Alfano Sara, Ceparano Lorenzo, Brugnoli Benedetta, Forcina Gianluca, Pellegrino Luca, Lauta Francesca Cecilia, Rusconi Roberto, Francolini Iolanda, Piozzi Antonella, Martinelli Andrea
Department of Chemistry, Sapienza University of Rome, P.le A. Moro 5, Rome 00185, Italy.
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele 20072, Italy.
ACS Appl Bio Mater. 2025 Jul 21;8(7):6109-6120. doi: 10.1021/acsabm.5c00676. Epub 2025 Jun 19.
Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters with promising drug delivery applications. Their hydrophobicity enables lipophilic drug encapsulation, enhancing bioavailability but limiting colloidal stability and physiological compatibility. Surfactants crucially improve the nanoparticle dimensional stability, dispersion, wettability of hydrophobic matrices, and cellular interaction, yet conventional surfactants require additional purification and may pose physiological risks. Self-surfactant systems offer a sustainable alternative. Therefore, this research proposes a green chemical modification of PHAs to develop self-surfactant systems. Hydrophilic groups were introduced onto a poly-3-hydroxybutyrate--3-hydroxyhexanoate (PHBHHx) backbone via amidation using choline taurinate ([Ch][Tau]), a biocompatible ionic liquid. This approach eliminates the need for toxic reagents and complex purification. By precisely controlling the PHBHHx/[Ch][Tau] molar ratio, amphiphilic structures with varying hydrophobic tail lengths were produced, as confirmed by infrared spectroscopy and chromatographic analysis. Nanoparticles were fabricated through the emulsion-solvent evaporation method and employed to encapsulate the lipophilic and antimicrobial agent usnic acid. Dynamic light scattering highlighted the obtainment of stable colloidal suspensions with dimensions of 40-160 nm. Biological evaluations demonstrated the antimicrobial efficacy against planktonic Newman strain and biofilm inhibition under fluidic conditions even for the unloaded nanoparticles. Additionally, the nanoparticles exhibited no cytotoxicity at concentrations ranging from 10 to 0.1 μg/mL while retaining antimicrobial activity, in contrast to the high cytotoxicity observed for free usnic acid. Overall, this approach offers a sustainable and scalable strategy to produce self-surfactant and intrinsically antimicrobial polymeric nanocarriers suitable for the systemic drug delivery of lipophilic compounds, smart implant coatings, and antibacterial topical formulations.
聚羟基脂肪酸酯（PHA）是一类天然存在的聚酯，在药物递送应用方面前景广阔。其疏水性使其能够包封亲脂性药物，提高生物利用度，但限制了胶体稳定性和生理相容性。表面活性剂对于改善纳米颗粒的尺寸稳定性、分散性、疏水基质的润湿性以及细胞相互作用至关重要，然而传统表面活性剂需要额外纯化且可能存在生理风险。自表面活性剂体系提供了一种可持续的替代方案。因此，本研究提出对PHA进行绿色化学改性以开发自表面活性剂体系。通过使用生物相容性离子液体牛磺酸胆碱（[Ch][Tau]）进行酰胺化反应，将亲水基团引入聚-3-羟基丁酸酯-3-羟基己酸酯（PHBHHx）主链上。这种方法无需使用有毒试剂和复杂的纯化过程。通过精确控制PHBHHx/[Ch][Tau]的摩尔比，制备出了具有不同疏水尾长的两亲结构，红外光谱和色谱分析证实了这一点。通过乳液-溶剂蒸发法制备了纳米颗粒，并用于包封亲脂性抗菌剂松萝酸。动态光散射结果表明获得了尺寸为40 - 160 nm的稳定胶体悬浮液。生物学评估表明，即使对于未负载药物的纳米颗粒，其对浮游的纽曼菌株也具有抗菌效果，并且在流体条件下具有生物膜抑制作用。此外，与游离松萝酸所观察到的高细胞毒性相比，纳米颗粒在浓度范围为10至0.1 μg/mL时没有细胞毒性，同时还保留了抗菌活性。总体而言，这种方法提供了一种可持续且可扩展的策略，用于生产适用于亲脂性化合物全身药物递送、智能植入涂层和抗菌外用制剂的自表面活性剂和具有内在抗菌性能的聚合物纳米载体。
