Ahsan Anam, Thomas Nicky, Barnes Timothy J, Subramaniam Santhni, Loh Thou Chen, Joyce Paul, Prestidge Clive A
Centre for Pharmaceutical Innovation, University of South Australia, Adelaide, SA 5000, Australia.
Pharmaceutics. 2024 Mar 14;16(3):396. doi: 10.3390/pharmaceutics16030396.
The opportunistic bacteria growing in biofilms play a decisive role in the pathogenesis of chronic infectious diseases. Biofilm-dwelling bacteria behave differently than planktonic bacteria and are likely to increase resistance and tolerance to antimicrobial therapeutics. Antimicrobial adjuvants have emerged as a promising strategy to combat antimicrobial resistance (AMR) and restore the efficacy of existing antibiotics. A combination of antibiotics and potential antimicrobial adjuvants, (e.g., extracellular polymeric substance (EPS)-degrading enzymes and quorum sensing inhibitors (QSI) can improve the effects of antibiotics and potentially reduce bacterial resistance). In addition, encapsulation of antimicrobials within nanoparticulate systems can improve their stability and their delivery into biofilms. Lipid nanocarriers (LNCs) have been established as having the potential to improve the efficacy of existing antibiotics in combination with antimicrobial adjuvants. Among them, liquid crystal nanoparticles (LCNPs), liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) are promising due to their superior properties compared to traditional formulations, including their greater biocompatibility, higher drug loading capacity, drug protection from chemical or enzymatic degradation, controlled drug release, targeted delivery, ease of preparation, and scale-up feasibility. This article reviews the recent advances in developing various LNCs to co-deliver some well-studied antimicrobial adjuvants combined with antibiotics from different classes. The efficacy of various combination treatments is compared against bacterial biofilms, and synergistic therapeutics that deserve further investigation are also highlighted. This review identifies promising LNCs for the delivery of combination therapies that are in recent development. It discusses how LNC-enabled co-delivery of antibiotics and adjuvants can advance current clinical antimicrobial treatments, leading to innovative products, enabling the reuse of antibiotics, and providing opportunities for saving millions of lives from bacterial infections.
在生物膜中生长的机会性细菌在慢性传染病的发病机制中起决定性作用。生活在生物膜中的细菌与浮游细菌的行为不同，并且可能增加对抗菌治疗的抗性和耐受性。抗菌佐剂已成为对抗抗菌耐药性（AMR）和恢复现有抗生素疗效的一种有前景的策略。抗生素与潜在的抗菌佐剂（例如，细胞外聚合物（EPS）降解酶和群体感应抑制剂（QSI））的组合可以提高抗生素的效果，并可能降低细菌耐药性。此外，将抗菌剂封装在纳米颗粒系统中可以提高其稳定性以及它们向生物膜中的递送。脂质纳米载体（LNC）已被证实有潜力与抗菌佐剂联合提高现有抗生素的疗效。其中，液晶纳米颗粒（LCNP）、脂质体、固体脂质纳米颗粒（SLN）和纳米结构脂质载体（NLC）因其与传统制剂相比具有优异的性能而颇具前景，包括更高的生物相容性、更高的载药量、药物免受化学或酶降解、可控的药物释放、靶向递送、易于制备以及扩大规模的可行性。本文综述了开发各种LNC以共同递送一些经过充分研究的抗菌佐剂与不同类别的抗生素的最新进展。比较了各种联合治疗对细菌生物膜的疗效，并强调了值得进一步研究的协同疗法。这篇综述确定了近期正在开发的用于联合治疗递送的有前景的LNC。它讨论了如何通过LNC实现抗生素和佐剂的共同递送可以推动当前的临床抗菌治疗，带来创新产品，实现抗生素的再利用，并为拯救数百万人免受细菌感染提供机会。
