Degradable and Injectable Hydrogel for Drug Delivery in Soft Tissues.,Biomacromolecules

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Degradable and Injectable Hydrogel for Drug Delivery in Soft Tissues.
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-11-13 , DOI: 10.1021/acs.biomac.8b01242
Vincent Pertici ₁ , Caroline Pin-Barre ₂ , Claudio Rivera ₃ , Christophe Pellegrino ₃ , Jérôme Laurin ₂ , Didier Gigmes ₁ , Thomas Trimaille ₁

Affiliation

Injectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm- b-PLA- b-PEG- b-PLA- b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel formation at around 30 °C was demonstrated to be mediated by intermicellar bridging through the PEG central block. Such a result was particularly highlighted by the inability of a PEG- b-PLA- b-PNIPAAm triblock analog of the same composition to gelify. The hydrogels degraded through hydrolysis of the PLA esters until complete mass loss due to the diffusion of the recovered PEG and PNIPAAm/micelle based residues in the solution. Interestingly, hydrophobic molecules such as riluzole (neuroprotective drug) or cyanine 5.5 (imaging probe) could be easily loaded in the hydrogels' micelle cores by mixing them with the copolymer solution at room temperature. Drug release was correlated to polymer mass loss. The hydrogel was shown to be cytocompatible (neuronal cells, in vitro) and injectable through a small-gauge needle (in vivo in rats). Thus, this hydrogel platform displays highly attractive features for use in brain/soft tissue engineering as well as in drug delivery.

中文翻译：

可降解和可注射的水凝胶，用于在软组织中输送药物。

可注射水凝胶是组织工程和局部药物输送的有前途的平台，因为它们具有最小的侵入性。我们在这里开发了一种基于两亲性PNIPAAm- b-PLA- b-PEG- b-PLA- b-PNIPAAm五嵌段共聚物的可注射和可生物降解的水凝胶，该共聚物是通过开环聚合/氮氧化物介导的聚合（ROP / NMP）组合而合成的。已证明在30°C左右水凝胶的形成是通过PEG中心嵌段之间的胶束桥接来介导的。通过相同组成的PEG-b-PLA-b-PNIPAAm三嵌段类似物不能胶凝，特别突出了这种结果。由于回收的PEG和PNIPAAm /胶束基残留物在溶液中的扩散，水凝胶会通过PLA酯的水解而降解直至完全质量损失。有趣的是，通过在室温下将其与共聚物溶液混合，可以很容易地将疏水性分子（如利鲁唑（神经保护药）或花菁5.5（成像探针））加载到水凝胶的胶束核心中。药物释放与聚合物质量损失相关。该水凝胶被证明具有细胞相容性（神经细胞，体外），并且可以通过小规格针头注射（在大鼠体内）。因此，该水凝胶平台显示出极富吸引力的功能，可用于脑/软组织工程以及药物输送。体外），并且可以通过小规格针头注射（在大鼠体内）。因此，该水凝胶平台显示出极富吸引力的功能，可用于脑/软组织工程以及药物输送。体外），并且可以通过小规格针头注射（在大鼠体内）。因此，该水凝胶平台显示出极富吸引力的功能，可用于脑/软组织工程以及药物输送。

更新日期：2018-10-30

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