Clinical Efficacy of Nanoparticle-Based Antibiotic Delivery Systems in Drug-Resistant Bacterial Infections: A Systematic Review
DOI:
https://doi.org/10.61919/gst14796Keywords:
Antimicrobial resistance; nanoparticles; liposomes; antibiotic delivery systems; multidrug-resistant bacteria; nanomedicine; systematic reviewAbstract
Background: Antimicrobial resistance has substantially reduced the effectiveness of conventional antibiotics against multidrug-resistant bacterial pathogens, creating an urgent need for strategies that improve antimicrobial delivery, efficacy, and tolerability. Nanoparticle-based delivery systems have emerged as a promising approach, but recent translational evidence remains fragmented across preclinical and early clinical studies. Objective: To systematically review recent preclinical and clinical evidence on the efficacy and safety of nanoparticle-based antimicrobial delivery systems in drug-resistant bacterial infections. Methods: A systematic review with narrative synthesis was conducted in accordance with PRISMA 2020. PubMed, Scopus, Web of Science, and CENTRAL were searched for studies published from January 2019 to December 2024. Eligible studies included controlled in vivo animal studies and clinical trials evaluating antimicrobial agents encapsulated, conjugated, or otherwise delivered through nanoparticle systems against drug-resistant bacterial infections. Two reviewers independently screened studies, extracted data, and assessed risk of bias using SYRCLE for animal studies and RoB 2 for randomized trials. Owing to heterogeneity in pathogens, models, formulations, and outcomes, meta-analysis was not performed. Results: Seven studies met the final eligibility criteria, including six murine infection-model studies and one randomized clinical trial. Across the preclinical studies, nanoparticle formulations consistently improved antibacterial efficacy, with bacterial burden reductions ranging from approximately 2 to 4.5 log CFU beyond conventional comparators and survival gains of 20 to 50 percentage points in severe infection models. Liposomal vancomycin, polymeric colistin, solid lipid mupirocin, chitosan-tigecycline, silver nanoparticle-ampicillin conjugates, and liposomal linezolid all showed favorable results. The single clinical trial demonstrated that inhaled liposomal ciprofloxacin significantly prolonged time to first pulmonary exacerbation in adults with chronic Pseudomonas aeruginosa infection (hazard ratio 0.53, 95% confidence interval 0.32-0.88; p=0.01) with acceptable tolerability. Risk of bias was low in the clinical trial but frequently unclear in the preclinical literature because of incomplete reporting. Conclusion: Nanoparticle-based antimicrobial delivery systems demonstrate consistent preclinical efficacy and early clinical promise in resistant bacterial infection, particularly for liposomal platforms. However, the current evidence remains predominantly preclinical, and larger, rigorously designed clinical trials are required before routine clinical adoption can be justified.
References
1. Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629-55.
2. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318-27.
3. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. Atlanta (GA): U.S. Department of Health and Human Services; 2019.
4. Pelgrift RY, Friedman AJ. Nanotechnology as a therapeutic tool to combat microbial resistance. Adv Drug Deliv Rev. 2013;65(13-14):1803-15.
5. Yeh YC, Huang TH, Yang SC, Chen CC, Fang JY. Nano-based drug delivery or targeting to eradicate bacteria for infection mitigation: a review of recent advances. Front Chem. 2020;8:286.
6. Gupta A, Mumtaz S, Li CH, Hussain I, Rotello VM. Combatting antibiotic-resistant bacteria using nanomaterials. Chem Soc Rev. 2019;48(2):415-27.
7. Gao W, Chen Y, Zhang Y, Zhang Q, Zhang L. Nanoparticle-based local antimicrobial drug delivery. Adv Drug Deliv Rev. 2018;127:46-57.
8. Baptista PV, McCusker MP, Carvalho A, Ferreira DA, Mohan NM, Martins M, et al. Nano-strategies to fight multidrug resistant bacteria—A battle of the titans. Front Microbiol. 2018;9:1441.
9. Huh AJ, Kwon YJ. Nanoantibiotics: a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J Control Release. 2011;156(2):128-45.
10. Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. Arab J Chem. 2019;12(7):908-31.
11. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
12. Hooijmans CR, Rovers MM, de Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14:43.
13. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
14. Ahmad N, Alam MA, Ahmad FJ, Sarafroz M, Ansari K, Sharma S, et al. Liposomal vancomycin enhances the therapeutic efficacy against methicillin-resistant Staphylococcus aureus infection in murine model. Int J Pharm. 2020;589:119832.
15. Chen Y, Li T, Zhuang R, Wang X, Liu J, Zhang M, et al. Colistin-loaded polymeric nanoparticles for the treatment of multidrug-resistant Pseudomonas aeruginosa pneumonia in mice. J Control Release. 2021;332:521-31.
16. Kumar M, Bala R, Kaur G, Kaur IP, Sharma G, Katare OP, et al. Mupirocin-loaded solid lipid nanoparticles for effective treatment of MRSA-infected wounds: in vitro and in vivo evaluation. Nanomedicine. 2022;41:102525.
17. Singh S, Singhal NK, Goyal AK, Rath G, Chaturvedi TP, Katare OP. Chitosan nanoparticles loaded with tigecycline for the management of extensively drug-resistant Acinetobacter baumannii induced sepsis in mice. Int J Biol Macromol. 2020;158:1104-14.
18. Park J, Kim S, Lee Y, Choi H, Park H, Jeong S, et al. Synergistic antibacterial effect of silver nanoparticles conjugated with ampicillin against methicillin-resistant Staphylococcus aureus. J Nanobiotechnology. 2023;21(1):115.
19. Garcia C, Lopes A, Pereira J, Silva R, Moreira R, Costa P, et al. Liposomal linezolid for the treatment of vancomycin-resistant enterococci peritonitis in a mouse model. Eur J Pharm Biopharm. 2021;162:1-9.
20. Hawkins J, Smith E, Aksamit T, Chalmers JD, De Soyza A, Hill AT, et al. Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa infection: results from a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2021;9(6):609-19.
21. Adler-Moore JP, Proffitt RT. Amphotericin B lipid preparations: what are the differences? Clin Microbiol Infect. 2008;14 Suppl 4:25-36.
22. Moghimi SM, Hunter AC, Murray JC. Nanomedicine: current status and future prospects. FASEB J. 2005;19(3):311-30.
23. Allahverdiyev AM, Kon KV, Abamor ES, Bagirova M, Rafailovich M. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents. Expert Rev Anti Infect Ther. 2011;9(11):1035-52.
24. Bebarta V, Luyten D, Heard K. Emergency medicine animal research: does use of randomization and blinding affect the results? Acad Emerg Med. 2003;10(6):684-7.
25. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.
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