Demineralized bone matrix paste formulated with biomimetic PLGA microcarriers for the vancomycin hydrochloride controlled delivery: Release profile, citotoxicity and efficacy against S. aureus

Marco Govoni, Erwin P Lamparelli, Maria C Ciardulli, Antonietta Santoro, Antonio Oliviero, Ida Palazzo, Ernesto Reverchon, Leonardo Vivarelli, Alessandra Maso, Elisa Storni, Maria E Donati, Gianluca Ruspaggiari, Nicola Maffulli, Milena Fini, Giovanna Della Porta, Dante Dallari

Research output: Contribution to journalArticlepeer-review

Abstract

Infection and resulting bone defects caused by Staphylococcus aureus is one of the major issues in orthopaedic surgeries. Vancomycin hydrochloride (VaH) is largely used to manage these events. Here, a human derived bone paste supplemented with biopolymer microcarriers for VaH sustained delivery to merge osteoinductive and antimicrobial actions is described. In detail, different emulsion formulations were tested to fabricate micro-carriers of poly-lactic-co-glycolic acid (PLGA) and hydroxyapatite (HA) by a proprietary technology (named Supercritical Emulsion Extraction). These carriers (mean size 827 ± 68 μm; loading 47 mgVaH/gPLGA) were assembled with human demineralized bone matrix (DBM) to obtain an antimicrobial bone paste system (250 mg/0.5 cm3 w/v, carrier/DBM). Release profiles in PBS indicated a daily drug average release of about 4 µg/mL over two weeks. This concentration was close to the minimum inhibitory concentration and able to effectively inhibit the S. aureus growth in our experimental sets. Carriers cytotoxicity tests showed absence of adverse effects on cell viability at the concentrations used for paste assembly. This approach points toward the potential of the DBM-carrier-antibiotic system in hampering the bacterial growth with accurately controlled antibiotic release and opens perspectives on functional bone paste with PLGA carriers for the controlled release of bioactive molecules.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume582
DOIs
Publication statusPublished - May 30 2020

Keywords

  • Controlled delivery
  • Cytotoxicity
  • Demineralized bone matrix
  • PLGA microcarrier
  • Staphylococcus aureus
  • Vancomycin hydrochloride

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