Sustained Release of Antibacterial Lipopeptides from Biodegradable Polymers against Oral Pathogens.
The development of antibacterial drugs to overcome various pathogenic species, which inhabit the oral cavity, faces several challenges, such as salivary flow and enzymatic activity that restrict dosage retention. Owing to their amphipathic nature, antimicrobial peptides (AMPs) serve as the first line of defense of the innate immune system. The ability to synthesize different types of AMPs enables exploitation of their advantages as alternatives to antibiotics. Sustained release of AMPs incorporated in biodegradable polymers can be advantageous in maintaining high levels of the peptides. In this study, four potent ultra-short lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO) and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained release. The lipopeptide and polymer formulations were tested for antibacterial activity during one week, by turbidometric measurements of bacterial outgrowth, anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and XTT colorimetric assays, mode of action by fluorescence-activated cell sorting (FACS) and release profile by a fluorometric assay. The results show that an antibacterial and anti-biofilm effect, as well as membrane disruption, can be achieved by the use of a formulation of lipopeptide incorporated in biodegradable polymer.
Department of Prosthodontics, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Lea H
LH
Eckhard
Department of Prosthodontics, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Yael
Y
Houri-Haddad
Institute of Dental Science, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Asaf
A
Sol
Department of Prosthodontics, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Rotem
R
Zeharia
Department of Biological Chemistry, the Weizmann Institute of Science, Rehovot, Israel.
Yechiel
Y
Shai
Orthopedic Surgery Department, Hadassah Medical Center, Jerusalem, Israel.
Shaul
S
Beyth
Institute for Drug Research, School of Pharmacology, Faculty of Medicine, the Hebrew University, Jerusalem, Israel.
Abraham J
AJ
Domb
Institute of Dental Science, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Gilad
G
Bachrach
Department of Prosthodontics, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Nurit
N
Beyth
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry*; D018441:Biofilms / Q000187:drug effects; D002368:Castor Oil / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003124:Colorimetry; D003692:Delayed-Action Preparations; D006461:Hemolysis / Q000187:drug effects; D007700:Kinetics; D019344:Lactic Acid / Q000494:pharmacology; D055666:Lipopeptides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000187:drug effects / Q000382:microbiology*; D011108:Polymers / Q000737:chemistry*; D012756:Sheep
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D055666:Lipopeptides; D011108:Polymers; D019344:Lactic Acid; D002368:Castor Oil