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. 2021 Nov 2;13(11):1840. doi: 10.3390/pharmaceutics13111840

Table 3.

AMP-encapsulated nanogels applicable for treatment of various bacterial infections.

Type of Nanoparticles and Particle Composition AMP Physicochemical Properties (Size, Surface Charge, Encapsulation Efficiency, Release) In Vitro/In Vivo Results Application Refs.
Natural cationic polymer-based
Chitosan: tripolyphosphate Temporin B 185 nm, +8.8 mV, up to 75% EE, burst effect + gradual release (17% over 15 days)
  • -

    Increased antibacterial activity and sustained antibacterial action against various strains of S. epidermidis for 4 days *

  • -

    Reduced cytotoxicity towards mouse embryo fibroblasts *

 Topical infections [123]
Chitosan Pep-H 244 nm, +12 mV, 72% EE, 30% burst release, up to 50% released over 72 h
  • -

    H-CSNPs increased efficacy of Pep-H against intracellular M. tuberculosis at 5–10 times lower concentration *

 Intracellular infections [125]
Chitosan: tripolyphosphate Cryptdin-2 105 nm, −22 mV, 60% EE and 65% in vitro release in 4.5 h
  • -

    Mice infected with S. enterica showed 83% survivability compared to 100% mortality in peptide treated animals

 Intestinal infections [124]
Chitosan and poly-γ-glutamic acid LL-37 793–2128 nm, −36 to +50 mV,
23–76% EE, 90% released in 10 h		 N/A Infections [121]
2,3-Dimethyl maleic
anhydride grafted chito-oligosaccharide		 Polymyxin B 154 nm, −8.7 mV
  • -

    Maintained antimicrobial efficacy towards P. aeruginosa and E. coli and reduced cytotoxicity *

  • -

    Increased safety in vivo *

 Systemic infections [141]
Natural anionic polymer-based
Alginate Polymyxin B 100–125 nm, −7 to −35 mV, ~90% EE
  • -

    Comparable induction of carboxyfluorescein leakage from bacterial mimicking DOPE/DOPG liposomes *

 Infections [142]
Alginate Pep19–2.5 342–841 nm, released in pancreatic fluid in 1 h
  • -

    Maintained inhibition of cytokine induction *

 Gastrointestinal infections [127]
Octenyl succinic anhydride-modified HA Novicidin 80–144 nm, −24 to −57 mV, 15–71% EE
Complete release over 12 days
  • -

    Antimicrobial activity maintained towards S. aureus and E. coli *

  • -

    Significantly reduced cytotoxicity for HUVEC and NIH3T3 cells *

 Systemic infections [130]
Octenyl succinic anhydride-modified HA DJK-5 174–194 nm, −11.6 to −9.5 mV, 33–60% EE, complete release in 48 h
  • -

    Maintained bactericidal in vivo in P. aeruginosa skin infection *

  • -

    Significantly reduced toxicity after systemic/subcutaneous administration *

 Systemic or topical infections [19]
Octenyl succinic anhydride-modified HA LBP-3 155–250 nm, −10 to −28 mV, 37–90% EE
  • -

    Improved P. aeruginosa killing kinetics *

  • -

    Decreased cytotoxicity to liver cells *

 Systemic or pulmonary infections [129]
Poly-L-lysine cross-linked HA Vancomycin
GFP		 120 nm, −15.4 to −35 mV, DL of 4%, complete release in 48 h
  • -

    Internalized by lung cells

  • -

    Improved antimicrobial activity towards P. aeruginosa, E. coli, A. baumannii, S. enterica and S. aureus *

 Intracellular of pulmonary infections [131]
Oleyamine-modified HA Vancomycin 201–360 nm, −17.6 to −20.4 mV, 26–43% EE, drug release over 72 h
  • -

    4-fold lower MIC towards S. aureus and MRSA *

  • -

    Increased impact on MRSA membrane *

 Infections [143]
11-Amino-1-undecanethiol hydrochloride-modified HA LLKKK18 533 nm, +2.4 mV, approx. 70% EE
  • -

    Internalized by macrophages

  • -

    Colocalized with M. tuberculosis and M. avium within host cells

 Intracellular infections [132]
PEG-poly(glutamic acid) MSI-78 80–120 nm, −16 to −38 mV, 75–87% EE, approx. 80% released in 4 days
  • -

    Reduced hemolysis *

  • -

    Antimicrobial activity E. coli, B. subtilis and S. aureus not affected *

 Systemic infections [144]
Synthetic polymer-based
Poly (styrene sulfonate) Polymyxin B 166–186 nm, −40 mV, approx. 80% released
  • -

    Increasing antimicrobial activity towards P. aeruginosa with increasing polymyxin B concentration

 Infections [145]
PAA-g-PNIPAAm polyelectrolyte complex E5 N/A
  • -

    E5 peptide in PAA-g-PNIPAAm induced liposome leakage *

  • -

    More significant leakage at 35 °C than 25 °C

 Infections [139]
PEG20K-hbG3-OH dendritic nanogels DPK-060
LL-37		 205–331 nm, −5 to +5 mV, 40–60 μM/0.1 wt %
  • -

    Maintained membrane destabilizing activity *

  • -

    Reduced cytotoxicity towards erythrocytes *

  • -

    Maintained antimicrobial activity towards E. coli *

 Systemic or topical infections [146]
Poly(ethyl acrylate-co-methacrylic acid) microgels DPK-060
LL-37		 50–260 nm, −10 to −30 mV, 35–75% peptide released in 2 h
  • -

    Low cytotoxicity towards erythrocytes *

  • -

    Bacterial-mimicking membrane disruption mediated almost exclusively by peptide release

 Systemic infections [140]
Poly (EA/MAA/BDDA) microgels EFK17 N/A size, −30 mV, 60–100% release in 1 h
  • -

    Antimicrobial activity towards E. coli maintained *

 Infections [147]

Acronyms: AMP = antimicrobial peptide, EA/MAA/BDDA = ethyl acrylate/methacrylic acid/1,4-butandiol diacrylate, GFP = Green fluorescent protein, HA = hyaluronic acid, MIC = minimum inhibitory concentration, PAA-g-PNIPAAm = PAA main chain and thermoresponsive poly(N-isopropylacrylamide) graft chains, PEG = polyethylene glycol; * compared to peptide solution.