Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.
Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.
复制标题
三维打印技术制备PLLA/INH缓释植入物及体外药物释放特性的实验研究
DOI：
10.1186/1475-925x-13-97
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发表时间：
2014-07-19
影响因子：
3.9
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Wu G;Wu W;Zheng Q;Li J;Zhou J;Hu Z
背景局部缓释植入物在病变处提供了长期稳定的药物释放。本研究的目的是利用三维打印技术(3DP)制备可生物降解的异烟肼/聚乳酸缓释片，并比较3种不同结构的异烟肼缓释片的体外释药特性。方法在三维打印机上制备了3种不同的释药系统(柱状片(CST)、甜甜圈形片(DST)和多层甜甜圈形片(MDST))，并将异烟肼植入体内。采用动态浸泡法研究了三种植入物的释药特性。采用四甲基偶氮唑盐细胞毒性试验和直接接触试验对种植体的生物相容性进行研究。结果片剂中的PLLA粉末通过3DP能很好地结合在一起，且不崩解。电子显微镜观察表明，异烟肼以“巢状”的方式均匀分布在片剂表面，而多层甜甜圈状片的阻挡层表面致密，不含异烟肼。体外释放30d后，3种片剂中异烟肼的浓度均高于有效抑菌浓度(异烟肼：0.025 ~ 0.05μg/ml)。所有片剂均表现出异烟肼的早期突释。从释药后第6天开始，MDST的药物浓度趋于稳定，且波动不大。DST和CST的药物浓度逐渐降低，且DST的浓度下降速度快于CST。四甲基偶氮唑盐细胞毒性试验和直接接触试验表明异烟肼-聚乳酸片剂细胞毒性低，生物相容性好。结论三维打印技术是制作复杂种植体的可靠技术。在3种植入物中，MDST的药物释放模式最稳定。这是一种理想的抗生素给药系统。生物相容性测试表明，异丙基异丙交酯-聚乳酸植入物无细胞毒性。这种多层甜甜圈形片为抗生素的局部应用提供了一种新的持续缓释方法。
BackgroundLocal slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro.MethodsThree different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope.ResultsThe PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility.ConclusionsThree dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic.