CAJ | 학술논문

背景:含磷脂胆碱的聚乳酸具有优良的生物相容性和降解性能,而且是两性分子.课题前期研究表明用成膜水化法可以自组装成胶束来作为药物载体,但随着疏水链段的增加,成膜水化法很难形成胶束,对于疏水链段较长的磷脂胆碱聚合物能否形成胶束来作为药物载体,目前尚不清楚.目的:采用溶剂挥发法制备磷脂胆碱聚乳酸[phosphorylcholine-containing poly(L-lactide),PLLA-PC]自组装纳米粒子,探讨影响纳米粒子形成和稳定性的因素.方法:①制备PLLA-PC纳米粒子:将PLLA-PC的丙酮溶液滴加到二蒸水中,在室温下磁力搅拌至丙酮挥发完全.F-7000FL220-240V荧光,磷光分光光度计测试胶束溶液的临界胶束浓度,芘为荧光探针,发射波长为395 nm,激发波长为300 nm.JEM-100CX透射电子显微镜观察纳米粒子形态;NANOZSZEN 3600纳米粒度分析仪测其粒径及粒径分布,测试温度为25℃.②凝胶渗透色谱仪GPC测定相对分子质量,色谱仪为Waters 717,流动相为THF,流速1.0 mL/min,聚苯乙烯为标样.每次进样时注入50 μL质量浓度为1 g/L样品溶液.结果与结论:透射电镜显示,PLLA-PC自组装纳米粒子呈壳/核结构.荧光探针检测临界胶束浓度表明,PLLA-PC有很强的表面活性,临界胶束浓度均低于10~(-3)g/L,且随LLA比例变化.动态光散射结果表明,聚合物的亲,疏水链段比例、有机溶剂以及水的用量在纳米粒子形成过程中对粒径有影响,纳米粒子用水稀释时粒径变化不大,且37℃可发生降解.提示溶剂挥发法可以制备粒径可控的PLLA-PC纳米粒子,有望用作新型的纳米药物载体.
배경:함린지담감적취유산구유우량적생물상용성화강해성능,이차시량성분자.과제전기연구표명용성막수화법가이자조장성효속래작위약물재체,단수착소수련단적증가,성막수화법흔난형성효속,대우소수련단교장적린지담감취합물능부형성효속래작위약물재체,목전상불청초.목적:채용용제휘발법제비린지담감취유산[phosphorylcholine-containing poly(L-lactide),PLLA-PC]자조장납미입자,탐토영향납미입자형성화은정성적인소.방법:①제비PLLA-PC납미입자:장PLLA-PC적병동용액적가도이증수중,재실온하자력교반지병동휘발완전.F-7000FL220-240V형광,린광분광광도계측시효속용액적림계효속농도,비위형광탐침,발사파장위395 nm,격발파장위300 nm.JEM-100CX투사전자현미경관찰납미입자형태;NANOZSZEN 3600납미립도분석의측기립경급립경분포,측시온도위25℃.②응효삼투색보의GPC측정상대분자질량,색보의위Waters 717,류동상위THF,류속1.0 mL/min,취분을희위표양.매차진양시주입50 μL질량농도위1 g/L양품용액.결과여결론:투사전경현시,PLLA-PC자조장납미입자정각/핵결구.형광탐침검측림계효속농도표명,PLLA-PC유흔강적표면활성,림계효속농도균저우10~(-3)g/L,차수LLA비례변화.동태광산사결과표명,취합물적친,소수련단비례、유궤용제이급수적용량재납미입자형성과정중대립경유영향,납미입자용수희석시립경변화불대,차37℃가발생강해.제시용제휘발법가이제비립경가공적PLLA-PC납미입자,유망용작신형적납미약물재체.
BACKGROUND: Phosphorylcholine-containing poly (L-lactide) (PLLA-PC) is a kind of novel amphiphilic copolymer with good biocompatibility and biodegradability. In the previous work, self-assembly micelles of PLLA-PC were prepared with film rehydration method. But it hardly formed micelle with film rehydretion method because the longer chains of LLA existed in the PLLA-PC copolymer. However, the mechanism of phosphotipid choline polymer with long hydrophobic chain forming micelle remains still unclear. OBJECTIVE: To prepare self-assembling nanoparticles of PLLA-PC using solvent evaporation method, and to explore the factors that affected the properties and stability of nanoparticles.METHOD: ① Nanoparticles were prepared with solvent evporation metod.PLLA-PC copolymer was dissolved into acetone, and the copolymer solution was added dropwise to distilled water with stirring to yield nanoparticles. The critical micelle concentration (CMC) was performed on the F-7000FL220-240V. The emission and excitation wavelength were 395 nm and 300 mm, respectively. Transmission electron microscopy (TEM) was carried out on a JEM-100CX electron microscope to observe the morphology of PLLA-PC nanoparticles. Dynamic light scattering measurements on nanoparticle solutions were performed on a NANOSIZE 3600 at room temperatire. ②Gel permeation chromatography(GPC)measurements were perfrmed on a Waters 717 apparatus equipped with an RI detector. THF was used as the mobile phase at a flow rate of 1.0 mlJmin. A 1 g/L solution (50 μL) was injected for each analysis. RESULTS AND CONCLUSION: TEM indicated that the PLLA-PC nanoparticles presented typical shell/core structure. The critical micelle concentration was determined by fluorescent probe method. The results showed that the CMCs were quite low ( 10~(-3) g/L) and were dependent on the LLA units in the copolymer. The size and size distribution of the nanoparticles were detected by dynamic light scattering. The results indicated that the size could be affected by the LLA units, concentration of the organic solution and the concentration of the aqueous solution of the nanoparticles. On the other hand, they hardly changed over the dilution with water, which was of great importance in venous injection. They degraded at 37℃. PLLA-PC nanoparticles with controllable sizes can be prepared with phase separation method and might serve as a novel material for drug delivery.