Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, North Dakota 58108, United States.
Biomacromolecules. 2012 Aug 13;13(8):2537-45. doi: 10.1021/bm3007924. Epub 2012 Jul 13.
Strategically designed amphiphilic invertible polymers (AIPs) are capable of (i) self-assembling into invertible micellar assemblies (IMAs) in response to changes in polarity of environment, polymer concentration, and structure, (ii) accommodating (solubilizing) substances that are otherwise insoluble in water, and (iii) inverting their molecular conformation in response to changes in the polarity of the local environment. The unique ability of AIPs to invert the molecular conformation depending on the polarity of the environment can be a decisive factor in establishing the novel stimuli-responsive mechanism of solubilized drug release that is induced just in response to a change in the polarity of the environment. The IMA capability to solubilize lipophilic drugs and deliver and release the cargo molecules by conformational inversion of polymer macromolecules in response to a change of the polarity of the environment was demonstrated by loading IMA with a phytochemical drug, curcumin. It was demonstrated that four sets of micellar vehicles based on different AIPs were capable of delivering the curcumin from water to an organic medium (1-octanol) by means of unique mechanism: AIP conformational inversion in response to changing polarity from polar to nonpolar. The IMAs are shown to be nontoxic against human cells up to a concentration of 10 mg/L. On the other hand, the curcumin-loaded IMAs are cytotoxic to breast carcinoma cells at this concentration, which confirms the potential of IMA-based vehicles in controlled delivery of poorly water-soluble drug candidates and release by means of this novel stimuli-responsive mechanism.
具有战略设计的两亲性可反转聚合物（AIP）能够 (i) 自组装成可反转胶束组装体（IMA），以响应环境极性、聚合物浓度和结构的变化，(ii) 容纳（溶解）否则在水中不溶的物质，以及 (iii) 响应局部环境极性的变化反转其分子构象。AIP 能够根据环境极性反转分子构象的独特能力，可能是建立新型刺激响应性药物释放机制的决定性因素，这种机制仅响应环境极性的变化即可诱导药物释放。通过将植物化学药物姜黄素载入 IMA，证明了 IMA 溶解疏水性药物并通过聚合物大分子构象反转响应环境极性变化来递送和释放货物分子的能力。结果表明，四组基于不同 AIP 的胶束载体能够通过独特的机制将姜黄素从水中递送到有机介质（1-辛醇）中：AIP 构象响应极性从极性到非极性的变化而反转。证明 IMA 在 10mg/L 的浓度下对人体细胞没有毒性。另一方面，载有姜黄素的 IMA 在该浓度下对乳腺癌细胞具有细胞毒性，这证实了基于 IMA 的载体在通过这种新型刺激响应机制控制递送电荷不足的水溶性药物候选物和释放方面的潜力。
