Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands; Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, 45139-56184 Zanjan, Iran.
Drug Discov Today. 2022 Aug;27(8):2309-2321. doi: 10.1016/j.drudis.2022.04.014. Epub 2022 Apr 20.
Oral delivery is preferred over other routes of drug administration by both patients and physicians. The bioavailability of some therapeutics that are delivered via the oral route is restricted due to the protease- and bacteria-rich environment in the gastrointestinal tract, and by the pH variability along the delivery route. Given these harsh environments, the oral delivery of therapeutic macromolecules is complicated and remains challenging. Various formulation approaches, including the use of permeation enhancers and nanosized carriers, as well as chemical alteration of the drug structure, have been studied as ways to improve the oral absorption of macromolecular drugs. Nevertheless, the bioavailability of marketed oral peptide medicines is often relatively poor. This review highlights the most recent and promising physical methods for improving the oral bioavailability of macromolecules such as peptides. These methods include microneedle injections, high-speed stream injectors, magnetic drug targeting, expandable hydrogels, and iontophoresis. We highlight the potential and challenges of these new technologies, which may impact the future approaches used by pharmaceutical companies to create more efficient and safer orally administered macromolecules.
口服给药在患者和医生中都优于其他给药途径。由于胃肠道中蛋白酶和细菌丰富的环境以及沿着给药途径的 pH 值变化,一些通过口服途径给药的治疗药物的生物利用度受到限制。鉴于这些恶劣的环境,治疗性大分子的口服递送变得复杂且仍然具有挑战性。各种制剂方法,包括使用渗透增强剂和纳米载体以及药物结构的化学修饰,已被研究用于提高大分子药物的口服吸收。然而,上市的口服肽类药物的生物利用度往往相对较差。本综述重点介绍了最近和有前途的物理方法,可提高肽等大分子的口服生物利用度。这些方法包括微针注射、高速流注注射器、磁药物靶向、可膨胀水凝胶和离子电渗疗法。我们强调了这些新技术的潜力和挑战,这些技术可能会影响制药公司未来用于制造更有效和更安全的口服大分子的方法。
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