>Acuitas therapeutics
lipid nanoparticle thecnology
https://www.mdpi.com/1999-4923/11/11/588/htm
Advances in Lipid and Metal Nanoparticles for Antimicrobial Peptide Delivery
by Marcin Makowski †ORCID,Ítala C. Silva †ORCID,Constança Pais do Amaral †ORCID,Sónia Gonçalves * andNuno C. Santos *ORCID
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2019, 11(11), 588; https://doi.org/10.3390/pharmaceutics11110588
Abstract
Antimicrobial peptides (AMPs) have been described as excellent candidates to overcome antibiotic resistance. Frequently, AMPs exhibit a wide therapeutic window, with low cytotoxicity and broad-spectrum antimicrobial activity against a variety of pathogens. In addition, some AMPs are also able to modulate the immune response, decreasing potential harmful effects such as sepsis. Despite these benefits, only a few formulations have successfully reached clinics. A common flaw in the druggability of AMPs is their poor pharmacokinetics, common to several peptide drugs, as they may be degraded by a myriad of proteases inside the organism. The combination of AMPs with carrier nanoparticles to improve delivery may enhance their half-life, decreasing the dosage and thus, reducing production costs and eventual toxicity. Here, we present the most recent advances in lipid andmetal nanodevices for AMP delivery, with a special focus onmetal nanoparticles and liposome formulations.
-
Conclusions and Future Perspectives
Worrisomely, bacteria evolve faster than we develop new antibiotics [204]. We have a potentially unexploited arsenal of antibiotics in AMPs. Nonetheless, the poor pharmacokinetics of peptide drugs is limiting their use. The combination of AMPs with drug delivery systems such as liposomes and metal nanoparticles can be fundamental for their implementation. At this point, the development of suitable nanoparticles to deliver AMPs is a major bottleneck for the implementation of AMPs in the clinical practice [137]. Indeed, the majority of nanodrugs under clinical trials are anticancer and antimicrobial, revealing the increasing interest in this matter [205].
Since 1995, up to 50 nanopharmaceuticals have received FDA approval. The search of the term ‘nano’ yields 95 active clinical trials in the Clinical Trials website (May 2019) [206]. A large tendency is for micelles and protein-based NPs, while an increased use of metal NPs can also be noticed [207]. Peptides are still one of the major pharmaceutical market targets, but their future as drugs is still fragile. Thus,the upcoming Magic Bullet might well be a nanoparticle conjugated with AMPs.
Despite the great advances in nanomedicine and its rapid growth, there are still several obstacles to their progression to clinics. A large gap between the encouraging in vitro results, the rather disappointing pre-clinical results, and the low impact in clinical settings can often be found. NP-host interactions are difficult to tackle. In pre-clinical studies, it has been pointed out that the need of immunodeficient mice for xenograft tumor transplantation may be leading us to overlook immune interactions that hamper NPs activity. Sound strategies are needed to investigate cytotoxicity, inflammatory response and immune response, not only in cell culture, but also in clinical isolates, as there is a need for further in vivo studies to ensure the safe use of NPs.Long-term toxicity studies are also needed to better understand the implications of silver and gold deposition in the human body. The use of lipids in nanoparticles offers more possibilities of drug encapsulation and increases the possibilities of acceptance as DDSs by the regulatory agencies, due to their biodegradability and common occurrence in biological systems.
Based on the findings reviewed here, research and clinics should come together to improve the potentiality of these DDSs, which may have an important role in human healthcare. It is imperative to overview the approaches of AMP-NP formulations to improve therapeutics and reduce side effects.