min 1 min S/O 0.4% W/V [9~11] / S/O/W [21] 1.2 PLGA TEM H nha ph FTIR Nexus Nicolet HA PLGA 1.3 PLGA SEM Nova NanoSEM 430 [12] HA PLGA HA FEI [12~20] LA- 950 Hortiba PLGA PLGA/nHA ml 5 ml 2 mmol/l 2947

3 V/V 5min HPLC HPLC LC- 10A Diamonsil C nm 4.6 mm 5μm / =65/ ml/min nm Y X mg/l Y=16.531X r 2 = mg 5 ml ph 7.4 [22] PBS 0.1%W/V /cm O- H 2c 15 ml /cm DTX 80 r/min 10 ml 2c Docetaxel HA 10 ml 709/cm HA DTX HA 1.6 MTT 3 570/cm 630/cm PC- 3 american type culture HA DTX HA [21] collection 37 5% 95% OH- DTX O- H N- H 90% HA DTX EDTA 0.25% cck8 PC cells/ 24 h 200 μl PL- GA/nHA- DTX PLGA- DTX DTX PLGA/nHA 0.4 ng/ml 32.0 ng/ml 96 h PBS 2 100μL 10μLcck8 2 h 450 nm 2 a b c nha nha DTX DTX FTIR OD % =Ac- As /Ac- Ab 3 PLGA 100% As + +cck8+ PLGA 3c d Ac + +cck8 Ab PLGA/nHA +cck8 GraphPad Prism 5.01 IC 50 2 a b nha nha TEM 2a HA /cm PO /cm /cm SEM 2.1 nha nha nha 1 HA 20~ nm PEG 1 PLGA- DTX PLGA/nHA- DTX 37.40μm 53.88μm HA SEM PLGA- DTX PL

4 19 PLGA/nHA GA/nHA- DTX 83.50% % HA μm % % PLGA- DTX PLGA/nHA- DTX PLGA/nHA- DTX PLGA- DTX 2.6 DTX PLGA/nHA PC Docetaxel PL- PLGA- DTX 11.13% GA/nHA- DTX PLGA- DTX DTX PLGA/nHA- DTX 19.67% PC- 3 PLGA- DTX DTX PLGA/HA PLGA/nHA- DTX PLGA/nHA nha 2 PC- 3 PLGA/nHA- DTX PLGA DTX 96 h PLGA- DTX DTX PLGA- DTX IC HA DTX ng/ml ng/ml P > 30 PLGA- DTX 0.05 PLGA/nHA- DTX IC % PLGA/nHA- DTX 62.40% ng/ml ng/ml P <0.05 PLGA- DOC PL- PLGA GA/HA- DOC IC ng/ml a b ng/ml P <0.05 nha PLGA- DTX ng/ml DTX PLGA/nHA- DTX PLGA/nHA PLGA/- DTX DTX PLGA- DTX PLGA/nHA- DTX IC 50 x±s c d 1 DTX P < PLGA- DTX P < h IC 50ng/mL DTX 5.459±1.099 PLGA- DTX 4.994±1.109 PLGA/nHA- DTX 3.686± PLGA- DTX a b PLGA/nHA- DTXc d SEM DTX % MTT PLGA- DTX PLGA/HA- DTX d 3 Docetaxel O/W S/O/W PLGA- DTX PLGA/nHA- DTX PLGA nha PLGA HA DTX H PLGA/nHA- DTX

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