Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection

Andrea Fulgione; Nunzia Nocerino; Marco Iannaccone; Sante Roperto; Federico Capuano; Norberto Roveri; Marco Lelli; Antonio Crasto; Armando Calogero; Argenia Paola Pilloni; Rosanna Capparelli

doi:10.1371/journal.pone.0158646

Lactoferrin Adsorbed onto Biomimetic Hydroxyapatite Nanocrystals Controlling - In Vivo - the Helicobacter pylori Infection

PLoS One. 2016 Jul 6;11(7):e0158646. doi: 10.1371/journal.pone.0158646. eCollection 2016.

Affiliations

¹ Department of Agriculture, University of Naples "Federico II", Portici (Naples), Italy.
² Department of Veterinary Medicine and Animal Productions, Division of Infectious Diseases, University of Naples "Federico II", Naples, Italy.
³ Department of Food Inspection, Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici (Naples), Italy.
⁴ Department of Chemistry "G. Ciamician", Alma Mater Studiorum, University of Bologna, LEBSC, Bologna, Italy.
⁵ Advanced Biomedical Science Department, University of Naples "Federico II", Naples, Italy.
⁶ Department of Experimental Medicine, Division of Clinical Bacteriology, Second University of Naples, Naples, Italy.

Abstract

Background: The resistance of Helicobacter pylori to the antibiotic therapy poses the problem to discover new therapeutic approaches. Recently it has been stated that antibacterial, immunomodulatory, and antioxidant properties of lactoferrin are increased when this protein is surface-linked to biomimetic hydroxyapatite nanocrystals.

Objective: Based on these knowledge, the aim of the study was to investigate the efficacy of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles with cell free supernatant from probiotic Lactobacillus paracasei as an alternative therapy against Helicobacter pylori infection.

Methods: Antibacterial and antinflammatory properties, humoral antibody induction, histopathological analysis and absence of side effects were evaluated in both in vitro and in vivo studies.

Results: The tests carried out have been demonstrated better performance of lactoferrin delivered by biomimetic hydroxyapatite nanoparticles combined with cell free supernatant from probiotic Lactobacillus paracasei compared to both lactoferrin and probiotic alone or pooled.

Conclusion: These findings indicate the effectiveness and safety of our proposed therapy as alternative treatment for Helicobacter pylori infection.

MeSH terms

Adsorption
Animals
Anti-Infective Agents / administration & dosage
Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacology
Biomimetic Materials / chemistry
Culture Media, Conditioned / pharmacology
Cytokines / metabolism
Drug Delivery Systems / methods
Durapatite / chemistry*
Gastric Mucosa / metabolism
Helicobacter Infections / microbiology*
Helicobacter Infections / prevention & control
Helicobacter pylori / drug effects
Helicobacter pylori / physiology*
Host-Pathogen Interactions / drug effects
Lacticaseibacillus paracasei / physiology
Lactoferrin / administration & dosage
Lactoferrin / chemistry*
Lactoferrin / pharmacology
Mice, Inbred BALB C
Microscopy, Electron, Transmission
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Probiotics / administration & dosage
Probiotics / pharmacology
Stomach / drug effects
Stomach / microbiology
Treatment Outcome
X-Ray Diffraction

Substances

Anti-Infective Agents
Culture Media, Conditioned
Cytokines
Durapatite
Lactoferrin

Grants and funding

Funded by RBAP114AMK, RINAME Project (funds for selected research topics), the Interuniversity Consortium for Research on Chemistry of Metals in Biological Systems, Qualifu project, Chemical Center Srl and P.O.R. Campania F.S.E. 2007/2013 (Percorsi universitari finalizzati alla incentivazione della ricerca scientifica, dell'innovazione e del trasferimento tecnologico - Tipologia progettuale: “Dottorati in Azienda” CUP E65E12000150006) for financial support. Dr. Marco Iannaccone was supported by research funding from “Fondazione con il Sud” (Project no.2011-PDR-18, “Biosensori piezoelettrici a risposta in tempo reale per applicazioni ambientali e agro-alimentari”).