Dorraj Golnar, Carreras Juan Jose, Nunez Hugo, Abushammala Issam, Melero Ana
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain.
Pharmaceutical science research center, Shahid Beheshti university of Medical Science, Tehran, Iran.
Curr Gene Ther. 2017;17(2):89-104. doi: 10.2174/1566523217666170510163038.
Gene therapy has experimented an increasing attention in the last decades, due to its enormous potential applications in the medical field. It can be defined as the use of genes or genetic material (DNA, RNA, oligonucleotides) to treat or prevent a disease state, generally a geneticbased one.
Other applications, like treating viral, bacterial or parasite infections or development of vaccines are gaining also interest. Efficient gene therapy is mainly dependent on the ability of the highly labile genetic material to reach the therapeutic target. For this purpose, different delivery systems have been designed and extensively investigated. Nanoparticles offer a broad range of possibilities in design, being prepared using biocompatible and biodegradable excipients, being therefore generally considered as safe.
Oral delivery of the genetic material is also a great challenge, due to the complexity of this specific biological barrier. Special attention to all the intrinsic hazards for gene delivery due to the barrier must be taken into account during the particle design process. Particle design will also allow targeting to specific sites of the gastrointestinal tract. Solid lipid nanoparticles have been extensively studied in the oral drug delivery field, and also in gene delivery through other administration routes, but still not explored in oral gene delivery. In this manuscript, design considerations and particle-cell interaction mechanisms will be extensively reviewed, focusing on the oral route to encourage the scientific community to explore these valuable carriers for oral gene delivery.
在过去几十年中,基因治疗因其在医学领域的巨大潜在应用而受到越来越多的关注。它可以被定义为使用基因或遗传物质(DNA、RNA、寡核苷酸)来治疗或预防疾病状态,通常是基于基因的疾病。
其他应用,如治疗病毒、细菌或寄生虫感染或开发疫苗,也越来越受到关注。高效的基因治疗主要取决于高度不稳定的遗传物质到达治疗靶点的能力。为此,人们设计并广泛研究了不同的递送系统。纳米颗粒在设计上提供了广泛的可能性,它们使用生物相容性和可生物降解的辅料制备,因此通常被认为是安全的。
由于这种特定生物屏障的复杂性,遗传物质的口服递送也是一个巨大的挑战。在颗粒设计过程中,必须特别关注由于该屏障导致的基因递送的所有内在风险。颗粒设计还将允许靶向胃肠道的特定部位。固体脂质纳米颗粒在口服药物递送领域以及通过其他给药途径的基因递送中都得到了广泛研究,但在口服基因递送中尚未得到探索。在本手稿中,将广泛综述设计考虑因素和颗粒 - 细胞相互作用机制,重点关注口服途径,以鼓励科学界探索这些用于口服基因递送的有价值的载体。