速效、長效及高效遞藥系統(tǒng)研究成果綜述(3)

1、速效、長效及高效遞藥系統(tǒng)研究成果綜述(3)又如熱敏脂質(zhì)體 （thermosensitive liposomes） 主要通過選擇具有合適相變溫度的磷脂使脂質(zhì)體在低于相變溫度時呈現(xiàn)固態(tài)， 包載藥物； 高于相變溫度時呈現(xiàn)液態(tài)或半固態(tài)， 釋放藥物。為了進(jìn)一步提高敏感性，可以采用外部加熱的方式提高腫瘤部位的溫度33.Celsion 公司開發(fā)的多柔比星熱敏脂質(zhì)體 ThermoDox,在 40 時 5 min 內(nèi)即可釋放 60%70%, 而在 37 時 30 min 僅能釋放約 20%34.在體內(nèi)， 靜脈給予5 mg·kg1藥物后， 將腫瘤組織加熱到 42 ， 腫瘤中藥物濃度達(dá)到約 25 ng

2、·mg1, 而普通脂質(zhì)體在腫瘤部位的濃度僅為 78 ng·mg1.經(jīng)過 60 天 ThermoDox治療后， 85%荷鱗狀細(xì)胞癌皮下瘤小鼠的腫瘤完全消失， 而普通脂質(zhì)體僅能延緩腫瘤生長35.在 2015 年的II 期臨床試驗(yàn)中， ThermoDox 聯(lián)合放射熱療 （radiof-requency thermal ablation） 將患者的整體生存期從單獨(dú)進(jìn)行放射熱療的 53.6 個月提高到 79 個月。納米遞藥系統(tǒng)在取得諸多成績的同時， 仍然面臨多種瓶頸問題： 納米材料的安全性。目前僅有少數(shù)材料獲準(zhǔn)注射， 極大限制了納米遞藥系統(tǒng)的產(chǎn)業(yè)化和臨床應(yīng)用， 因此設(shè)計(jì)生物相

3、容性良好、可降解的納米材料成為本領(lǐng)域的重要課題； 靶向遞藥系統(tǒng)的體內(nèi)行為仍然有待探索。靶向遞藥系統(tǒng)的尺度為納米級， 其體內(nèi)吸收、分布轉(zhuǎn)運(yùn)和代謝等過程均具有特殊性。如部分納米材料代謝和排泄很慢， 從而容易發(fā)生蓄積， 產(chǎn)生毒性。只有全面闡釋靶向遞藥系統(tǒng)的體內(nèi)行為才能更好的指導(dǎo)其設(shè)計(jì)； 靶向遞藥系統(tǒng)的規(guī)?；a(chǎn)。許多新型納米遞藥系統(tǒng)的制備流程過于復(fù)雜而難以規(guī)?；a(chǎn)， 因此如何優(yōu)化新型納米遞藥系統(tǒng)的制備流程， 設(shè)計(jì)更精密的工業(yè)化生產(chǎn)設(shè)備， 是納米遞藥系統(tǒng)產(chǎn)業(yè)化必須克服的屏障。4 展望。隨著醫(yī)學(xué)、藥學(xué)和材料學(xué)等發(fā)展， 新型遞藥系統(tǒng)層出不窮， 能夠不斷滿足人們越來越高的用藥需求?？傮w而言， 新型遞藥系統(tǒng)

4、的研究目的均在于不斷提高用藥順應(yīng)性和增效、減毒。但許多新型遞藥系統(tǒng)仍然有待完善， 尤其是制劑輔料的安全性、制劑工藝的可操作性和可控性、制劑應(yīng)用的普適性。目前， 速效遞藥系統(tǒng)、緩控釋遞藥系統(tǒng)已有扎實(shí)的理論基礎(chǔ)， 已經(jīng)進(jìn)入臨床應(yīng)用階段并有較多品種上市， 制劑的難度也較低。但針對重大疾病的響應(yīng)性遞藥系統(tǒng)、生物藥物遞藥系統(tǒng)及靶向遞藥系統(tǒng)仍面臨諸多問題， 需要深入開展應(yīng)用基礎(chǔ)研究并逐步走向臨床應(yīng)用。生物藥物遞藥系統(tǒng)的研究意義重大、涉及面廣， 但目前的研究水平較低， 無法充分滿足臨床需求， 仍然存在巨大的發(fā)展空間。靶向遞藥系統(tǒng)的研究得到廣泛關(guān)注，但仍面臨眾多問題， 尤其是產(chǎn)業(yè)化問題亟待解決。對疾病特征的深

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