Colistin- and amikacin-loaded lipid-based drug delivery systems for resistant gram-negative lung and wound bacterial infections

Vairo, Claudia; Vidal, Maria Villar; Hernández, Rosa Marı́a; Igartua, Manoli; Villullas, Silvia

doi:10.1016/j.ijpharm.2023.122739

Cited by 13 publications

(6 citation statements)

References 86 publications

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“…Lipid nanoparticles are one of the most promising vehicles of the family thanks to their elevated degree of biocompatibility, encapsulation efficiency, and customization [80]. Among them, the two types frequently used for the treatment of microbial infections are solid lipid nanoparticles and liposomes [81,82]; this review will discuss the main features and some of their technological evolutions, namely functionalized liposomes and exosomes, under the label of innovative phospholipid carriers (IPCs).…”

Section: Innovative Phospholipid Carriers (Ipcs)mentioning

confidence: 99%

“…In line with these results, other groups have investigated the potential amelioration of treatments against potent bacteria with the encapsulation of traditional, not-moreefficacious antibiotics in liposomal formulations, obtaining in this way promising results [108][109][110]: among them, a case study was represented by two liposomal ciprofloxacin products, Lipoquin and Pulmaquin, for inhalation use, which permits ciprofloxacin to be utilized again as a first-line choice when the patient is facing complicated lung infections, even in cystic fibrosis-based (CF) scenarios [111,112]; sadly, both formulations were discontinued in 2022 since decisive data on their functionality were not achieved after an ORBIT phase 3 study. A different, brilliant destiny was instead achieved by liposomal formulations of amikacin (Arikayce), which have been tested with remarkable outcomes in CF, particularly in non-CF severe lung illnesses alone, and in combination with colistin [81,113].…”

Section: Innovative Phospholipid Carriers Versus Antimicrobial Resist...mentioning

confidence: 99%

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Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance

Nicolosi,

Petronio Petronio,

Russo

et al. 2023

IJMS

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The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.

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Section: Innovative Phospholipid Carriers (Ipcs)mentioning

confidence: 99%

Section: Innovative Phospholipid Carriers Versus Antimicrobial Resist...mentioning

confidence: 99%

Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance

Nicolosi,

Petronio Petronio,

Russo

et al. 2023

IJMS

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“…Furthermore, AMR raises the global burden of medical interventions due to prolonged hospital stays and expensive drug treatments. [1,2] One of the critical factors in the increase in AMR is inappropriately prescribed antibiotics. This condition is common in children.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of naringin on colistin‐induced damage in rat testicular tissue: Modulating the levels of Nrf‐2/HO‐1, AKT‐2/FOXO1A, Bax/Bcl2/Caspase‐3, and Beclin‐1/LC3A/LC3B signaling pathways

Kankılıç,

Şimşek,

Akaras

et al. 2024

J Biochem & Molecular Tox

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Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug‐resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti‐inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL‐induced toxicity in testicular tissue. Thirty‐five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50 or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2‐related factor‐2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage.

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“…Several strategies for colistin toxicity reduction have already been assessed over the years that mainly focus on facilitating or encapsulating colistin, aiming to decrease the undesired interactions of colistin causing toxicity. ,− E.g., conjugation with hyaluronan-chitosan derivatives has been investigated, but also drug delivery systems like colistin loading into liposomes, chelating micelles, aerosolizable particles, nanostructured lipid carriers (NLCs), , solid lipid nanoparticles (SLNs), poly(lactic- co -glycolic acid) (PLGA) nanoparticles, and complexation into coacervates . In the development of drug delivery methods for colistin, several factors need to be controlled, like solubility, retainability, bioavailability, and functionality.…”

Section: Introductionmentioning

confidence: 99%

“…In the development of drug delivery methods for colistin, several factors need to be controlled, like solubility, retainability, bioavailability, and functionality. Currently, the main concerns with colistin drug delivery are its stability, chemical alteration, and poor water solubility, leading to low bioavailability. ,, To resolve these challenges, going deeper into complex coacervation could be a viable strategy as it does not require any chemical modification of the drug and allows for effective encapsulation of water-soluble drugs. , However, this requires sufficient colloidal stability of the formed complexes. Complexation of colistin could improve the retainability and stability by protecting the drug from degradation and enhancing its therapeutic efficacy in various pharmaceutical formulations.…”

Section: Introductionmentioning

confidence: 99%

Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers

Vogelaar,

Agger,

Reseland

et al. 2024

Biomacromolecules

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To combat the ever-growing increase of multidrugresistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

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Colistin- and amikacin-loaded lipid-based drug delivery systems for resistant gram-negative lung and wound bacterial infections

Cited by 13 publications

References 86 publications

Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance

Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance

Protective effects of naringin on colistin‐induced damage in rat testicular tissue: Modulating the levels of Nrf‐2/HO‐1, AKT‐2/FOXO1A, Bax/Bcl2/Caspase‐3, and Beclin‐1/LC3A/LC3B signaling pathways

Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers

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