School of Pharmacy, Pharmacy Australia Centre of Excellence, University of Queensland, Brisbane, QLD 4102, Australia.
School of Pharmacy, Pharmacy Australia Centre of Excellence, University of Queensland, Brisbane, QLD 4102, Australia; Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia.
J Control Release. 2020 Aug 10;324:728-749. doi: 10.1016/j.jconrel.2020.05.002. Epub 2020 May 5.
Antibiotic resistance has become a global crisis, driving the exploration for novel antibiotics and novel treatment approaches. Among these research efforts two classes of antibiotics, bicyclic nitroimidazoles and antimicrobial peptides, have recently shown promise as novel antimicrobial agents with the possibility to treat multi-drug resistant infections. However, they suffer from the issue of poor oral bioavailability due to disparate factors: low solubility in the case of nitroimidazoles (BCS class II drugs), and low permeability in the case of peptides (BCS class III drugs). Moreover, antimicrobial peptides present another challenge as they are susceptible to chemical and enzymatic degradation, which can present an additional pharmacokinetic hurdle for their oral bioavailability. Formulation technologies offer a potential means for improving the oral bioavailability of poorly permeable and poorly soluble drugs, but there are still drawbacks and limitations associated with this approach. This review discusses in depth the challenges associated with oral delivery of nitroimidazoles and antimicrobial peptides and the formulation technologies that have been used to overcome these problems, including an assessment of the drawbacks and limitations associated with the technologies that have been applied. Furthermore, the potential for supercritical fluid technology to overcome the shortcomings associated with conventional drug formulation methods is reviewed.
抗生素耐药性已成为全球性危机，促使人们探索新型抗生素和新型治疗方法。在这些研究工作中，两类抗生素——双环硝咪唑类和抗菌肽——最近作为新型抗菌药物显示出希望，有可能治疗多药耐药感染。然而，由于不同因素，它们都存在口服生物利用度差的问题：硝咪唑类（BCS Ⅱ类药物）的溶解度低，肽类（BCS Ⅲ类药物）的渗透性低。此外，抗菌肽还面临另一个挑战，因为它们容易受到化学和酶的降解，这可能会对其口服生物利用度产生额外的药代动力学障碍。制剂技术为改善渗透性差和溶解度差的药物的口服生物利用度提供了一种潜在的手段，但这种方法仍然存在缺点和局限性。本综述深入讨论了口服给予硝咪唑类和抗菌肽所面临的挑战，以及已用于克服这些问题的制剂技术，包括对已应用技术的缺点和局限性的评估。此外，还回顾了超临界流体技术克服常规药物制剂方法缺点的潜力。
