April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Antimicrobial Activity of a Cathelicidin Derivative Conjugated to Polymerized-Liposomes
Author Affiliations & Notes
  • S. Kolar
    University of Houston College of Optometry, Houston, Texas
  • A. Kumar
    Department of Chemistry, University of Houston, Houston, Texas
  • C. Cai
    Department of Chemistry, University of Houston, Houston, Texas
  • A. M. McDermott
    University of Houston College of Optometry, Houston, Texas
  • Footnotes
    Commercial Relationships  S. Kolar, None; A. Kumar, None; C. Cai, None; A.M. McDermott, None.
  • Footnotes
    Support  NSF DMR-0706627, IBIS, EY07751, AOF
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 431. doi:
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      S. Kolar, A. Kumar, C. Cai, A. M. McDermott; Antimicrobial Activity of a Cathelicidin Derivative Conjugated to Polymerized-Liposomes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):431.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Human antimicrobial-peptides (AMPs) are novel bioactive-molecules that are effective despite the emergence of multidrug-resistant pathogens. Therefore, they serve as potential alternatives to traditional-antibiotics. However, very high doses are needed for in-vivo activity which can be associated with cytotoxicity. In an attempt to improve their efficacy and minimize toxicity, a polyvalent presentation tethering AMPs to the surface of polymerized-liposomes was tested.

Methods: : Cathelicidin derivative LL-25 was conjugated onto polymerized-liposomes (10,12- pentacosadiynoic-acid) via covalent bonding using copper-assisted click reaction or cabodiimide-coupling reaction or via non-covalent immobilization through electrostatic-interactions on anionic surfaces. Pseudomonas aeruginosa (PA01) were incubated with 0 µg/ml - 1 mg/ml of LL-25 conjugated-liposomes or 50 µg/ml LL-25 as control for 2h at 37°C. Samples were plated and colony-forming-units counted after overnight incubation. The amount of LL-25 incorporated into the liposomes was quantified by measuring the amino-groups using Fluorescamine.

Results: : The amount of LL-25 incorporated per mg/ml of liposome was 310, 80 and 20 µg/ml using the click, electrostatic and carbodiimide methods respectively. Unconjugated-liposomes did not cause bacterial killing whereas all three forms of the LL-25 modified liposomes caused concentration dependent killing ranging from 4% to 100%. When expressed relative to the antibacterial activity of LL-25 alone, click-modified conjugates demonstrated 72 fold greater activity whereas that for electrostatic and carbodiimide conjugates was 137 and 1304 fold lower respectively (n= 2-3 experiments). However, as conjugation via carbodiimide-coupling involves reaction of amine with carboxylic-acid, the amount incorporated by carbodiimide-coupling is an underestimate thus the activity relative to LL-25 is also artificially low.

Conclusions: : This study demonstrates that click-reaction provides for high-efficiency conjugation of AMPs onto polymerized-liposomes which results in a high local AMP concentration and enhanced antimicrobial efficacy. Thus, AMPs have significant potential as novel antibiotics for clinical use.

Keywords: antibiotics/antifungals/antiparasitics • drug toxicity/drug effects • bacterial disease 

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