Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size.
Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size.
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通过改变纳米凝胶尺寸来调节基于纳米凝胶的原位形成植入物的 HIV 药物释放。
DOI：
10.1039/c8tb01597j
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Town AR
中科院分区：
文献类型：
--
作者：
Town AR
艾滋病毒是一种全球性的公共卫生威胁，需要终生每天口服药物才能有效治疗。这种药物负担往往导致对药物的依从性差。具有可调节的药物释放动力学的可注射原位形成植入物将允许患者用单次不频繁的注射来代替他们的一些日常药丸。在这项工作中，我们研究了聚（N-异丙基丙烯酰胺）（聚NIPAm）纳米凝胶的大小如何影响艾滋病毒药物洛匹那韦从原位形成的植入物的长效释放行为。制备了四种尺寸的聚NIPAm纳米凝胶，其平均直径为65，160，310和450 nm，其特征在于通过动态光散射。这些纳米凝胶都显示出协同的双重刺激响应行为，仅在生理离子强度下加热至31 °C以上时聚集。将纳米凝胶与洛匹那韦的固体药物纳米颗粒（SDNs）混合，并将该浓缩分散体暴露于生理温度和离子强度，导致原位形成纳米复合植入物。制备具有每种纳米凝胶的三种不同负载的SDN（33、50和66%w/w）。然后在体外评估这些纳米复合材料植入物的药物释放行为和稳定性超过360小时。所有样品显示药物释放的单相，并且应用Ritger-Peppas方程表明Fickian扩散。具有最低负载量的SDNs（33%）的纳米复合材料显示出纳米凝胶直径与溶解常数之间的线性关系。这些结果显示了一种有吸引力的方法，用于调整释放洛匹那韦从原位负载植入物与高载药量。
HIV is a global public health threat and requires life-long, daily oral dosing to effectively treat. This pill burden often results in poor adherence to the medications. An injectable in situ forming implant with tuneable drug release kinetics would allow patients to replace some of their daily pills with a single infrequent injection. In this work, we investigate how the size of poly(N-isopropylacrylamide) (polyNIPAm) nanogels influences the long-acting release behaviour of the HIV drug lopinavir from an in situ forming implant. Four sizes of polyNIPAm nanogels were prepared with mean diameters of 65, 160, 310 and 450 nm as characterised by dynamic light scattering. These nanogels all displayed synergistic dual stimuli responsive behaviour by aggregating only upon heating above 31 °C at physiological ionic strength. Mixing the nanogels with solid drug nanoparticles (SDNs) of lopinavir and exposing this concentrated dispersion to physiological temperature and ionic strength resulted in the in situ formation of nanocomposite implants. Three different loadings of the SDNs (33, 50 and 66% w/w) with each of the nanogels were prepared. The drug release behaviour and stability of these nanocomposite implants were then assessed in vitro over 360 hours. All samples displayed a single phase of drug release and application of the Ritger–Peppas equation indicated Fickian diffusion. Nanocomposites with the lowest loading of SDNs (33%) showed a linear relationship between nanogel diameter and the dissolution constant. These results show an attractive method for tuning the release of lopinavir from in situ loading implants with high drug loadings.
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影响因子：
3.4
作者：
Kilicarslan, Muge;Koerber, Martin;Bodmeier, Roland
通讯作者：
Bodmeier, Roland
DOI：
10.1016/j.jconrel.2013.07.021
发表时间：
2013-11-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Amiram M;Luginbuhl KM;Li X;Feinglos MN;Chilkoti A
通讯作者：
Chilkoti A
影响因子：
3.4
作者：
Z. Shao;A. Negi;C. Osuji
通讯作者：
Z. Shao;A. Negi;C. Osuji
影响因子：
16.1
作者：
Owen A;Rannard S
通讯作者：
Rannard S
影响因子：
15
作者：
Ono, Yousuke;Shikata, Toshiyuki
通讯作者：
Shikata, Toshiyuki