Barbery Brian George, Lukesh Nicole Rose, Bachelder Eric M, Ainslie Kristy M
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, 27599, USA.
Small. 2025 Feb 16:e2409422. doi: 10.1002/smll.202409422.
The field of immunotherapeutics is rapidly evolving with the advent of cell therapies, complex biologics, and a host of other compounds. Polymeric carriers are often used to tune the safety and efficacy profiles of these novel drugs. Despite their prevalence in pre-clinical and clinical applications, non-degradable materials present delivery challenges including diffusion-limited release, frustrated phagocytosis, and limited clearance. In contrast, biodegradable polymeric systems provide a safer alternative in addition to displaying advantageous properties for the delivery of immunotherapies. In this review, discussion of polymers including poly(lactic-co-glycolic acid) (PLGA), poly(beta-amino esters) (PBAEs), acetalated dextran (Ace-DEX), chitosan, alginate, and hyaluronic acid (HA) as immunomodulatory biomaterial carriers suggest that a variety of systems can be used to generate tailored formulations for different therapeutic payloads and disease indications. These carrier systems can enhance the delivery of immunotherapies via tunable degradation rates, enhanced antigen-presentation, and inherent immunomodulatory properties of the biomaterials, among other mechanisms. Polymers formulated for immunomodulatory applications can be synthetic, semi-synthetic, or naturally derived. Therefore, it is crucial to consider the environmental impact of polymer sources, particle fabrication methods, and solvent usage to sustainably develop effective immunomodulatory therapies in this evolving field.
随着细胞疗法、复杂生物制剂以及许多其他化合物的出现,免疫治疗领域正在迅速发展。聚合物载体常被用于调节这些新型药物的安全性和有效性。尽管它们在临床前和临床应用中很普遍,但不可降解材料存在递送挑战,包括扩散限制释放、吞噬受阻和清除受限。相比之下,可生物降解的聚合物系统除了在免疫治疗递送方面显示出有利特性外,还提供了一种更安全的选择。在这篇综述中,对包括聚乳酸-乙醇酸共聚物(PLGA)、聚(β-氨基酯)(PBAE)、缩醛化葡聚糖(Ace-DEX)、壳聚糖、藻酸盐和透明质酸(HA)等聚合物作为免疫调节生物材料载体的讨论表明,可以使用多种系统为不同的治疗载荷和疾病适应症生成定制配方。这些载体系统可以通过可调节的降解速率、增强的抗原呈递以及生物材料固有的免疫调节特性等多种机制来增强免疫治疗的递送。用于免疫调节应用的聚合物可以是合成的、半合成的或天然衍生的。因此,在这个不断发展的领域中,考虑聚合物来源、颗粒制造方法和溶剂使用对环境的影响对于可持续开发有效的免疫调节疗法至关重要。