本文關(guān)鍵詞：載ADM-PLGA微球的納米羥基磷灰石膠原多孔支架的實(shí)驗(yàn)研究　出處：《南方醫(yī)科大學(xué)》2015年碩士論文　論文類(lèi)型：學(xué)位論文

  更多相關(guān)文章： PLGA 阿霉素 納米羥基磷灰石 骨肉瘤

【摘要】：研究背景：骨肉瘤是人類(lèi)在15-20歲這一時(shí)期內(nèi)多發(fā)的常見(jiàn)惡性腫瘤。骨肉瘤患者在20世紀(jì)70年代之前主要通過(guò)手術(shù)進(jìn)行治療,但是在行手術(shù)切除腫瘤之后患者的生存率不足20%。目前我國(guó)作為世界第一人口大國(guó),因骨腫瘤致死或造成殘疾、功能障礙人數(shù)也逐年增多,位居世界各國(guó)之首。關(guān)于骨腫瘤的手術(shù)治療,其主要問(wèn)題不僅在于手術(shù)切除后常常殘存部分未完全切除的腫瘤組織,這是一個(gè)復(fù)發(fā)的極大隱患,而且還有一個(gè)很大的弊端就是在手術(shù)切除腫瘤病灶的同時(shí)切除了病灶處的負(fù)重骨骼；某些發(fā)生在特定部位的腫瘤,特別是脊柱腫瘤,因?yàn)槠浒l(fā)生部位的特殊造成了其常常難以切除,此外,腫瘤組織的跳躍轉(zhuǎn)移以及在手術(shù)中這些組織與正常組織結(jié)構(gòu)的接觸帶來(lái)的醫(yī)源性播散,這些都有可能引起手術(shù)后腫瘤的局部復(fù)發(fā)。因此,在骨腫瘤切除術(shù)后往往需要進(jìn)行化療,在臨床上目前使用最廣泛的傳統(tǒng)的化療藥物比如阿霉素、順鉑、長(zhǎng)春堿類(lèi)這些藥物不僅具有抗腫瘤活性,也因?yàn)樗鼈兤鹦У姆沁x擇性對(duì)人體內(nèi)的各個(gè)組織和器官帶來(lái)了相應(yīng)的毒副作用,常規(guī)治療劑量即可對(duì)人體產(chǎn)生明顯的骨髓移植、心臟毒性、胃腸道反應(yīng)等毒副作用,這些毒副作用降低了患者的治療的依從性和生活質(zhì)量,容易引起患者對(duì)治療的抗拒,通�；熕幬锞哂袝r(shí)間和劑量的依賴(lài),高藥物濃度,較長(zhǎng)的半衰期常�？梢詭�(lái)更好的抗腫瘤效果,但是劑量的提高和用藥時(shí)間的延長(zhǎng)通常會(huì)帶來(lái)更加嚴(yán)重甚至致命的毒副作用。在漫長(zhǎng)的臨床實(shí)踐中人們渴望獲得一種可以提高局部藥物濃度,延長(zhǎng)藥物作用時(shí)間的新的化療藥物來(lái)減少化療相關(guān)毒副作用,提高化療效率。隨著制藥技術(shù)的進(jìn)步,局部緩釋藥物的概念被提出,其思路是緩釋藥物,延長(zhǎng)藥物作用時(shí)間并且局部靶向給藥,提高藥物的選擇性；而隨著骨組織工程技術(shù)的發(fā)展,將局部緩釋藥物與仿生的人工骨材料相結(jié)合制備成為在局部植入后可以靶向選擇性給藥并且能夠修復(fù)手術(shù)造成的負(fù)重骨骼缺損,這種思路為骨腫瘤患者的康復(fù)帶來(lái)了新的希望。藥物局部緩釋系統(tǒng)在腫瘤的治療方面具有良好的應(yīng)用前景,這種系統(tǒng)是將一系列具有良好生物相容性、可降解性的無(wú)機(jī)或有機(jī)材料與一種或者是幾種傳統(tǒng)的化療藥物相結(jié)合,通過(guò)不同的給藥途徑植入腫瘤切除術(shù)后的原病灶處或者是病灶周?chē)慕M織內(nèi),由此達(dá)到類(lèi)似于靶向給藥的目的。藥物局部緩釋給藥系統(tǒng)對(duì)于局部的殘存的腫瘤細(xì)胞、病灶可以作用較長(zhǎng)的時(shí)間,藥物不需要通過(guò)生物代謝,腫瘤細(xì)胞在一個(gè)較長(zhǎng)的時(shí)間內(nèi)暴露在較高濃度的化療藥物下,顯著提高了化療藥物的治療效率,同時(shí)相對(duì)于傳統(tǒng)給藥途徑來(lái)說(shuō)其避免了長(zhǎng)時(shí)間的全身給藥誘發(fā)的各種毒副反應(yīng)。晚期癌癥患者或是不能耐受傳統(tǒng)化療的患者,藥物緩釋系統(tǒng)植入可以增大給藥劑量,局部釋放的藥物可對(duì)腫瘤長(zhǎng)時(shí)間的直接起效,這對(duì)提高晚期患者的生活質(zhì)量以及延長(zhǎng)壽命也有一定的幫助。但是目前的傳統(tǒng)的藥緩釋系統(tǒng)存在著許多的不足之處：1.緩釋系統(tǒng)生物相容性差,植入后產(chǎn)生明顯的異物排斥反應(yīng)；2.緩釋系統(tǒng)的載藥率、封包率低,復(fù)合困難；3.復(fù)合的藥物劑量偏低,持續(xù)釋放時(shí)間不理想；4.復(fù)合后容易分解,穩(wěn)定性差。隨著21世紀(jì)納米技術(shù)的興起,極大地推動(dòng)各個(gè)交叉學(xué)科的進(jìn)步,納米技術(shù)的引入為局部藥物緩釋系統(tǒng)安全性和有效性的提高起到了明顯的推動(dòng)作用。納米顆粒(nano-particle)有著獨(dú)特的表征和理化性質(zhì),小的尺寸、體積使這類(lèi)微粒更容易穿透細(xì)胞屏障進(jìn)入組織間隙,顯著的提高了被細(xì)胞吞噬的能力,此外納米顆粒還可以增加藥物的穩(wěn)定性和可溶性,同時(shí)在改善腎臟的清除率方面可以起到重要作用。在腫瘤組織中的遲滯效應(yīng)(EPR效應(yīng))的基礎(chǔ)上,納米藥物可以選擇性、特異性的通過(guò)配體誘導(dǎo)的細(xì)胞表面的胞吞作用增加藥物的攝入,在進(jìn)一步提高療效的同時(shí)減少腫瘤的耐藥,通過(guò)減少對(duì)非目標(biāo)部位細(xì)胞組織器官的損傷,來(lái)降低毒性。此外因?yàn)榧{米材料有其獨(dú)特的小尺寸、表面或界面效應(yīng),納米級(jí)別的羥基磷灰石這類(lèi)材料可以有效地誘導(dǎo)骨組織再生和細(xì)胞生長(zhǎng),因此在骨傳導(dǎo)性能上其與傳統(tǒng)的毫米、微米材料相比較具有明顯優(yōu)勢(shì)。局部藥物緩釋理念,隨著骨支架修復(fù)材料、抗腫瘤藥物的發(fā)展,在納米醫(yī)學(xué)的新生土壤之上,有望繼續(xù)發(fā)揮優(yōu)勢(shì),開(kāi)發(fā)出性能更佳的抗腫瘤納米緩釋包囊和支架材料。我們課題組構(gòu)建了載ADM-PLGA微球的納米羥基磷灰石膠原多孔支架(ADM-PLGA-NHAC),并對(duì)其表征和骨修復(fù)能力及抗腫瘤活性進(jìn)行了相關(guān)檢測(cè)。研究目的：通過(guò)制備搭載了阿霉素(ADM)、聚乳酸-羥弳基乙酸共聚物(PLGA)納米緩釋微球的納米羥基磷灰石/膠原多孔支架(ADM-PLGA-NHAC),并進(jìn)行相關(guān)實(shí)驗(yàn)檢測(cè)這種材料的理化性質(zhì)、釋藥特點(diǎn)以及驗(yàn)證其體內(nèi)、體外的抗腫瘤能力和骨修復(fù)能力,為本材料的臨床實(shí)驗(yàn)打下堅(jiān)實(shí)基礎(chǔ),為臨床骨肉瘤的治療提供新的思路。研究方法：1.復(fù)乳-溶劑揮發(fā)法加工阿霉素(ADM)-聚乳酸-羥基乙酸共聚物(PLGA)緩釋微球；納米羥基磷灰石/膠原多孔支架(NHAC)通過(guò)冷凍干燥法以納米羥基磷灰石及膠原為原料進(jìn)行制備,在NHAC的制備過(guò)程中加入ADM-PLGA微球制得載ADM-PLGA納米微球的納米羥基磷灰石／膠原多孔支架(ADM-PLGA-NHAC).制備完成后材料在體外通過(guò)透析袋擴(kuò)散法及制備浸提液進(jìn)行材料的藥物釋放動(dòng)力學(xué)實(shí)驗(yàn)和抗腫瘤實(shí)驗(yàn),再通過(guò)掃描電鏡(SEM)、激光粒徑儀等對(duì)微球和支架的表征進(jìn)行相關(guān)測(cè)試。2.新西蘭大白兔的臨界骨缺損模型選擇來(lái)作為本實(shí)驗(yàn)的動(dòng)物模型,造模完成后的動(dòng)物隨機(jī)分為3組：A組骨缺損不予處理作為空白對(duì)照組；B組骨缺損處以NHAC填塞；C組骨缺損處植入載ADM-PLGA-NHAC。在手術(shù)完成后的第8周及12周處死動(dòng)物,并對(duì)股骨標(biāo)本行X線檢查,所得X線結(jié)果根據(jù)Lane-Sandhu標(biāo)準(zhǔn)對(duì)骨缺損的愈合情況進(jìn)行評(píng)價(jià)；X線檢查完成后對(duì)各組的骨標(biāo)本進(jìn)行Micro-CT掃描,掃描圖像導(dǎo)入電腦進(jìn)行3維重建,之后再將掃描數(shù)據(jù)導(dǎo)入Micro-CT自帶的分析軟件進(jìn)行BMD值分析,對(duì)骨缺損修復(fù)情況進(jìn)行定量的分析；骨標(biāo)本行組織學(xué)檢測(cè)(HE、MASSON染色)及掃描電鏡(SEM)檢測(cè)根據(jù)結(jié)果判斷標(biāo)本的骨修復(fù)情況及材料降解情況。3.將MG63細(xì)胞接種于裸鼠皮下,成瘤后裸鼠皮下腫瘤以尖刀片隨機(jī)植入材料,實(shí)驗(yàn)終止時(shí)處死全部裸鼠,腫瘤剝離、稱(chēng)重并測(cè)量腫瘤長(zhǎng)、寬計(jì)算腫瘤體積。并將腫瘤重量、腫瘤體積進(jìn)行比較；將裸鼠皮下腫瘤按照標(biāo)準(zhǔn)程序制作石蠟切片(厚度4umm),行HE染色觀察腫瘤轉(zhuǎn)移、壞死以及心臟毒性,進(jìn)行腫瘤組織TUNEL檢測(cè)并計(jì)算壞死率。4.所有的統(tǒng)計(jì)分析均由SPSS 13.0軟件完成。具體數(shù)據(jù)均用均值±標(biāo)準(zhǔn)差(X±SD)表示,多組間資料采用單因素方差分析(One-way ANOVA),組間比較采用LSD法(least significant difference),若方差不齊則采用Dunnett's T3法進(jìn)行檢驗(yàn)；P值0.05認(rèn)為差異有統(tǒng)計(jì)學(xué)意義。研究結(jié)果：1.本課題組由乳化揮發(fā)法制得的ADM-PLGA納米微球呈圓球形,平均粒徑約為319.5nm±11.17nm,其載藥率為(6.42+0.28)%。制備的ADM-PLGA-NHAC復(fù)合支架,其孔徑經(jīng)測(cè)試約為100-200um,孔隙率可達(dá)到約(82.3±4.6)%,材料多孔而且空洞的內(nèi)壁十分粗糙,有利于細(xì)胞黏附及營(yíng)養(yǎng)交換。釋藥曲線顯示藥物并未出現(xiàn)明顯的突釋現(xiàn)象,24h內(nèi)藥物釋放率約為17.6%,本材料在28d內(nèi)能持續(xù)緩慢釋放ADM,且釋放濃度比較穩(wěn)定。通過(guò)活-死染色及CCK8法檢測(cè)材料的抗腫瘤效果,結(jié)果顯示ADM-PLGA-NHAC材料的浸提液在體外隨著濃度和時(shí)間的增長(zhǎng)可以明顯抑制MG63細(xì)胞的生長(zhǎng)。2.建立新西蘭兔股骨髁骨缺損模型后植入材料,在手術(shù)后的第8周及12周取材進(jìn)行X線攝片分析、Micro-CT掃描3維重建并進(jìn)行BMD值分析,結(jié)果顯示：空白對(duì)照組骨缺損未愈合而載藥的ADM-PLGA-NHAC支架組與未載藥物的NHAC支架組骨愈合程度無(wú)明顯差異。在石蠟切片組織學(xué)檢測(cè)中顯示A組(空白對(duì)照組)未見(jiàn)明顯新骨形成；B組(NHAC組)可見(jiàn)尚未降解的填充材料與散在其間的大量不規(guī)則的新骨組織,新生骨組織開(kāi)始融合；C組(ADM-PLGA-NHAC組)材料降解程度與B組接近,但不規(guī)則的新骨組織數(shù)量及新生骨組織融合程度差于B組。12周末時(shí)A組在骨缺損邊緣處可見(jiàn)少量不規(guī)則新生骨組織,而B(niǎo)組、C組均可見(jiàn)較多的成熟骨組織和骨類(lèi)似組織融合成片且大量的新生骨質(zhì)與膠原廣泛融合且呈片狀,局部仍可見(jiàn)少量尚未降解的填充材料,兩組均未見(jiàn)明顯炎性細(xì)胞浸潤(rùn)及組織壞死。3.裸鼠處死后以肉眼觀察肺組織有無(wú)轉(zhuǎn)移瘤,對(duì)剝離干凈的腫瘤進(jìn)行稱(chēng)重、測(cè)量體積,分別進(jìn)行HE染色及TUNEL檢測(cè),結(jié)果顯示ADM-PLGA-NHAC組的抑瘤效果最好,各組均肺部無(wú)轉(zhuǎn)移,而在腹腔注射阿霉素組裸鼠出現(xiàn)心臟毒性,而其他各組心臟未見(jiàn)明顯異常。研究結(jié)論：1.我們課題組將納米級(jí)別的化療藥物緩釋囊與納米級(jí)別的羥基磷灰石相結(jié)合,通過(guò)乳化揮發(fā)法、冷凍干燥法研制出了載ADM-PLGA納米囊的納米羥基磷灰石/膠原多孔支架并在體外通過(guò)一系列理化檢測(cè)證明了其具有良好粒徑、孔隙率、載藥率、緩釋性能及抗腫瘤能力；2.通過(guò)建立新西蘭兔股骨髁骨缺損模型并植入我們制備的ADM-PLGA-NHAC材料,在8周后及12周后分別進(jìn)行X線、Micro-CT以及組織學(xué)等檢測(cè),結(jié)果充分證實(shí)了載ADM-PLGA納米囊的納米羥基磷灰石／膠原多孔支架具有良好的骨缺損修復(fù)能力；3.我們建立了裸鼠的異種骨肉瘤模型,皮下腫瘤長(zhǎng)至一定程度后我們通過(guò)將材料植入腫瘤內(nèi)部,通過(guò)進(jìn)行瘤重、腫瘤體積的比較以及腫瘤、心臟的組織學(xué)相關(guān)檢測(cè)分析證明了我們研制的這種材料在裸鼠體內(nèi)具有良好的抗腫瘤效果,并且與傳統(tǒng)化療藥物相比較能夠顯著降低其毒副作用。
[Abstract]:Background: osteosarcoma is the most common malignant tumors in multiple human 15-20 years old in this period. In patients with osteosarcoma before 1970s through surgery, but after undergoing surgical resection of the tumor survival rate is less than 20%. with China as the world's most populous country, due to bone tumor death or disability, the number of dysfunction also increased year by year, ranked first in the world. Surgical treatment of bone tumor, the main problem lies not only in the operation is often part of the remaining complete resection of tumor resection, which is a great risk of a relapse, but there are a lot of malpractice is the surgical removal of the tumor lesions and resection of the lesions the weight of bone; something occurring in specific parts of the tumor, especially spinal tumor, because of its special location caused this is often difficult to resection. Outside, skip metastasis of the tumor tissue and the tissue and normal tissue structure contact in patients with iatrogenic dissemination, these are likely to cause local recurrence after surgery of tumors. Therefore, in the bone after tumor resection often need chemotherapy, in current clinical use of traditional chemotherapy drugs such as the most widely doxorubicin, cisplatin, Changchun alkaloids of these drugs not only have antitumor activity, but also because of various tissues in the human body and organs are non selective has brought the corresponding side effects, the dose can be produced by bone marrow transplantation, obvious to the human body cardiac toxicity, side effects such as gastrointestinal reactions, these poison the side effects were reduced on treatment compliance and quality of life, easy to cause the patient to resist treatment, usually rely on chemotherapy with time and dose, high drug concentration, longer Half life can often lead to better anti-tumor effect, but the prolonged dose increased and medication time often leads to more serious or even fatal side effects. In clinical practice in the long people eager to obtain a high local drug concentration, prolong the drug for new chemotherapy drugs to reduce the time of chemotherapy related toxicity effect of chemotherapy efficiency. With pharmaceutical technology, the concept of local drug delivery is put forward, the idea is to release drug, prolong drug action and local drug target, improve the selection of drugs; and with the development of tissue engineering technology, the local drug delivery and biomimetic artificial bone material combination in the preparation of local implantation can become the selective targeting of drug and surgery to repair the defect caused by the bone weight, this idea for the rehabilitation of patients with bone tumor A new hope. The local drug delivery system has a good application prospect in the treatment of tumors, this system is a series of good biocompatibility, biodegradability of inorganic or organic materials with chemotherapy drugs one or several traditional combination, through different routes of administration into the tumor resection after the original lesions or lesions around the organization, so as to achieve similar to the targeted drug delivery. Local drug sustained-release drug delivery system for residual tumor cells in the local lesions, can be a long time, drugs are not needed by the biological metabolism of tumor cells exposed to higher concentrations of drug in chemotherapy for a long time, significantly improve the efficiency of the treatment of chemotherapy, and compared with the traditional way of administration, avoid all kinds of adverse reactions induced by systemic administration of long time late. Cancer patients or intolerant of conventional chemotherapy, drug delivery system can increase the implantation dose, drug release can be directly effect on the local tumor in long time, it will also be helpful to improve the living quality of patients with advanced and prolong the life. But the traditional drug delivery system deficiencies many of the 1. release system has poor biocompatibility and implantation have obvious reject reaction; 2. delivery system drug loading rate, packet rate is low, the composite difficulty; 3. composite dose is low, sustained release time is not ideal; 4. composite easy decomposition, poor stability. With the development of nanotechnology in twenty-first Century. Greatly promote interdisciplinary progress, introduction of nanotechnology for drug delivery system and the effectiveness and reliability has played a significant role in promoting. Nanoparticles (nano-par Ticle) has a unique characterization and physicochemical properties, small size, the volume of the particles more easily penetrate the cell barrier into the tissue space, improve the ability by phagocytosis, in addition of nano particles can also increase the stability of the drug and at the same time improve the solubility, scavenging rate of kidney can play an important role. The hysteresis effect in tumor tissues (EPR effect) on the basis of nano drugs can selectively, endocytosis specific surface by ligand induced cells increased drug intake, reduce tumor drug resistance at the same time to further improve the efficacy, by reducing cellular non target organs damage. To reduce the toxicity. In addition because the nano materials have the unique small size, surface and interface effect, nano hydroxyapatite level of this kind of material can effectively induce bone tissue regeneration and cell So in the growth, osteoconductive with the traditional millimeter, micron material has obvious advantages compared. Local drug delivery concepts with bone scaffold materials, the development of anticancer drugs, on new soil nano medicine, is expected to continue to take advantage of a better anti-tumor sustained-release capsule and nano stent materials. Our group constructed nano hydroxyapatite collagen porous scaffolds loaded ADM-PLGA microspheres (ADM-PLGA-NHAC), and its characterization and anti tumor activity and bone repair ability were tested. Objective: through preparation with adriamycin (ADM), polylactic acid hydroxy group hydroxyl acetic acid copolymer (PLGA) / nano hydroxyapatite nano microspheres collagen scaffold (ADM-PLGA-NHAC), and the physicochemical properties of this material detection experiments, drug release characteristics and verify the in vivo, in vitro anti tumor The ability of tumor and bone repair capacity, a solid foundation for clinical trials of this material lay, to provide new ideas for clinical treatment of osteosarcoma. Methods: 1. double emulsion solvent evaporation process of adriamycin (ADM) - poly lactic acid glycolic acid (PLGA) microspheres; nano hydroxyapatite / collagen porous support (NHAC) by freeze drying method using nano hydroxyapatite and collagen as raw material for preparation of ADM-PLGA microspheres prepared with nano hydroxyapatite / collagen scaffold loaded ADM-PLGA nanoparticles in the preparation of NHAC (ADM-PLGA-NHAC). After preparation, in vitro drug materials by dialysis bag diffusion method and preparation of leaching material extract release kinetics experiment and anti tumor experiment, through scanning electron microscopy (SEM), critical bone characterization of laser particle size analyzer of microspheres and stent related test.2. New Zealand white rabbits. Loss model selection as the experimental animal model, animal model after completion of the randomly divided into 3 groups: group A bone defect not treated as blank control group; group B bone defect by NHAC tamponade; group C bone defect in ADM-PLGA-NHAC. implantation after surgery for eighth weeks and 12 weeks of dead animal, and X-ray examination of femur specimens, the X-ray results were evaluated according to Lane-Sandhu standard of bone defect healing; X-ray examination after the completion of each bone specimens were scanned with Micro-CT and scanned images into a computer for 3 dimensional reconstruction, then scan the data analysis software to import Micro-CT own BMD value analysis, quantitative analysis of bone defect repair; the detection of bone specimens (HE, tissue MASSON staining) and scanning electron microscope (SEM) detection according to the results of judgment and bone degradation.3. samples will be fine MG63 Cells were inoculated in nude mice subcutaneous tumor formation after subcutaneous tumors were implanted into the material with a sharp blade at the end of the experiment, all the mice were sacrificed and tumor, weighing and measuring the tumor length, width and calculate the tumor volume. The tumor weight and tumor volume were compared; the subcutaneous tumor in accordance with standard procedures of paraffin sections (thickness 4umm), observation of tumor metastasis by HE staining, necrosis and cardiac toxicity, tumor tissue TUNEL detection and statistical analysis of computing the necrosis rate of all.4. was completed by SPSS 13 software. The specific data are mean standard deviation (X + SD) said that the data among the groups using ANOVA (One-way, ANOVA) comparison between groups using the method of LSD (least significant difference), if the homogeneity of variance using Dunnett's T3 test; P value of 0.05 is considered statistically significant. Results: 1. the research group by emulsion solvent evaporation method ADM-PLGA nano microspheres are spherical, the average particle size is about 319.5nm + 11.17nm, the drug loading rate (6.42+0.28) ADM-PLGA-NHAC composite scaffolds prepared by%. After testing, the pore diameter is about 100-200um, the porosity can reach about (82.3 + 4.6)%, and the inner wall of the hollow porous material is very rough, there are celladhesion and nutrient exchange. The release curve showed that the drug did not appear obvious burst release phenomenon, 24h in the drug release rate is about 17.6%, the material in 28d during a sustained release of ADM, and the release concentration is relatively stable. Through the live - dead staining and CCK8 assay material anti-tumor effect, results showed that the leaching of growth.2. extract in vitro with the concentration and time of growth can significantly inhibit MG63 cells to establish rabbit bone defect model after implantation of ADM-PLGA-NHAC material, material for X-ray radiography in postoperative eighth weeks and 12 weeks Analysis of Micro-CT scan 3 dimensional reconstruction and BMD analysis results show that: the blank control group ADM-PLGA-NHAC stent group bone defect healing and drug loaded with NHAC stent group without drug loaded bone healing without obvious difference. In the study group A detection of paraffin tissue (blank control group) was no significant new bone formation; B group (group NHAC) and the filling material not visible degradation during the scattered in a large number of irregular new bone tissue, bone fusion; C group (group ADM-PLGA-NHAC) material degradation degree was close to B, but the number of irregular new bone tissue and bone fusion was worse than B group.12 group A at the weekend in the bone at the edge of a small amount of irregular new bone tissue, while in B group, C group showed more mature bone tissue and bone tissue and bone fusion were similar with a large number of collagen fusion and is in a sheet shape, local still A small amount of no degradation of filling materials, the two groups were no obvious inflammatory cell infiltration and tissue necrosis after.3. mice were sacrificed by visual observation of lung tissue without metastasis of the tumors were stripped clean, weighing, measurement of volume, respectively. HE staining and TUNEL detection, the results showed the best antitumor effect of ADM-PLGA-NHAC group, each group all lung metastasis, and after intraperitoneal injection of adriamycin group nude mice heart toxicity, heart and other groups had no obvious abnormalities. Conclusion: 1. our research group will nanoscale drug delivery capsule and chemotherapy combined with other nano hydroxyapatite, by emulsion solvent evaporation method, freeze-drying method developed nano hydroxyapatite / nano ADM-PLGA sac collagen porous scaffolds in vitro and through a series of physical and chemical testing proves that it has good porosity, particle size, drug loading, release property and anti tumor 2. ability; through the establishment of New Zealand rabbit femoral condyle bone defect model and we implanted ADM-PLGA-NHAC materials prepared respectively, X-ray in 8 weeks and 12 weeks after Micro-CT, and histological examination. The results proved that the nano hydroxyapatite / collagen scaffold loaded ADM-PLGA nanoparticles has the ability to repair bone defects is good; 3. we established a xenograft model of osteosarcoma in nude mice subcutaneous tumor, to a certain degree by our internal materials were implanted into the tumor, the tumor weight, tumor volume and tumor, cardiac histological correlation analysis proved that we developed this

【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R738.1

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相關(guān)期刊論文 前1條

1 周雅軒;;納米載藥系統(tǒng)在醫(yī)藥領(lǐng)域中的應(yīng)用進(jìn)展[J];天津藥學(xué);2012年01期

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本文編號(hào)：1377891