PMID- 28790818
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20190113
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 12
DP  - 2017
TI  - Peptide-modified nanoparticles inhibit formation of Porphyromonas gingivalis 
      biofilms with Streptococcus gordonii.
PG  - 4553-4562
LID - 10.2147/IJN.S139178 [doi]
AB  - PURPOSE: The interaction of Porphyromonas gingivalis with commensal streptococci 
      promotes P. gingivalis colonization of the oral cavity. We previously showed that 
      a synthetic peptide (BAR) derived from Streptococcus gordonii potently inhibited 
      the formation of P. gingivalis/S. gordonii biofilms (IC(50) =1.3 microM) and reduced 
      P. gingivalis virulence in a mouse model of periodontitis. Thus, BAR represents a 
      novel therapeutic to control periodontitis by limiting P. gingivalis colonization 
      of the oral cavity. Here, we sought to develop drug-delivery vehicles for 
      potential use in the oral cavity that comprise BAR-modified 
      poly(lactic-co-glycolic)acid (PLGA) nanoparticles (NPs). METHODS: PLGA-NPs were 
      initially modified with palmitylated avidin and subsequently conjugated with 
      biotinylated BAR. The extent of BAR modification was quantified using a 
      fluorescent-labeled peptide. Inhibition of P. gingivalis adherence to S. gordonii 
      by BAR-modified NPs was compared with free peptide using a two-species biofilm 
      model. RESULTS: BAR-modified NPs exhibited an average size of 99+/-29 nm and a more 
      positive surface charge than unmodified NPs (zeta potentials of -7 mV and -25 mV, 
      respectively). Binding saturation occurred when 37 nmol BAR/mg of avidin-NPs was 
      used, which resulted in a payload of 7.42 nmol BAR/mg NPs. BAR-modified NPs bound 
      to P. gingivalis in a dose-dependent manner and more potently inhibited P. 
      gingivalis/S. gordonii adherence and biofilm formation relative to an equimolar 
      amount of free peptide (IC(50) of 0.2 microM versus 1.3 microM). BAR-modified NPs also 
      disrupted the preformed P. gingivalis/S. gordonii biofilms more effectively than 
      free peptide. Finally, we demonstrate that BAR-modified NPs promoted multivalent 
      association with P. gingivalis, providing an explanation for the increased 
      effectiveness of NPs. CONCLUSION: These results indicate that BAR-modified NPs 
      deliver a higher local dose of peptide and may represent a more effective 
      therapeutic approach to limit P. gingivalis colonization of the oral cavity 
      compared to treatment with formulations of free peptide.
FAU - Kalia, Paridhi
AU  - Kalia P
AD  - Department of Oral Immunology and Infectious Diseases, University of Louisville 
      School of Dentistry.
FAU - Jain, Ankita
AU  - Jain A
AD  - Department of Oral Immunology and Infectious Diseases, University of Louisville 
      School of Dentistry.
FAU - Radha Krishnan, Ranjith
AU  - Radha Krishnan R
AD  - Department of Oral Immunology and Infectious Diseases, University of Louisville 
      School of Dentistry.
FAU - Demuth, Donald R
AU  - Demuth DR
AD  - Department of Oral Immunology and Infectious Diseases, University of Louisville 
      School of Dentistry.
AD  - Department of Microbiology and Immunology, University of Louisville School of 
      Medicine.
FAU - Steinbach-Rankins, Jill M
AU  - Steinbach-Rankins JM
AD  - Department of Microbiology and Immunology, University of Louisville School of 
      Medicine.
AD  - Department of Bioengineering, University of Louisville Speed School of 
      Engineering.
AD  - Department of Pharmacology and Toxicology, University of Louisville School of 
      Medicine.
AD  - Center for Predictive Medicine, University of Louisville, Louisville, KY, USA.
LA  - eng
GR  - R01 DE023206/DE/NIDCR NIH HHS/United States
GR  - R21 DE025345/DE/NIDCR NIH HHS/United States
PT  - Journal Article
DEP - 20170622
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Peptides)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Anti-Bacterial Agents/administration & dosage/chemistry/*pharmacology
MH  - Bacterial Adhesion/drug effects
MH  - Bacterial Proteins/chemistry
MH  - Biofilms/drug effects
MH  - Drug Delivery Systems/methods
MH  - Lactic Acid/chemistry
MH  - Nanoparticles/administration & dosage/*chemistry
MH  - Peptides/chemistry/*pharmacology
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Porphyromonas gingivalis/*drug effects/physiology
MH  - Streptococcus gordonii/*chemistry/drug effects
PMC - PMC5488760
OTO - NOTNLM
OT  - Porphyromonas gingivalis
OT  - drug delivery
OT  - multivalent
OT  - nanoparticle
OT  - peptide delivery
OT  - periodontal disease
COIS- Disclosure The authors report no conflicts of interest in this work.
EDAT- 2017/08/10 06:00
MHDA- 2017/10/31 06:00
PMCR- 2017/06/22
CRDT- 2017/08/10 06:00
PHST- 2017/08/10 06:00 [entrez]
PHST- 2017/08/10 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
PHST- 2017/06/22 00:00 [pmc-release]
AID - ijn-12-4553 [pii]
AID - 10.2147/IJN.S139178 [doi]
PST - epublish
SO  - Int J Nanomedicine. 2017 Jun 22;12:4553-4562. doi: 10.2147/IJN.S139178. 
      eCollection 2017.