自愈水凝胶
共聚物
单体
基因传递
高分子
聚合物
纳米颗粒
材料科学
化学工程
药物输送
化学
高分子化学
生物物理学
纳米技术
遗传增强
复合材料
基因
生物化学
工程类
生物
作者
Marine Chalanqui,Sreekanth Pentlavalli,Cian M. McCrudden,Phil Chambers,Monika Ziminska,Nicholas Dunne,Helen McCarthy
标识
DOI:10.1016/j.msec.2017.09.003
摘要
Alginate grafted poly(N-isopropylacrylamide) hydrogels (Alg-g-P(NIPAAm)) form three-dimensional networks in mild conditions, making them suitable for incorporation of labile macromolecules, such as DNA. The impact of P(NIPAAm) on copolymer characteristics has been well studied, however the impact of alginate backbone characteristics on copolymer properties has to-date not been investigated. Six different Alg-g-P(NIPAAm) hydrogels were synthesised with 10% alginate, which varied in terms of molecular weight (MW) and mannuronate/guluronate (M/G) monomer ratio, and with 90% NIPAAm in order to develop an injectable and thermo-responsive hydrogel formulation for localised gene delivery. Hydrogel stiffness was directly proportional to MW and the M/G ratio of the alginate backbone. Hydrogels with a high MW or low M/G ratio alginate backbone demonstrated a greater stiffness than those hydrogels comprising low MW alginates and high M/G ratio. Hydrogels with a high M/G ratio also produced a complexed and meshed hydrogel network while hydrogels with a low M/G ratio produced a simplified structure with the superposition of Alg-g-P(NIPAAm) sheets. This study was designed to produce the optimal Alg-g-P(NIPAAm) hydrogel with respect to localised delivery of DNA nanoparticles as a potential medical device for those with castrate resistant prostate cancer (CRPC). Given that CRPC typically disseminates to bone causing pain, morbidity and a plethora of skeletal related events, a copolymer based hydrogel was designed to for long term release of therapeutic DNA nanoparticles. The nanoparticles were comprised of plasmid DNA (pDNA), complexed with an amphipathic cell penetrating peptide termed RALA that is designed to enter cells with high efficiency. Alginate MW and M/G ratio affected stiffness, structure, injectability and degradation of the Alg-g-P(NIPAAm) hydrogel. Algogel 3001, had the optimal characteristics for long-term application and was loaded with RALA/pDNA NPs. From the release profiles, it was evident that RALA protected the pDNA from degradation over a 30-day period and conferred a sustained and controlled release profile from the hydrogels compared to pDNA only. Taken together, we have designed a slowly degrading hydrogel suitable for sustained delivery of nucleic acids when incorporated with the RALA delivery peptide. This now opens up several opportunities for the delivery of therapeutic pDNA from this thermo-responsive hydrogel with numerous medical applications.
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