Chauhan Rajat, Kinney Kelsey, Akalkotkar Archana, Nunn Betty M, Keynton Robert S, Soucy Patricia A, O'Toole Martin G
Department of Bioengineering, University of Louisville Louisville KY 40292 USA
RSC Adv. 2020 Apr 23;10(27):16110-16117. doi: 10.1039/d0ra00144a. eCollection 2020 Apr 21.
The probability of human exposure to damaging radiation is increased in activities associated with long-term space flight, medical radiation therapies, and responses to nuclear accidents. However, the development of responsive countermeasures to combat radiation damage to biological tissue is lagging behind rates of human exposure. Herein, we report a radiation-responsive drug delivery system that releases doses of curcumin from a chitosan polymer/film in response to low level gamma radiation exposure. As a fibrous chitosan-curcumin polymer, 1 Gy gamma irradiation (Cs) released 5 ± 1% of conjugated curcumin, while 6 Gy exposure releases 98 ± 1% of conjugated curcumin. The same polymer was formed into a film through solvent casting. The films showed similar, albeit attenuated behavior in water (100% released) and isopropyl alcohol (32% released) with statistically significant drug release following 2 Gy irradiation. ATR FT-IR studies confirmed glycosidic bond cleavage in the chitosan-curcumin polymer in response to gamma radiation exposure. Similar behavior was noted upon exposure of the polymer to 20 cGy (1 GeV amu, at 20 cGy min) high linear energy transfer (LET) Fe radiation based on FTIR studies. Density Functional Theory calculations indicate homolytic bond scission as the primary mechanism for polymer disintegration upon radiation exposure. Films did not change in thickness during the course of radiation exposure. The successful demonstration of radiation-triggered drug release may lead to new classes of radio-protective platforms for developing countermeasures to biological damage from ionizing radiation.
在与长期太空飞行、医学放射治疗以及应对核事故相关的活动中,人类遭受有害辐射的可能性会增加。然而,针对生物组织辐射损伤的响应性对策的开发却落后于人类接触辐射的速度。在此,我们报告了一种辐射响应性药物递送系统,该系统在低水平伽马辐射照射下,从壳聚糖聚合物/薄膜中释放姜黄素剂量。作为一种纤维状壳聚糖 - 姜黄素聚合物,1 Gy伽马辐射(Cs)释放5±1%的共轭姜黄素,而6 Gy照射释放98±1%的共轭姜黄素。通过溶剂浇铸将相同的聚合物制成薄膜。该薄膜在水(100%释放)和异丙醇(32%释放)中表现出类似但减弱的行为,在2 Gy照射后药物释放具有统计学意义。ATR FT - IR研究证实,响应伽马辐射照射,壳聚糖 - 姜黄素聚合物中的糖苷键发生断裂。基于FTIR研究,当聚合物暴露于20 cGy(1 GeV amu,20 cGy/min)高传能线密度(LET)的铁辐射时,也观察到类似行为。密度泛函理论计算表明,均裂键断裂是辐射暴露后聚合物分解的主要机制。在辐射暴露过程中,薄膜厚度没有变化。辐射触发药物释放的成功证明可能会导致新型的辐射防护平台,用于开发针对电离辐射生物损伤的对策。