Biodistribution of the cationic host defense peptide LL-37 using SPECT/CT.

Human cathelicidin LL-37, a cationic host defense peptide (CHDP), has several important physiological roles, including antimicrobial activity, immune modulation, and wound healing, and is a being investigated as a therapeutic candidate for several indications. While the effects of endogenously produced LL-37 are well studied, the biodistribution of exogenously administered LL-37 are less known. Here we assess the biodistribution of a gallium-67 labeled variant of LL-37 using nuclear imaging techniques over a 48 h period in healthy mice.

Nanogel delivery systems for cationic peptides: More than a 'One Size Fits All' solution.

Self-assembled hyaluronic acid-based nanogels are versatile drug carriers due to their biodegradable nature and gentle preparation conditions, making them particularly interesting for delivery of peptide therapeutics. This study aims to elucidate the relation between peptide structure and encapsulation in a nanogel. Key peptide properties that affect encapsulation in octenyl succinic anhydride-modified hyaluronic acid nanogels were identified as we explored the effect on nanogel characteristics using 12 peptides with varying charge and hydrophobicity.

Encapsulation in oleyl-modified hyaluronic acid nanogels substantially improves the clinical potential of the antimicrobial peptides SAAP-148 and Ab-Cath.

Antimicrobial peptides (AMPs) are promising alternatives to antibiotics for treatment of antimicrobial resistant (AMR) bacterial infections. However, their narrow therapeutic window due to in vivo toxicity and limited stability hampers their clinical use. Here, we evaluated encapsulation of two amphiphilic AMPs, SAAP-148 and snake cathelicidin Ab-Cath, into oleyl-modified hyaluronic acid (OL-HA) nanogels to improve their selectivity index.

Encapsulation of SAAP-148 in Octenyl Succinic Anhydride-Modified Hyaluronic Acid Nanogels for Treatment of Skin Wound Infections.

Chronic wound infections colonized by bacteria are becoming more difficult to treat with current antibiotics due to the development of antimicrobial resistance (AMR) as well as biofilm and persister cell formation. Synthetic antibacterial and antibiofilm peptide (SAAP)-148 is an excellent alternative for treatment of such infections but suffers from limitations related to its cationic peptidic nature and thus instability and possible cytotoxicity, resulting in a narrow therapeutic window. Here, we evaluated SAAP-148 encapsulation in nanogels composed of octenyl succinic anhydride (OSA)-modified hyaluronic acid (HA) to circumvent these limitations.

Current Advances in Lipid and Polymeric Antimicrobial Peptide Delivery Systems and Coatings for the Prevention and Treatment of Bacterial Infections.

Bacterial infections constitute a threat to public health as antibiotics are becoming less effective due to the emergence of antimicrobial resistant strains and biofilm and persister formation. Antimicrobial peptides (AMPs) are considered excellent alternatives to antibiotics; however, they suffer from limitations related to their peptidic nature and possible toxicity. The present review critically evaluates the chemical characteristics and antibacterial effects of lipid and polymeric AMP delivery systems and coatings that offer the promise of enhancing the efficacy of AMPs, reducing their limitations and prolonging their half-life.

Nanoparticle-mediated pulmonary drug delivery: state of the art towards efficient treatment of recalcitrant respiratory tract bacterial infections.

Recalcitrant respiratory tract infections caused by bacteria have emerged as one of the greatest health challenges worldwide. Aerosolized antimicrobial therapy is becoming increasingly attractive to combat such infections, as it allows targeted delivery of high drug concentrations to the infected organ while limiting systemic exposure. However, successful aerosolized antimicrobial therapy is still challenged by the diverse biological barriers in infected lungs.

Monosized Polymeric Microspheres Designed for Passive Lung Targeting: Biodistribution and Pharmacokinetics after Intravenous Administration.

Local as well as systemic therapy is often used to treat bacterial lung infections. Delivery of antibiotics to the vascular side of infected lung tissue using lung-targeting microspheres (MS) is a good alternative to conventional administration routes, allowing for localized high levels of antibiotics. This delivery route can also complement inhaled antibiotic therapy, especially in the case of compromised lung function.

Ultrasmall TPGS-PLGA Hybrid Nanoparticles for Site-Specific Delivery of Antibiotics into Biofilms in Lungs.

Inhaled antibiotic treatment of cystic fibrosis-related bacterial biofilm infections is challenging because of the pathological environment of the lungs. Here, we present an "environment-adaptive" nanoparticle composed of a solid poly lactic--glycolic acid (PLGA) core and a mucus-inert, enzymatically cleavable shell of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the site-specific delivery of antibiotics to bacterial biofilms via aerosol administration. The hybrid nanoparticles with ultrasmall size were self-assembled via a nanoprecipitation process by using a facile microfluidic method.

Utilizing nanoparticles for improving anti-biofilm effects of azithromycin: A head-to-head comparison of modified hyaluronic acid nanogels and coated poly (lactic-co-glycolic acid) nanoparticles.

Hypothesis: The widespread resistance of bacteria to traditional antibiotic treatments has expedited the search for novel therapies against these pathogens. The hypothesis of this work is that two distinctively different polymeric delivery systems, specifically D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles and octenyl succinic anhydride-modified low molecular weight hyaluronic acid (OSA-HA) nanogels may be used to substantially improve the properties of azithromycin, allowing its use for effective treatment of Pseudomonas aeruginosa biofilm infections.

Experiments: Azithromycin was encapsulated in both delivery systems and the physicochemical properties of the loaded delivery systems, including size, surface charge and drug loading were evaluated.

Hyaluronic acid-based nanogels improve in vivo compatibility of the anti-biofilm peptide DJK-5.

Anti-biofilm peptides are a subset of antimicrobial peptides and represent promising broad-spectrum agents for the treatment of bacterial biofilms, though some display host toxicity in vivo. Here we evaluated nanogels composed of modified hyaluronic acid for the encapsulation of the anti-biofilm peptide DJK-5 in vivo. Nanogels of 174 to 194 nm encapsulating 33-60% of peptide were created.

Biopolymer nanogels improve antibacterial activity and safety profile of a novel lysine-based α-peptide/β-peptoid peptidomimetic.

Infections caused by Pseudomonas aeruginosa are associated with high morbidity and mortality, especially in immunocompromised patients. These bacteria frequently grow within a biofilm matrix, rendering therapy with conventional antibiotics inefficient; a fact that emphasizes the need for new treatment strategies. Antimicrobial peptidomimetics constitute potential alternatives to traditional antimicrobial agents.

Lipid Shell-Enveloped Polymeric Nanoparticles with High Integrity of Lipid Shells Improve Mucus Penetration and Interaction with Cystic Fibrosis-Related Bacterial Biofilms.

Nanoparticle (NP) mediated drug delivery into viscous biomatrices, e.g., mucus and bacterial biofilms, is challenging.

Combining diagnostic methods for antimicrobial susceptibility testing - A comparative approach.

Background: The minimum inhibitory concentration (MIC) is a measure of antimicrobial susceptibility testing (AST) of a given antibiotic but provides insufficient information when bacterial killing is crucial, e.g., when treating immunocompromised patients.

Ciprofloxacin-loaded sodium alginate/poly (lactic-co-glycolic acid) electrospun fibrous mats for wound healing.

Wound dressings should ideally be able to maintain high humidity, remove excess wound exudate, permit thermal insulation, provide certain mechanical strength, and in some cases deliver antibiotics to prevent infections. Until now, none of the existing wound dressing products can meet all these requirements. To design a wound dressing with as many of the aforementioned features as possible, in this study, we attempted to prepare ciprofloxacin (CIP), an antibiotic, loaded electrospun hydrophobic poly (lactic-co-glycolic acid) (PLGA) fibrous mats modified with hydrophilic sodium alginate (ALG) microparticles.

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients: Challenges and Drug Delivery Approaches.

Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for growth, leading to re-infection of the lungs, even after clearing an initial lung infection.