由幾丁聚醣/奈米金桿複合材料製備光控制藥物釋放載體
學年 103
學期 1
發表日期 2015-01-30
作品名稱 由幾丁聚醣/奈米金桿複合材料製備光控制藥物釋放載體
作品名稱(其他語言) Preparation of optically controlled drug-release nanocarriers made of chitosan/GNR composites
著者 林莉婕; 董崇民
作品所屬單位
出版者
會議名稱 第三十八屆高分子學術研討會
會議地點 國立台灣科技大學, 台北, 台灣
摘要 本研究主要在製備具溫度及pH值雙重敏感性且光可調控的奈米複合載體以作為藥物控制釋放載體,利用近紅外光照射藥物載體,希望藉由奈米金桿光熱轉換的效應使其溫度上升,載體收縮而釋放藥物。此研究是利用丙烯酸(Acrylic acid, AA)與氮-異丙基丙烯醯胺 (N-isopropylamide, NIPAAm)以可逆加成-斷裂鏈轉移聚合(Reversible addition- fragmentation chain transfer polymerization,RAFT)活性自由基聚合方法合成末端帶有酸基和十二烷基三硫代碳酸酯的窄分子量分佈HOOC-PAA-b-PNIPAAm-CTA共聚物,作為環境敏感型高分子主體,並藉由調整高分子的pH值來控制低臨界溫度值(Lower critical solution temperature,LCST),當pH值調整至5.6以上,可以得到LCST接近於人體溫度37 oC。接著利用硼氫化鈉(NaBH4)將末端的三硫代碳酸酯基還原成巰基(-SH),發現水解後巰基含量提升至23.15 μmol/g,轉化率為57.2 %,隨後透過動態光散射及TEM證明高分子具自組裝的能力。接著將環境敏感型高分子於奈米金桿溶液中進行接枝反應以形成HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR複 合材料,其中奈米金桿是利用種晶生成法合成的,長寬分別為35.50(±3.7) nm和8.20(±1.7) nm,長寬比值(aspect rato , AR)為4.30(± 0.9)且形狀均一之奈米金桿(GNR),其表面電漿共振頻率(SPL,max)約在798 nm的近紅外光。實驗發現50 mg高分子與2.07×10-10 M的GNR反應24 h後具良好的穩定性,以動態光散射測量複合材料的 LCST約為37 oC,表示高分子在接枝上GNR後,對LCST值並無影響。最後將HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR溶液加入幾丁聚醣溶液中進行反應形成Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體,動態光散射及TEM探討其微胞型態,並以近紅外光(1000 mW)照射10分鐘後,由於奈米金桿的表面電漿共振效應,溫度可從25 oC上昇至40 oC,將可作為藥物釋放光熱轉換的能量來源,進行藥物釋放。 In this study﹐dual thermo- and pH-responsive and optical-controlled nanocomposites were prepared to serve as potential carriers for controlled delivery of drugs. After exposed to near-infrared (NIR) irradiation, the opto-thermal conversion characteristics of the gold nanorods (GNRs) in the nanocomposites allowed the transformation of light into heat, which triggered shrinkage of the carriers to release drugs. Reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylic acid (AA) and N-isopropylamide (NIPAAm) was used to synthesize HOOC-PAA-b-PNIPAAm-CTA copolymers with acid and dodecyltrithiocarbonate end groups. The HOOC-PAA-b-PNIPAAm-CTA copolymers were environment-responsive and had narrow molecular weight distribution. Adjusting the pH to above 5.6 could bring the lower critical solution temperature (LCST) of the copolymers to around average normal body temperature (37 oC). NaBH4 was then used to reduce the trithiocarbonate group of the copolymers into thiol (-SH) group. After hydrolysis the content of sulphydryl group in the copolymers increased to 23.15 μmol/g with a conversion rate of 57.2 %. Self-assembling properties of the copolymers were observed by dynamics light scattering (DLS) and transmission electron microscopy (TEM). Uniform size of GNRs with a dimension of 35.50(±3.7) nm in length and 8.20(±1.7) nm in width resulting in an aspect rato (AR) of 4.30(± 0.9) and Longitudinal Surface plasmon resonance (SPL,max) at 798 nm were synthesized by seed-mediate growth method. Afterwards the environment responsive copolymers were added to the GNR solution and grafting reaction to synthesize HOOC-PAA-b-PNIPAAm-CTA/GNR and HOOC-PAA-b-PNIPAAm-SH/GNR composites. The HOOC-PAA-b-PNIPAAm-CTA/GNR and HOOC-PAA-b-PNIPAAm-SH/GNR composites prepared by incubating the copolymers (50mg) with GNRs (2.07×10-10 M) for 24 hours were found to have superior stability. DLS analysis showed that the LCST of the composites at around 37 oC, indicating that the grafting process did not affect the LCST. At last the dual-responsive polymer/gold nanorod (DRP/GNR) composite carriers were prepared by adding the HOOC-PAA-b-PNIPAAm-CTA/GNR and HOOC-PAA-b-PNIPAAm-SH/GNR solution into chitosan solution. DLS and TEM were used to investigate the micelle morphology of the DRP/GNR composite carriers. After 10 minutes of 1000 mW NIR irradiation, the temperature of the DRP/GNR solution increased from 25 oC to 40 oC due to the surface plasmon resonance effect of the GNRs, which could work as the energy resource of opto-thermal conversion for the composite carriers to release drugs.
關鍵字 溫度敏感型;酸鹼敏感型;可逆加成-斷裂鏈轉移聚合;奈米金桿;幾丁聚醣;藥物釋放系統;thermal-responsive;pH-responsive;reversible addition-fragmentation chain transfer polymerization;gold nanorod;chitosan;drug delivery system
語言 zh_TW
收錄於
會議性質 國內
校內研討會地點
研討會時間 20150130~20150131
通訊作者 董崇民
國別 TWN
公開徵稿
出版型式
出處 第三十八屆高分子學術研討會論文集
相關連結

機構典藏連結 ( http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/106778 )