^99mTc-Labeled, Colistin Encapsulated, Theranostic Liposomes for Pseudomonas aeruginosa Infection

Infectious diseases are still the major issue not only due to antibiotic resistance but also causing deaths if not diagnosed at early-stages. Different approaches including nanosized drug delivery systems and theranostics are researched to overcome antibiotic resistance, decrease the side effects of antibiotics, improve the treatment response, and early diagnose. Therefore, in the present study, nanosized, radiolabeled with ^99mTc, colistin encapsulated, neutral and cationic liposome formulations were prepared as the theranostic agent for Pseudomonas aeruginosa infections. Liposomes exhibited appropriate physicochemical properties thanks to their nano-particle size (between 173 and 217 nm), neutral zeta potential value (about − 6.5 and 2.8 mV), as well as encapsulation efficiency of about 75%. All liposome formulations were radiolabeled with over 90% efficiency, and the concentration of stannous chloride was found as 1 mg.mL^−1 to obtain maximum radiolabeling efficiency. In alamar blue analysis, neutral liposome formulations were found more biocompatible compared with the cationic formulations. Neutral colistin encapsulated liposomes were found to be more effective against P. aeruginosa strain according to their time-dependent antibacterial effect, in addition to their highest bacterial binding capacity. As conclusion, theranostic, nanosized, colistin encapsulated, neutral liposome formulations were found as promising agents for the imaging and treating of P. aeruginosa infections.

[1]  T. Srichana,et al.  Colistin sulfate-sodium deoxycholate sulfate micelle formulations; molecular interactions, cell nephrotoxicity and bioactivity , 2022, Journal of Drug Delivery Science and Technology.

[2]  Mohammad Mashreghi,et al.  Redox-sensitive doxorubicin liposome: a formulation approach for targeted tumor therapy , 2022, Scientific Reports.

[3]  F. Raffaelli,et al.  New Drugs for the Treatment of Pseudomonas aeruginosa Infections with Limited Treatment Options: A Narrative Review , 2022, Antibiotics.

[4]  M. Kim,et al.  A novel dual-labeled small peptide as a multimodal imaging agent for targeting wild-type EGFR in tumors , 2022, PloS one.

[5]  A. Nalbantsoy,et al.  Design and evaluation of erucic acid-phytosphingosine structured cationic nanoemulsions as a plasmid DNA delivery system against breast cancer cells , 2022, Pharmaceutical development and technology (Print).

[6]  Merve Karpuz,et al.  Lipid‐Based Drug Delivery Systems and Their Role in Infection and Inflammation Imaging , 2021, Nanoengineering of Biomaterials.

[7]  S. N. Topkaya,et al.  Electrochemical Analysis of Liposome‐Encapsulated Colistimethate Sodium , 2021, Electroanalysis.

[8]  S. Mushtaq,et al.  Recent Progress in Technetium-99m-Labeled Nanoparticles for Molecular Imaging and Cancer Therapy , 2021, Nanomaterials.

[9]  M. Amin,et al.  Brain targeting efficiency of intranasal clozapine-loaded mixed micelles following radio labeling with Technetium-99m , 2021, Drug delivery.

[10]  A. Alstrup,et al.  Radiotracers for Bone Marrow Infection Imaging , 2021, Molecules.

[11]  Xiaosi Li,et al.  Zero-Order Controlled Release of Water-Soluble Drugs Using a Marker Pen Platform , 2021, ACS omega.

[12]  M. A. Motaleb,et al.  Formulation of chitosan coated nanoliposomes for the oral delivery of colistin sulfate: in vitro characterization, 99mTc-radiolabeling and in vivo biodistribution studies , 2021, Drug development and industrial pharmacy.

[13]  S. Vranješ-Đurić,et al.  Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[14]  A. Fakhari,et al.  Preparation, biodistribution and dosimetry study of Tc-99m labeled N-doped graphene quantum dot nanoparticles as a multimodular radiolabeling agent , 2021 .

[15]  Q. Bai,et al.  Self-assembled ultrasmall silver nanoclusters on liposome for topical antimicrobial delivery. , 2021, Colloids and surfaces. B, Biointerfaces.

[16]  Zeynep Senyigit,et al.  Radiolabeled Tedizolid Phosphate Liposomes for Topical Application: Design, Characterization, and Evaluation of Cellular Binding Capacity , 2021, AAPS PharmSciTech.

[17]  P. Gawne,et al.  Radiolabelling of nanomaterials for medical imaging and therapy. , 2021, Chemical Society reviews.

[18]  Nikita,et al.  Liposomes as multifaceted delivery system in the treatment of osteoporosis , 2021, Expert opinion on drug delivery.

[19]  C. Castagnoli,et al.  Enhanced Antimicrobial and Antibiofilm Effect of New Colistin-Loaded Human Albumin Nanoparticles , 2021, Antibiotics.

[20]  P. Behzadi,et al.  It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa , 2021, Antibiotics.

[21]  E. D. Di Domenico,et al.  Characterization of the virulence of Pseudomonas aeruginosa strains causing ventilator-associated pneumonia , 2020, BMC Infectious Diseases.

[22]  A. Rodrigues,et al.  Colistin Update on Its Mechanism of Action and Resistance, Present and Future Challenges , 2020, Microorganisms.

[23]  G. Esendagli,et al.  Diagnostic And Therapeutic Evaluation Of Folate-Targeted Paclitaxel And Vinorelbine Encapsulated Theranostic Liposomes For Non-Small Cell Lung Cancer. , 2020, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[24]  Kevin J. McHugh,et al.  Zero-order drug delivery: State of the art and future prospects. , 2020, Journal of controlled release : official journal of the Controlled Release Society.

[25]  T. Andresen,et al.  Quantitative determination of 64Cu-liposome accumulation at inflammatory and infectious sites: Potential for future theranostic system. , 2020, Journal of controlled release : official journal of the Controlled Release Society.

[26]  T. Kanazawa,et al.  The effects of surface properties of liposomes on their activity against Pseudomonas aeruginosa PAO-1 biofilm , 2020 .

[27]  G. Esendagli,et al.  Design and in vitro evaluation of folate-targeted, co-drug encapsulated theranostic liposomes for non-small cell lung cancer , 2020, Journal of Drug Delivery Science and Technology.

[28]  Xiaosi Li,et al.  Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules , 2020, Frontiers in Bioengineering and Biotechnology.

[29]  Evren Gundogdu,et al.  Current update on nanoplatforms as therapeutic and diagnostic tools: A review for the materials used as nanotheranostics and imaging modalities , 2020, Asian journal of pharmaceutical sciences.

[30]  Jia-You Fang,et al.  Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances , 2020, Frontiers in Chemistry.

[31]  A. Ozer,et al.  99mTc-radiolabeled Levofloxacin and micelles as infection and inflammation imaging agents , 2020, Journal of Drug Delivery Science and Technology.

[32]  Zhuang Liu,et al.  The enhanced permeability and retention effect based nanomedicine at the site of injury , 2020, Nano Research.

[33]  Zeynep Senyigit,et al.  The effect of radiolabeled nanostructured lipid carrier systems containing imatinib mesylate on NIH-3T3 and CRL-1739 cells , 2020, Drug delivery.

[34]  Y. Doi,et al.  Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019) , 2020, Emerging microbes & infections.

[35]  F. Alexis,et al.  Radioactive polymeric nanoparticles for biomedical application , 2020, Drug delivery.

[36]  J. Li,et al.  Inhalable Liposomal Powder formulations for Co-delivery of Synergistic Ciprofloxacin and Colistin against Multi-drug Resistant Gram-negative Lung Infections. , 2019, International journal of pharmaceutics.

[37]  L. Deng,et al.  Adhesive liposomes loaded onto an injectable, self-healing and antibacterial hydrogel for promoting bone reconstruction , 2019, NPG Asia Materials.

[38]  C. Ferreira,et al.  Ag2WO4 nanoparticles radiolabeled with technetium-99m: a potential new tool for tumor identification and uptake , 2019, Journal of Radioanalytical and Nuclear Chemistry.

[39]  Kelly A McCarthy,et al.  Radiolabeled Cationic Peptides for Targeted Imaging of Infection , 2019, Contrast media & molecular imaging.

[40]  T. Haertlé,et al.  World Health Organization Report: Current Crisis of Antibiotic Resistance , 2019, BioNanoScience.

[41]  S. Eğrilmez,et al.  The Utility of Colistin in Multiple Drug-Resistant Pseudomonas aeruginosa Bacterial Keratitis in a Kaposi’s Sarcoma Patient , 2019, Turkish journal of ophthalmology.

[42]  D. Ahmadvand,et al.  The bactericidal effect of lysostaphin coupled with liposomal vancomycin as a dual combating system applied directly on methicillin-resistant Staphylococcus aureus infected skin wounds in mice , 2019, International journal of nanomedicine.

[43]  M. Bischoff,et al.  Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica , 2019, Advanced healthcare materials.

[44]  C. Sayes,et al.  Synthesis and characterization of nanometer-sized liposomes for encapsulation and microRNA transfer to breast cancer cells , 2019, International journal of nanomedicine.

[45]  Dnyaneshwar Kalyane,et al.  Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. , 2019, Materials science & engineering. C, Materials for biological applications.

[46]  D. Álvarez-Hernández,et al.  Pseudomonas aeruginosa: patogenicidad y resistencia antimicrobiana en la infección urinaria , 2019, Revista chilena de infectología.

[47]  L. Columbus,et al.  Quantifying Carcinoembryonic Antigen-like Cell Adhesion Molecule-Targeted Liposome Delivery Using Imaging Flow Cytometry. , 2019, Molecular pharmaceutics.

[48]  D. Álvarez-Hernández,et al.  [Pseudomonas aeruginosa: Pathogenicity and antimicrobial resistance in urinary tract infection]. , 2019, Revista chilena de infectología.

[49]  L. Chuah,et al.  Characterization, optimization, and in vitro evaluation of Technetium-99m-labeled niosomes , 2019, International journal of nanomedicine.

[50]  R. Santos-Oliveira,et al.  Dose calculation of radioactive nanoparticles: first considerations for the Design of Theranostic Agents , 2018, Biomedical microdevices.

[51]  A. Misra,et al.  Colloidally Stable Small Unilamellar Stearyl Amine Lipoplexes for Effective BMP-9 Gene Delivery to Stem Cells for Osteogenic Differentiation , 2018, AAPS PharmSciTech.

[52]  Jian Li,et al.  Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa , 2018, Pharmaceutical Research.

[53]  U. Bakowsky,et al.  Hypericin Loaded Liposomes for Anti‐Microbial Photodynamic Therapy of Gram‐Positive Bacteria , 2018 .

[54]  P. Uchil,et al.  Analysis of Cell Viability by the alamarBlue Assay. , 2018, Cold Spring Harbor protocols.

[55]  H. Takeuchi,et al.  Effects of cationic liposomes with stearylamine against virus infection , 2018, International journal of pharmaceutics.

[56]  M. R. Mozafari,et al.  Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems , 2018, Pharmaceutics.

[57]  A. Signore,et al.  Leukocyte Imaging of the Diabetic Foot. , 2018, Current pharmaceutical design.

[58]  N. Obeidat,et al.  Antimicrobial resistance and putative virulence genes of Pseudomonas aeruginosa isolates from patients with respiratory tract infection. , 2018, Germs.

[59]  Doug W. Smith,et al.  Advantages and Limitations of Current Imaging Techniques for Characterizing Liposome Morphology , 2018, Front. Pharmacol..

[60]  G. Kahlmeter,et al.  Antimicrobial susceptibility testing of colistin - evaluation of seven commercial MIC products against standard broth microdilution for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[61]  R. Kulshreshtha,et al.  Enhanced efficacy of anti-miR-191 delivery through stearylamine liposome formulation for the treatment of breast cancer cells. , 2017, International journal of pharmaceutics.

[62]  Rachael M. Crist,et al.  Zeta potential: a case study of cationic, anionic, and neutral liposomes , 2017, Analytical and Bioanalytical Chemistry.

[63]  Li Yang,et al.  Electrostatically entrapped colistin liposomes for the treatment of Pseudomonas aeruginosa infection , 2017, Pharmaceutical development and technology.

[64]  Wen-juan Wei,et al.  Synergy against extensively drug-resistant Acinetobacter baumannii in vitro by two old antibiotics: colistin and chloramphenicol. , 2017, International journal of antimicrobial agents.

[65]  D. Ling,et al.  Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy , 2017, Theranostics.

[66]  Yuko Nakamura,et al.  Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer? , 2016, Bioconjugate chemistry.

[67]  J. Pedraz,et al.  Killing effect of nanoencapsulated colistin sulfate on Pseudomonas aeruginosa from cystic fibrosis patients. , 2016, Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

[68]  A. Mishra,et al.  Targeted theranostic liposomes: rifampicin and ofloxacin loaded pegylated liposomes for theranostic application in mycobacterial infections , 2016 .

[69]  Seong Young Ko,et al.  Active tumor-therapeutic liposomal bacteriobot combining a drug (paclitaxel)-encapsulated liposome with targeting bacteria (Salmonella Typhimurium) , 2016 .

[70]  G. Duman,et al.  Liposome, gel and lipogelosome formulations containing sodium hyaluronate , 2014, Journal of liposome research.

[71]  S. Leroy,et al.  Colistin in multi-drug resistant Pseudomonas aeruginosa blood-stream infections: a narrative review for the clinician. , 2014, The Journal of infection.

[72]  C. Doern,et al.  When Does 2 Plus 2 Equal 5? A Review of Antimicrobial Synergy Testing , 2014, Journal of Clinical Microbiology.

[73]  Mauro Ferrari,et al.  Sustained Zero‐Order Release of Intact Ultra‐Stable Drug‐Loaded Liposomes from an Implantable Nanochannel Delivery System , 2014, Advanced healthcare materials.

[74]  R. Nation,et al.  Interaction of colistin and colistin methanesulfonate with liposomes: colloidal aspects and implications for formulation. , 2012, Journal of pharmaceutical sciences.

[75]  Neang S. Ly,et al.  Resurgence of Colistin: A Review of Resistance, Toxicity, Pharmacodynamics, and Dosing , 2010, Pharmacotherapy.

[76]  Brian T. Tsuji,et al.  Pharmacokinetic/Pharmacodynamic Investigation of Colistin against Pseudomonas aeruginosa Using an In Vitro Model , 2010, Antimicrobial Agents and Chemotherapy.

[77]  J. Li,et al.  Self-assembly behavior of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization. , 2010, The journal of physical chemistry. B.

[78]  J. Li,et al.  Stability of Colistin Methanesulfonate in Pharmaceutical Products and Solutions for Administration to Patients , 2008, Antimicrobial Agents and Chemotherapy.

[79]  N. K. Jain,et al.  Radiolabeling, pharmacoscintigraphic evaluation and antiretroviral efficacy of stavudine loaded 99mTc labeled galactosylated liposomes. , 2008, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[80]  J. Li,et al.  Activity of Colistin against Heteroresistant Acinetobacter baumannii and Emergence of Resistance in an In Vitro Pharmacokinetic/Pharmacodynamic Model , 2007, Antimicrobial Agents and Chemotherapy.

[81]  J. Li,et al.  In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates. , 2007, The Journal of antimicrobial chemotherapy.

[82]  A. M. Carmona-Ribeiro,et al.  Cationic lipids and surfactants as antifungal agents: mode of action. , 2006, The Journal of antimicrobial chemotherapy.

[83]  Phillip J. Bergen,et al.  Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa , 2006, Antimicrobial Agents and Chemotherapy.

[84]  Jian Li,et al.  Pharmacokinetics of Colistin Methanesulfonate and Colistin in a Critically Ill Patient Receiving Continuous Venovenous Hemodiafiltration , 2005, Antimicrobial Agents and Chemotherapy.

[85]  W. Wadsak,et al.  In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[86]  J. Turnidge,et al.  Steady-state pharmacokinetics of intravenous colistin methanesulphonate in patients with cystic fibrosis. , 2003, The Journal of antimicrobial chemotherapy.

[87]  P. Shek,et al.  Enhanced activity of liposomal polymyxin B against Pseudomonas aeruginosa in a rat model of lung infection. , 2002, Biochemical pharmacology.

[88]  J. Turnidge,et al.  In Vitro Pharmacodynamic Properties of Colistin and Colistin Methanesulfonate against Pseudomonas aeruginosaIsolates from Patients with Cystic Fibrosis , 2001, Antimicrobial Agents and Chemotherapy.

[89]  R. Perez-soler,et al.  Development of cationic liposome formulations for intratracheal gene therapy of early lung cancer , 2000, Cancer Gene Therapy.

[90]  W. Oyen,et al.  99mTc-PEG liposomes for the scintigraphic detection of infection and inflammation: clinical evaluation. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[91]  A. Bangham,et al.  Diffusion of univalent ions across the lamellae of swollen phospholipids. , 1965, Journal of molecular biology.

[92]  Z. Burak,et al.  Pre-study on radiolabeling of colistin with Lutetium-177 to develop theranostic infection agent , 2022, Journal of Research in Pharmacy.

[93]  I. Attrée,et al.  Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia. , 2022, Advances in Experimental Medicine and Biology.

[94]  J. Subramony,et al.  Nanoparticle technologies: Recent state of the art and emerging opportunities , 2022, Nanoparticle Therapeutics.

[95]  A. Ozer,et al.  Clinical Applications of Nanosized Drug-Delivery Systems in Lung Cancer Imaging and Therapy. , 2020, Critical reviews in therapeutic drug carrier systems.

[96]  Ajeet Kumar,et al.  Methods for characterization of nanoparticles , 2017 .

[97]  Y. Fong,et al.  Imaging for infection: from visualization of inflammation to visualization of microbes. , 2014, Surgical infections.