授課老師：吳文海 學　　生：林姍虹 報告日期： 2010/12/21

奈米磁性粒子的應用：生物醫療感測器、生物分離、熱療、藥物輸送、標靶治療等。

本研究所用的 PLGA合成聚合物比天然聚合物具有高純度和再現性的優勢，且具有生物相容性及良好的生物降解。

磁性聚合物合成的方法有 bottom-up technique 、 top-down technique 等。 奈米顆粒的形成是利用 top-down technique 是由疏水性、

親水性相互作用，以及離子和凡得瓦爾力，而非聚合、交聯反應，

本研究以乳化蒸發法製備奈米粒子包埋磁性物質，並探討不同條件下粒徑之改變，並利用 TGA、 TEM、 DLS分析其性質。

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Oleic acid

Hydrochloric acid

Iron oxide

Potassium Ferrocyanide

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Poly(D,L-lactide-co-glycolide) (PLGA)

Ethyl acetate

Sodium dodecyl sulfate(SDS)

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MAGNETITE

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將 Iron oxide &Potassium Ferrocyanide 加入過量的鹼

利用共沉澱法製造出 MAGNETITE

HYDROPHOBIC MAGNETITE

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15ml 水溶液 ( 20%Oleic acid &10%ammonium hydroxide)

加入 MAGNETITE

攪拌 30min ， 80 (℃ 在油浴中 )

清洗三次

使用氮氣乾燥 2 h ，可得到 MOA

SINGLE EMULSION EVAPORATION WITH HYDROPHOBIC MAGNETITE

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125mg PLGA 溶解於 2.5ml ethyl acetate( 形成油相 )

加入 MOA ，超音波震盪 10 min

注入 SDS 水相溶液 ( 油相跟水相體積百分比 1:4)

冰浴中，放入均質機 2 min ( 轉速 12000rpm)

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使用鼓式蒸發器 7min

使用透析純化法清洗，共洗四次

奈米微粒預凍－ 80 ℃ 、 3h

冷凍乾燥法 48h 、－ 41 ℃

超音波震盪 10min

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Fig. 1. Surface modified magnetite with oleic acid (MOA).(A) Individual MOA nanoparticle size was around 15 nm. (B) The appearance of clustering was observed by TEM, in agreement with the DLS data (mean size of 255±35 nm).

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Fig. 2. TGA data for magnetite and MOA(magnetite plus oleic acid). The initial decrease in weight was due to the presence of water (approximately 2wt% formagnetite and 1.15% for MOA).

油酸改質後的 MOA 重量損失較多

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Fig. 3. Magnetic–polymeric nanoparticles with medium molecular weight PLGA. (A)4% (w/w) MOA theoretical loading.(B)8% (w/w) MOA theoretical loading.The black particles represent MOA entrapped in the PLGA nanoparticle and MOA surrounded by PLGA nanoparticles (all M-P NPs TEM pictures were not mixed with a contrast agent).

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Fig. 4. (A) Magnetic–polymeric nanoparticle with medium molecular weight PLGA (40–75 kDa) and 4% MOA theoretical loading, which shows MOA entrapped in the PLGA matrix. (B) Polymeric nanoparticle with medium PLGA molecular weight (sample was mixed with uracyl acetate at 2% as a contrast agent).

Fig. 5. Effect of SDS concentration on the size and polydispersity index of PLGA nanospheres

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界面活性劑濃度越高粒徑越小，濃度約 5 mg/ml時，粒徑趨於穩定。

Fig. 6. Effect of PLGA concentration and SDS concentration on the nanoparticle size

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界面活性劑濃度較高時，PLGA 粒徑改變不明顯。

Table 1Size of PLGA nanoparticles without magnetite entrapped in the polymeric matrix

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分子量越小，粒徑越小隨分子量改變， PI沒有明顯變化表面帶負電荷可以避免粒子聚集

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Table 2Effect of pre-sonication time of MOA on the PLGA nanoparticles size with magnetite entrapped in the polymeric matrix

MOA pre-sonication refers to sonication of the organic phase formed with PLGA,MOA, and ethyl acetate for 2, respectively, for 10min. Following the emulsification step, the samples were further sonicated for 10min to reduce the emulsion droplet size, n =3.

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Fig. 7. PLGA nanoparticles size and polydispersity measured by DLS (at 25◦C,n = 3).

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Table 3Entrapment of magnetite oleic acid and SDS residue in nanoparticles

n =3.A Theoretical loading: initial amount of MOA added to the nanoparticle formation process (wt%).B Nanosphere yield: final weight of sample after freeze drying (mg)/initial weight of sample (mg).C Entrapment efficiency: MOA in samples (wt%)/theoretical loading (wt%).D SDS residue: total residue (wt%) (from TGA)–magnetite (wt%) (from colorimetric method).E SDS removed: SDS residue (wt%)/total SDS added in the nanoparticle formation process (wt%).

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Fig. 8. SDS profiles acquired by TGA. Temperature was varied from 25 to 600 ◦C. A residue of 24.75% composed of sulfate and sodium group of the SDS molecule was found at 600 ◦C.

利用油酸作表面改質使包埋的 magnetite 成疏水聚合物，具有高包埋率。

提高 MOA 的含量 4%→8% ，粒徑 100nm→120nm 。

PLGA 分子量越高， MOA 包埋率越高。

SDS 濃度可控制奈米粒子的大小，當界面活性劑濃度越高，粒徑越小。

超音波震盪是另一個是影響奈米磁性粒子大小和粒度分佈的重要因素，震盪時間較久的粒徑及分佈都較小。

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Thank you for your attention