Drug Des Devel Ther:利福喷丁微球和脂肪干细胞接种在羟基磷灰石/磷酸三钙中制备双重递送抗结核系统

2019-02-04 MedSci MedSci原创

结核(TB)病变中的低药物浓度和清创后的骨缺损或不愈合是治疗骨关节结核病的两个主要问题。因此,药物递送系统和骨组织修复的组合似乎是骨关节结核治疗最有希望的选择。在此,我们报道了一种基于利福喷丁聚乳酸微球(RPMs)治疗感染的新型抗结核双重递送系统,其中添加了脂肪来源的间充质干细胞(ASCs),接种于羟基磷灰石/磷酸三钙(HA/TCP)中促进骨形成。进行细胞增殖,成骨和细胞凋亡以研究利福喷汀对ASC

结核(TB)病变中的低药物浓度和清创后的骨缺损或不愈合是治疗骨关节结核病的两个主要问题。因此,药物递送系统和骨组织修复的组合似乎是骨关节结核治疗最有希望的选择。

在此,我们报道了一种基于利福喷丁聚乳酸微球(RPMs)治疗感染的新型抗结核双重递送系统,其中添加了脂肪来源的间充质干细胞(ASCs),接种于羟基磷灰石/磷酸三钙(HA/TCP)中促进骨形成。进行细胞增殖,成骨和细胞凋亡以研究利福喷汀对ASCs的作用。通过乳液 -溶剂蒸发法合成RPM,然后分别构建单层复合物(ASC + RPM)和三维(3D)复合支架(ASC + RPM + HA/TCP)。碱性磷酸酶(ALP)活性和实时PCR用于确定成骨分化。检测到复合物产生的利福喷汀浓度。

结果表明,当药物浓度低于20μg/mL时,利福喷汀对ASCs增殖和成骨没有影响,显著高于最小抑菌浓度。RPM的载药量和包封率分别为40.56%±2.63%和70.24%±2.18%。单层中细胞的增殖高于3D复合物中的细胞增殖,并且RPM的添加略微增加了细胞增殖。骨复合素和骨桥蛋白的ALP活性和基因表达在3D复合材料中高于单层细胞。通过显微图像和H&E染色观察到良好的生物相容性。释放测试显示,3D复合物显示出利福喷汀的持续释放曲线,持续76天。与单层中的单次递送相比,3D复合物中的双递送系统可以缓和突发释放并延长释放时间的长度。

总之,这种双重递送抗结核支架代表了结核感染和骨缺陷的潜在新策略。

原始出处:

Liang Q, Song X, et al., Development of dual delivery antituberculotic system containing rifapentine microspheres and adipose stem cells seeded in hydroxyapatite/tricalcium phosphate. Drug Des Devel Ther. 2019 Jan 18;13:373-384. doi: 10.2147/DDDT.S190696. eCollection 2019.

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    2019-07-26 wangbingxhy
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    2019-08-08 fzwish20000
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encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1439005, encodeId=c6f7143900543, content=<a href='/topic/show?id=dd2884346fe' target=_blank style='color:#2F92EE;'>#脂肪干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84346, encryptionId=dd2884346fe, topicName=脂肪干细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1509906, encodeId=e27715099062d, content=<a 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564523, encodeId=436c15645239c, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622154, encodeId=4a4f16221545b, content=<a href='/topic/show?id=f41b8000867' target=_blank style='color:#2F92EE;'>#羟基磷灰石#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80008, encryptionId=f41b8000867, topicName=羟基磷灰石)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1801446, encodeId=9d9e18014468b, content=<a href='/topic/show?id=b89ae38472d' target=_blank style='color:#2F92EE;'>#磷酸三钙#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73847, encryptionId=b89ae38472d, topicName=磷酸三钙)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b34252, createdName=chenshujs, createdTime=Fri Jan 10 20:06:00 CST 2020, time=2020-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1862328, encodeId=df99186232827, content=<a href='/topic/show?id=1f0e626267' target=_blank style='color:#2F92EE;'>#Drug#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6262, encryptionId=1f0e626267, topicName=Drug)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=baf586, 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encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1439005, encodeId=c6f7143900543, content=<a href='/topic/show?id=dd2884346fe' target=_blank style='color:#2F92EE;'>#脂肪干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84346, encryptionId=dd2884346fe, topicName=脂肪干细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1509906, encodeId=e27715099062d, content=<a href='/topic/show?id=d9d855612c2' target=_blank style='color:#2F92EE;'>#抗结核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55612, encryptionId=d9d855612c2, topicName=抗结核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c49410165177, createdName=wgx309, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558514, encodeId=03f5155851421, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564523, encodeId=436c15645239c, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622154, encodeId=4a4f16221545b, content=<a href='/topic/show?id=f41b8000867' target=_blank style='color:#2F92EE;'>#羟基磷灰石#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80008, encryptionId=f41b8000867, topicName=羟基磷灰石)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=)]
  6. 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encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1439005, encodeId=c6f7143900543, content=<a href='/topic/show?id=dd2884346fe' target=_blank style='color:#2F92EE;'>#脂肪干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84346, encryptionId=dd2884346fe, topicName=脂肪干细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1509906, encodeId=e27715099062d, content=<a href='/topic/show?id=d9d855612c2' target=_blank style='color:#2F92EE;'>#抗结核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55612, encryptionId=d9d855612c2, topicName=抗结核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c49410165177, createdName=wgx309, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558514, encodeId=03f5155851421, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564523, encodeId=436c15645239c, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622154, encodeId=4a4f16221545b, content=<a href='/topic/show?id=f41b8000867' target=_blank style='color:#2F92EE;'>#羟基磷灰石#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80008, encryptionId=f41b8000867, topicName=羟基磷灰石)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=)]
    2019-02-05 wgx309
  7. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564523, encodeId=436c15645239c, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622154, encodeId=4a4f16221545b, content=<a href='/topic/show?id=f41b8000867' target=_blank style='color:#2F92EE;'>#羟基磷灰石#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80008, encryptionId=f41b8000867, topicName=羟基磷灰石)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=)]
    2019-02-05 fusion
  8. 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href='/topic/show?id=d9d855612c2' target=_blank style='color:#2F92EE;'>#抗结核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55612, encryptionId=d9d855612c2, topicName=抗结核)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c49410165177, createdName=wgx309, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558514, encodeId=03f5155851421, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564523, encodeId=436c15645239c, content=<a href='/topic/show?id=b68a586365' target=_blank style='color:#2F92EE;'>#DES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5863, encryptionId=b68a586365, topicName=DES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=432c14994935, createdName=fusion, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1622154, encodeId=4a4f16221545b, content=<a href='/topic/show?id=f41b8000867' target=_blank style='color:#2F92EE;'>#羟基磷灰石#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80008, encryptionId=f41b8000867, topicName=羟基磷灰石)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Tue Feb 05 16:06:00 CST 2019, time=2019-02-05, status=1, ipAttribution=)]
    2019-02-05 fusion
  9. 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