Polymeric Nanoparticulate Delivery Vehicles of Antimicrobials for Biofilm Eradication

  • Yuezhou Zhang
  • Luofeng Yu
  • Jianhong Zhang
  • Peng LiEmail author


Given the challenge that the number of existing antibiotic resistant strains and species is increasing at an alarming rate, in particular these biofilm-associated microorganisms are often thought to be hard to eradicate by free antibiotics since they are embedded in a condensed polymeric matrix therefore hamper the effective killing. The develoment of nanotechnology enable the deeper penetration and targeting of antibiotics to noramlly unreached biofilm. Combined with the diversity of polymers, antibiotics has been formulated into different version of delivery vehicles with antimicrobials included to deplete biofilm. In addition, polymeric nanocomposite can also be assembled by incorporating other type of toxic nanoparticles to achieve synergetic biofilm eradication outcomes.


Biofilm Eradication Polymeric nanoparticles Delivery vehicles Antimicrobials Tolerance 



This research was supported by the Fundamental Research Funds for the Central Universities of China, grant number 31020190QD030, the National Key R&D Program of China (2018YFC1105402 and 2017YFA0207202).


  1. 1.
    Ladavière C, Gref R (2015) Toward an optimized treatment of intracellular bacterial infections: input of nanoparticulate drug delivery systems. Nanomedicine 10(19):3033–3055CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lu HD, Yang SS, Wilson BK, McManus SA, Chen CV-H, Prud’homme RK (2017) Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens. Appl Nanosci 7(3–4):83–93CrossRefGoogle Scholar
  3. 3.
    Ma X, Zhang Y, Weisensee K (2019) Conducting polymeric nanocomposites with a three-dimensional co-flow microfluidics platform. Micromachines 10(6):383CrossRefGoogle Scholar
  4. 4.
    Khan H, Sakharkar M, Nayak A, Kishore U, Khan A (2018) Nanoparticles for biomedical applications: an overview. In: Nanobiomaterials. Elsevier, pp 357–384Google Scholar
  5. 5.
    Zhang Y, Tu J, Wang D, Zhu H, Maity SK, Qu X, Bogaert B, Pei H, Zhang H (2018) Programmable and multifunctional DNA-based materials for biomedical applications. Adv Mater 30(2):e1703658CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Patel S, Singh D, Srivastava S, Singh M, Shah K, Chauahn DN, Chauhan NS (2017) Nanoparticles as a platform for antimicrobial drug delivery. Adv Pharmacol Pharm 5(3):31–43Google Scholar
  7. 7.
    Baptista PV, McCusker MP, Carvalho A, Ferreira DA, Mohan NM, Martins M, Fernandes AR (2018) Nano-strategies to fight multidrug resistant Bacteria—“a battle of the titans”. Front Microbiol 9:1441CrossRefGoogle Scholar
  8. 8.
    Biswaro LS, Sousa MGdC, Rezende TMB, Dias SC, Franco OL (2018) Antimicrobial peptides and nanotechnology, recent advances and challenges. Front Microbiol 9:855CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gao W, Thamphiwatana S, Angsantikul P, Zhang L (2014) Nanoparticle approaches against bacterial infections. Wiley Interdiscip Rev Nanomed Nanobiotechnol 6(6):532–547CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Anderson GG, Palermo JJ, Schilling JD, Roth R, Heuser J, Hultgren SJ (2003) Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301(5629):105–107CrossRefPubMedGoogle Scholar
  11. 11.
    Niemira BA, Solomon EB (2005) Sensitivity of planktonic and biofilm-associated Salmonella spp. to ionizing radiation. Appl Environ Microbiol 71(5):2732–2736CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK (2016) Extracellular matrix structure. Adv Drug Deliv Rev 97:4–27CrossRefPubMedGoogle Scholar
  13. 13.
    Ikuma K, Decho AW, Lau BL (2015) When nanoparticles meet biofilms—interactions guiding the environmental fate and accumulation of nanoparticles. Front Microbiol 6:591CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Liu Y, Shi L, Su L, van der Mei HC, Jutte PC, Ren Y, Busscher HJ (2019) Nanotechnology-based antimicrobials and delivery systems for biofilm-infection control. Chem Soc Rev 48:428–446CrossRefGoogle Scholar
  15. 15.
    Ramos MADS, Silva PBD, Spósito L, Toledo LGD, Bonifácio BV, Rodero CF, Santos KCD, Chorilli M, Bauab TM (2018) Nanotechnology-based drug delivery systems for control of microbial biofilms: a review. Int J Nanomedicine 13:1179–1213CrossRefGoogle Scholar
  16. 16.
    Forier K, Raemdonck K, Smedt SCD, Demeester J, Coenye T, Braeckmans KJJoCR (2014) Lipid and polymer nanoparticles for drug delivery to bacterial biofilms. J Control Release 190:607–623CrossRefPubMedGoogle Scholar
  17. 17.
    Lam SJ, Wong EH, Boyer C, Qiao GG (2018) Antimicrobial polymeric nanoparticles. Prog Polym Sci 76:40–64CrossRefGoogle Scholar
  18. 18.
    Alexandra Muñoz-Bonilla MF-G (2012) Polymeric materials with antimicrobial activity. Prog Polym Sci 37(2):281–339CrossRefGoogle Scholar
  19. 19.
    Nguyen TK, Lam SJ, Ho KK, Kumar N, Qiao GG, Egan S, Boyer C, Wong EH (2017) Rational design of single-chain polymeric nanoparticles that kill planktonic and biofilm bacteria. ACS Infect Dis 3(3):237–248CrossRefPubMedGoogle Scholar
  20. 20.
    Li J, Zhang K, Ruan L, Chin SF, Wickramasinghe N, Liu H, Ravikumar V, Ren J, Duan H, Yang L (2018) Block copolymer nanoparticles remove biofilms of drug-resistant Gram-positive bacteria by nanoscale bacterial debridement. Nano Lett 18(7):4180–4187CrossRefPubMedGoogle Scholar
  21. 21.
    Takahashi C, Ogawa N, Kawashima Y, Yamamoto HJM (2015) Observation of antibacterial effect of biodegradable polymeric nanoparticles on Staphylococcus epidermidis biofilm using FE-SEM with an ionic liquid. Microscopy 64(3):169–180CrossRefPubMedGoogle Scholar
  22. 22.
    Gupta A, Landis RF, Li C-H, Schnurr M, Das R, Lee Y-W, Yazdani M, Liu Y, Kozlova A, Rotello VM (2018) Engineered polymer nanoparticles with unprecedented antimicrobial efficacy and therapeutic indices against multidrug-resistant bacteria and biofilms. J Am Chem Soc 140(38):12137–12143CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ajf D, Santos CG, Gündel SS, Roggia I, Raffin RP, Ourique AF, Rcv S, Gomes P (2017) Anti biofilm effect of dihydromyricetin-loaded nanocapsules on urinary catheter infected by Pseudomonas aeruginosa. Colloids Surf B Biointerfaces 156:282–291CrossRefGoogle Scholar
  24. 24.
    Priyadarshini M, Antipina MN, Fawzy A (2018) Formulation and characterization of poly (lactic-co-glycolic acid) encapsulated clove oil nanoparticles for dental applications. IET Nanobiotechnol 12(3):311–317CrossRefGoogle Scholar
  25. 25.
    Ivanova A, Ivanova K, Hoyo J, Heinze T, Sanchez-Gomez S, Tzanov T (2018) Layer-by-layer decorated nanoparticles with tunable antibacterial and antibiofilm properties against both gram-positive and Gram-negative bacteria. ACS Appl Mater Interfaces 10(4):3314–3323CrossRefPubMedGoogle Scholar
  26. 26.
    Okshevsky M, Regina VR, Meyer RL (2015) Extracellular DNA as a target for biofilm control. Curr Opin Biotechnol 33:73–80CrossRefPubMedGoogle Scholar
  27. 27.
    Baelo A, Levato R, Julián E, Crespo A, Astola J, Gavaldà J, Engel E, Mateos-Timoneda MA, Torrents E (2015) Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections. J Control Release 209:150–158CrossRefPubMedGoogle Scholar
  28. 28.
    Tan Y, Ma S, Leonhard M, Moser D, Haselmann GM, Wang J, Eder D, Schneider-Stickler B (2018) Enhancing antibiofilm activity with functional chitosan nanoparticles targeting biofilm cells and biofilm matrix. Carbohydr Polym 200:35–42CrossRefPubMedGoogle Scholar
  29. 29.
    Xi W, Deng A, Cao W, Qiang L, Wang L, Jie Z, Hu B, Xing X (2018) Synthesis of chitosan/poly (ethylene glycol)-modified magnetic nanoparticles for antibiotic delivery and their enhanced anti-biofilm activity in the presence of magnetic field. J Mater Sci 53(9):1–17Google Scholar
  30. 30.
    Benjamin H, Klein MI, Geelsu H, Yong L, Dongyeop K, Hyun K, Benoit DSW (2015) pH-activated nanoparticles for controlled topical delivery of farnesol to disrupt oral biofilm virulence. ACS Nano 9(3):2390–2404CrossRefGoogle Scholar
  31. 31.
    Mahmoud MY, Demuth DR, Steinbach-Rankins JM (2018) BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis—Streptococcus gordonii biofilms. J Nanobiotechnol 16(1):69CrossRefGoogle Scholar
  32. 32.
    Baek J-S, Tan CH, Ng NKJ, Yeo YP, Rice SA, Loo SCJ (2018) A programmable lipid-polymer hybrid nanoparticle system for localized, sustained antibiotic delivery to Gram-positive and Gram-negative bacterial biofilms. Nanoscale Horiz 3(3):305–311CrossRefGoogle Scholar
  33. 33.
    Yong L, Mei HCVD, Zhao B, Yan Z, Cheng T, Li Y, Zhang Z, Busscher HJ, Ren Y, Shi L (2017) Eradication of multidrug-resistant staphylococcal infections by light-activatable micellar nanocarriers in a murine model. Adv Funct Mater 27(44):1701974CrossRefGoogle Scholar
  34. 34.
    Liu Y, Busscher HJ, Zhao B, Li Y, Zhang Z, Hc VDM, Ren Y, Shi L (2016) Surface-adaptive, antimicrobially loaded, micellar nanocarriers with enhanced penetration and killing efficiency in staphylococcal biofilms. ACS Nano 10(4):4779–4789CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Liu Y, Ren Y, Li Y, Su L, Zhang Y, Huang F, Liu J, Liu J, van Kooten TG, An Y (2018) Nanocarriers with conjugated antimicrobials to eradicate pathogenic biofilms evaluated in murine in vivo and human ex vivo infection models. Acta Biomater 79:331–343CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Zhan YO, Shu JG, Yi YY (2013) Short synthetic β-sheet forming peptide amphiphiles as broad spectrum antimicrobials with antibiofilm and endotoxin neutralizing capabilities. Adv Funct Mater 23(29):3682–3692CrossRefGoogle Scholar
  37. 37.
    Gao Y, Wang J, Hu D, Deng Y, Chen T, Jin Q, Ji J (2018) Bacteria-targeted supramolecular photosensitizer delivery vehicles for photodynamic ablation against biofilms. Macromol Rapid Commun 40:e1800763CrossRefGoogle Scholar
  38. 38.
    Elzoghby AO, Samy WM, Elgindy NA (2012) Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Release 157(2):168–182CrossRefGoogle Scholar
  39. 39.
    Goswami S, Thiyagarajan D, Das G, Ramesh A (2014) Biocompatible nanocarrier fortified with a dipyridinium-based amphiphile for eradication of biofilm. ACS Appl Mater Interfaces 6(18):16384–16394CrossRefGoogle Scholar
  40. 40.
    Lillehoj H, Liu Y, Calsamiglia S, Fernandez-Miyakawa ME, Fang C, Cravens RL, Oh S, Gay CG (2018) Phytochemicals as antibiotic alternatives to promote growth and enhance host health. Vet Res 49(1):76CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Singh S, Verma D, Mirza MA, Das AK, Dudeja M, Anwer MK, Sultana Y, Talegaonkar S, Iqbal Z (2017) Development and optimization of ketoconazole loaded nano-transfersomal gel for vaginal delivery using box-Behnken design: in vitro, ex vivo characterization and antimicrobial evaluation. J Drug Delivery Sci Technol 39:95–103CrossRefGoogle Scholar
  42. 42.
    Landis RF, Li CH, Gupta A, Lee YW, Yazdani M, Ngernyuang N, Altinbasak I, Mansoor S, Khichi MAS, Sanyal A (2018) Biodegradable nanocomposite antimicrobials for the eradication of multidrug-resistant bacterial biofilms without accumulated resistance. J Am Chem Soc 140(19):6176–6182CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Li S, Dong S, Xu W, Tu S, Yan L, Zhao C, Ding J, Chen X (2018) Antibacterial hydrogels. Adv Sci 5(5):1700527CrossRefGoogle Scholar
  44. 44.
    Markowska K, Grudniak AM, Wolska KI (2013) Silver nanoparticles as an alternative strategy against bacterial biofilms. Acta Biochim Pol 60(4):523–530PubMedGoogle Scholar
  45. 45.
    Martinez-Gutierrez F, Boegli L, Agostinho A, Sánchez EM, Bach H, Ruiz F, James G (2013) Anti-biofilm activity of silver nanoparticles against different microorganisms. Biofouling 29(6):651–660CrossRefPubMedGoogle Scholar
  46. 46.
    Wu J, Hou S, Ren D, Mather PT (2009) Antimicrobial properties of nanostructured hydrogel webs containing silver. Biomacromolecules 10(9):2686–2693CrossRefPubMedGoogle Scholar
  47. 47.
    Ferrer MCC, Dastgheyb S, Hickok NJ, Eckmann DM, Composto RJ (2014) Designing nanogel carriers for antibacterial applications. Acta Biomater 10(5):2105–2111CrossRefPubMedCentralGoogle Scholar
  48. 48.
    Mujahid M, Ahmad L, Ahmad M (2017) Synthesis of ZnO nanogel for the treatment of superficial skin microbial infections. J Drug Delivery Ther 7(2):58–61CrossRefGoogle Scholar
  49. 49.
    Zhang Y, Zhang J, Chen M, Gong H, Thamphiwatana S, Eckmann L, Gao W, Zhang L (2016) A bioadhesive nanoparticle–hydrogel hybrid system for localized antimicrobial drug delivery. ACS Appl Mater Interfaces 8(28):18367–18374CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Kłodzińska SN, Molchanova N, Franzyk H, Hansen PR, Damborg P, Nielsen HM (2018) Biopolymer nanogels improve antibacterial activity and safety profile of a novel lysine-based α-peptide/β-peptoid peptidomimetic. Eur J Pharm Biopharm 128:1–9CrossRefPubMedGoogle Scholar
  51. 51.
    Abraham T, Mao M, Tan C (2018) Engineering approaches of smart, bio-inspired vesicles for biomedical applications. Phys Biol 15(6):061001CrossRefPubMedGoogle Scholar
  52. 52.
    Lee JS, Feijen J (2012) Polymersomes for drug delivery: design, formation and characterization. J Control Release 161(2):473–483CrossRefPubMedGoogle Scholar
  53. 53.
    Geilich BM, van de Ven AL, Singleton GL, Sepúlveda LJ, Sridhar S, Webster TJ (2015) Silver nanoparticle-embedded polymersome nanocarriers for the treatment of antibiotic-resistant infections. Nanoscale 7(8):3511–3519CrossRefPubMedGoogle Scholar
  54. 54.
    Geilich BM, Gelfat I, Sridhar S, Ven ALVD, Webster TJ (2017) Superparamagnetic iron oxide-encapsulating polymersome nanocarriers for biofilm eradication. Biomaterials 119:78CrossRefPubMedGoogle Scholar
  55. 55.
    Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4(2):145–160CrossRefGoogle Scholar
  56. 56.
    Rukavina Z, Vanić Ž (2016) Current trends in development of liposomes for targeting bacterial biofilms. Pharmaceutics 8(2):18CrossRefPubMedCentralGoogle Scholar
  57. 57.
    Munaweera I, Shaikh S, Maples D, Nigatu AS, Sethuraman SN, Ranjan A, Greenberg DE, Chopra R (2018) Temperature-sensitive liposomal ciprofloxacin for the treatment of biofilm on infected metal implants using alternating magnetic fields. Int J Hyperth 34(2):189–200CrossRefGoogle Scholar
  58. 58.
    Sun LM, Zhang CL, Li P (2012) Characterization, antibiofilm, and mechanism of action of novel PEG-stabilized lipid nanoparticles loaded with terpinen-4-ol. J Agric Food Chem 60(24):6150CrossRefPubMedGoogle Scholar
  59. 59.
    Dong D, Thomas N, Thierry B, Vreugde S, Prestidge CA, Wormald PJ (2015) Distribution and inhibition of liposomes on Staphylococcus aureus and Pseudomonas aeruginosa biofilm. PLoS One 10(6):e0131806CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Tucker N, Stanger J, Staiger M, Razzaq H, Hofman K (2012) The history of the science and technology of electrospinning from 1600 to 1995. J Eng Fibers Fabr 7:63–73Google Scholar
  61. 61.
    Vasantha VA, Rahim SZZ, Jayaraman S, Junyuan GH, Puniredd SR, Ramakrishna S, Teo SL-M, Parthiban A (2016) Antibacterial, electrospun nanofibers of novel poly (sulfobetaine) and poly (sulfabetaine) s. J Mater Chem B 4(15):2731–2738CrossRefGoogle Scholar
  62. 62.
    Ahire JJ, Hattingh M, Neveling DP, Dicks LM (2016) Copper-containing anti-biofilm nanofiber scaffolds as a wound dressing material. PLoS One 11(3):e0152755CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Alharbi HF, Luqman M, Fouad H, Khalil KA, Alharthi NH (2018) Viscoelastic behavior of core-shell structured nanofibers of PLA and PVA produced by coaxial electrospinning. Polym Test 67:136CrossRefGoogle Scholar
  64. 64.
    Alharbi HF, Luqman M, Khan ST (2018) Antibiofilm activity of synthesized electrospun core-shell nanofiber composites of PLA and PVA with silver nanoparticles. Mater Res Express 5(9):095001CrossRefGoogle Scholar
  65. 65.
    López-Esparza J, Espinosa-Cristóbal LnF, Donohue-Cornejo A, Reyes-López SnY (2016) Antimicrobial activity of silver nanoparticles in polycaprolactone nanofibers against gram-positive and gram-negative bacteria. Ind Eng Chem Res 55(49):12532–12538CrossRefGoogle Scholar
  66. 66.
    Ahire JJ, Neveling DP, Hattingh M, Dicks LM (2015) Ciprofloxacin-eluting nanofibers inhibits biofilm formation by Pseudomonas aeruginosa and a methicillin-resistant Staphylococcus aureus. PLoS One 10(4):e0123648CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Ashbaugh AG, Jiang X, Zheng J, Tsai AS, Kim W-S, Thompson JM, Miller RJ, Shahbazian JH, Wang Y, Dillen CA (2016) Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo. Proc Natl Acad Sci 113(45):E6919–E6928CrossRefPubMedGoogle Scholar
  68. 68.
    Wolfmeier H, Pletzer D, Mansour SC, Rew H (2018) New perspectives in biofilm eradication. ACS Infect Dis 4(2):93–106CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Álvarez-Paino M, Muñoz-Bonilla A, Fernández-García M (2017) Antimicrobial polymers in the nano-world. Nano 7(2):48Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Yuezhou Zhang
    • 1
  • Luofeng Yu
    • 2
  • Jianhong Zhang
    • 1
  • Peng Li
    • 1
    Email author
  1. 1.Xi’an Institute of Flexible Electronics & Xi’an Institute of Biomedical Materials and Engineering, Northwestern Polytechnical University (NPU)Xi’anChina
  2. 2.Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM)Nanjing Tech University (NanjingTech)NanjingChina

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