葉酸靶向紫杉醇聚合物納米囊泡的制備及其抗腫瘤活性研究-展示頁
2025-01-24 01:46本頁面
【正文】 ical and chemical properties, in vitro cell cytotoxicity as well as in vivo antitumor activity. METHODS Folatetargeted biodegradable paclitaxelloaded polymersomes posed of PCLbPEGbPCL、mPEG2000DSPE and DSPEPEG(2000) Folate were prepared by thinfilm hydration and ultrasonic method, and characterized in terms of morphology, particle size and size distribution, drug loading content, encapsulation efficiency and in vitro release. The cell cytotoxicity of folatetargeted biodegradable paclitaxelloaded polymersomes in lung carcinoma H1299 cells was observed with CCK8 assay. The in vivo antitumor activity was evaluated in BALB/c mice bearing the EMT6 breast tumor models. RESULTS Folatetargeted biodegradable paclitaxelloaded polymersomes showed spherical coreshell morphology with narrow size distribution. With the increase of drugfed amount, the sizes of folatetargeted biodegradable paclitaxelloaded polymersomes increased, while the drug encapsulating efficiency decreased. The folatetargeted biodegradable paclitaxelloaded polymersomes with drugloading content of 30% were found as spherical shape with the average particle diameter of 311 nm, polydispersity coefficient of and Zeta potential of mV. The folatetargeted biodegradable paclitaxelloaded polymersomes showed a continuous and steady release of PTX without initial burst release. At the paclitaxel concentration of 25181。mL1, the folatetargeted biodegradable paclitaxelloaded polymersomes displayed much less cell cytotoxicity than paclitaxel injections with Cremophor EL. The in vivo tumor inhibiting activity of folatetargeted biodegradable paclitaxelloaded polymersomes was similar to that of paclitaxel injections with Cremophor EL in the same paclitaxel concentration. CONCLUSION The folatetargeted biodegradable paclitaxelloaded polymersomes had high drugloading content and drug encapsulating efficiency, more uniform size and size distribution, excellent drug sustainablerelease behavior, less cytotoxicity, good antitumor activity similar to paclitaxel injections with Cremophor EL. Therefore, folatetargeted biodegradable paclitaxelloaded polymersomes would be a novel paclitaxel preparation in clinic for the treatment of tumor.KEY WORDS: Paclitaxel。 PCLbPEGbPCL。 Cell cytotoxicity。由于PTX在水中溶解度極低，臨床以聚氧乙烯蓖麻油和乙醇溶解后給藥，給藥后存在嚴(yán)重過敏反應(yīng)、腎毒性、神經(jīng)毒性、心臟毒性等不良反應(yīng)，使其臨床應(yīng)用受到限制[3,4]。聚合物囊泡（Polymersome）是由合成或天然改性的雙親性聚合物自組裝構(gòu)成、具有類似脂質(zhì)體雙層結(jié)構(gòu)的封閉空腔球體或類球體。作為藥物載體時(shí),同脂質(zhì)體一樣具有組織相容性和細(xì)胞透過性,但不像脂質(zhì)體容易受氧化或水解,也不易泄漏藥物。近年來，隨著大分子自組裝的飛速發(fā)展，以聚合物囊泡作為一類新型藥物載體的研究得到了廣泛的關(guān)注。因此，將葉酸連接到聚合物囊泡表面，賦予聚合物囊泡對(duì)腫瘤細(xì)胞的主動(dòng)靶向性，可提高藥物在腫瘤組織中的濃度，減輕不良反應(yīng)，實(shí)現(xiàn)腫瘤的靶向治療。1 材料及儀器己內(nèi)酯單體（εCL）（純度99%, 美國Aldrich公司）；聚乙二醇8000（純度99%，美國Sigma公司）；甲氧基聚乙二醇二硬脂酰磷脂酰乙醇胺mPEG2000DSPE（美國Avanti Polar Lipids 公司）；偶聯(lián)葉酸的磷脂DSPEPEG(2000) Folate，（美國Avanti Polar Lipids 公司）；紫杉醇原料藥（純度99%，中國重慶美聯(lián)制藥有限公司）；紫杉醇對(duì)照品（含量測定用，中國生物制品檢定所）；紫杉醇/聚氧乙烯蓖麻油注射劑(6 mg高效液相色譜（美國Waters公司）；VC 501探頭超聲儀（美國Sonics amp。2 方法 PCLbPEGbPCL兩親性三嵌段共聚物的合成 在辛酸亞錫催化下，用聚乙二醇8000引發(fā)ε己內(nèi)酯（εCL）開環(huán)聚合，合成了PCLbPEGbPCL兩親性三嵌段共聚物。
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