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Preparation and characterization of stereocomplex aggregates based on PLA–P188–PLA

机译:基于PLA-P188-PLA的立体络合体的制备与表征

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Novel dumbbell-shaped amphiphilic copolymers ((PLLA) _(2) –G1–P188–G1–(PLLA) _(2) and (PDLA) _(2) –G1–P188–G1–(PDLA) _(2) ) and linear-shaped amphiphilic copolymers (PLLA–P188–PLLA and PDLA–P188–PDLA) were synthesized by click chemistry and ring opening polymerization (ROP). The stereocomplexes (scPLA) _(2) –G1–P188–G1–(scPLA) _(2) and scPLA–P188–scPLA were prepared and confirmed by X-ray diffraction (XRD). The stereocomplex interaction between PLLA and PDLA was firstly analyzed using microscale thermophoresis (MST) technology and the dissociation constant ( K _(d) ) was obtained as 342 μM. The aggregation behaviors of these stereocomplexes were studied using fluorescence spectroscopy, transmission electron microscopy (TEM) and light scattering (LS). The critical aggregate concentration (CAC) obtained from fluorescence measurements was 0.021 mg mL ~(?1) for (scPLA) _(2) –G1–P188–G1–(scPLA) _(2) and 0.042 mg mL ~(?1) for scPLA–P188–scPLA. These stereocomplexes can self-associate in aqueous solution into spherical aggregates with a diameter of 181 nm for (scPLA) _(2) –G1–P188–G1–(scPLA) _(2) and 222 nm for scPLA–P188–scPLA. Furthermore, the biocompatibility of the stereocomplexes was evaluated with a relatively lower cytotoxicity. Finally, DOX was encapsulated into the stereocomplex aggregates to evaluate the drug release ability in phosphate buffer at a pH value of 7.4 or 5.4. The drug loading content and the encapsulation efficiency of the aggregates are 9.8%, 54% for (scPLA) _(2) –G1–P188–G1–(scPLA) _(2) and 8.2%, 45% for scPLA–P188–scPLA. The release of DOX at pH 5.4 is faster than that at pH 7.4. The pH value has a greater effect on the release rate of DOX from dumbbell-shaped stereocomplex aggregates than that from the linear-shaped ones, which ensures the long blood circulation and the higher DOX-release surrounding the tumor site.
机译:新型哑铃形两亲性共聚物((PLLA)_(2)-G1-P188-G1-(PLLA)_(2)和(PDLA)_(2)-G1-P188-G1-(PDLA)_(2)通过点击化学和开环聚合(ROP)合成了线性形状两亲共聚物(PLLA-P188-PLLA和PDLA-P188-PDLA)。制备立体复合(SCPLA)_(2)-G1-P188-G1-(SCPLA)_(2)和SCPLA-P188-SCPLA并通过X射线衍射(XRD)证实。首先使用微尺寸热孔(MST)技术(MST)技术分析PLLA和PDLA之间的立体络合相互作用,并获得解离常数(K _(D))为342μm。使用荧光光谱,透射电子显微镜(TEM)和光散射(LS)研究这些立体复合的聚集行为。从荧光测量中获得的临界聚集浓度(CAC)为(SCPLA)_(2)-G1-P188-G1-(SCPLA)_(2)和0.042mg mL〜(α1)的0.021mg )对于scpla-p188-scpla。这些立体复合可以在水溶液中自相关,以直径为181nm的球形聚集体(Scpla)_(2)-G1-P188-G1-(ScPLA)_(2)和222nm用于Scpla-P188-Scpla。此外,通过相对较低的细胞毒性评价立体复合的生物相容性。最后,将DOX包封在立体络合体中,以评估磷酸盐缓冲液的药物释放能力,pH值为7.4或5.4。药物负荷含量和聚集体的封装效率为9.8%,54%(SCPLA)_(2)-G1-P188-G1-(SCPLA)_(2)和8.2%,45%,适用于SCPLA-P188- scpla。 pH 5.4的DOX释放比pH 7.4的释放更快。 pH值对从哑铃形立体络合体的DOX的释放速率产生比来自线性形状的释放速率更大的效果,这确保了肿瘤部位周围的长血液循环和更高的DOX释放。

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