Daptomycin-loaded biodegradable thermosensitive hydrogels enhance drug stability and foster bactericidal activity against Staphylococcus aureus

Cristina Casadidio; Maria Eugenia Butini; Andrej Trampuz; Mariagrazia Di Luca; Roberta Censi; Piera Di Martino

doi:10.1016/j.ejpb.2018.07.001

Daptomycin-loaded biodegradable thermosensitive hydrogels enhance drug stability and foster bactericidal activity against Staphylococcus aureus

Cristina Casadidio, Maria Eugenia Butini, Andrej Trampuz, Mariagrazia Di Luca, Roberta Censi^*, Piera Di Martino

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

A drug delivery system based on fully biodegradable thermosensitive hydrogels enabling controlled antibiotic release may support the management of implant-associated infections. In this work, the lipopeptide antibiotic daptomycin was encapsulated in hydrogel networks consisting of vinyl sulfonated triblock copolymers of PEG-p(HPMAm-lac_1,2) and thiolated hyaluronic acid. High concentrations of active daptomycin exceeding the minimum biofilm eradicating concentration were sustainably eluted from the biodegradable carrier. The drug release profiles were tailored by varying the degree of substitution (DS) of thiol groups of hyaluronic acid, reaching a plateau level after 200 and 330 h for DS values of 53% and 31%, respectively. The hydrogel polymeric network preserved the structural stability of the loaded antibiotic and retained the calcium-dependent daptomycin activity, showing a noticeable biofilm bactericidal effect against a 24 h-old Staphylococcus aureus biofilm in vitro. The two-component thermosensitive hydrogels demonstrated to be an excellent antibiotic releasing scaffold with potential clinical applications in the management of implant-associated infections.

Original language	English
Pages (from-to)	260-271
Number of pages	12
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	130
DOIs	https://doi.org/10.1016/j.ejpb.2018.07.001
Publication status	Published - 1 Sept 2018

Funding

Authors acknowledge receipt of funding from the European Commission of a H2020-MSCA-ITN-2015 award through the project ISPIC (grant number 675743 ) and a H2020-MSCA-RISE-2016 award through the project CHARMED (grant number 734684 ). An educational grant was also provided by the PRO-IMPLANT Foundation (Berlin, Germany). Authors also acknowledge Manuela Cortese for her support in performing HPLC-MS analyses, Dimitrios Agas and Maria Giovanna Sabbieti for helping in the experimental design and Anna Koliszak for her contribution in isothermal microcalorimetric experiments.

Keywords

Antibiotic controlled release
Daptomycin
Implant-associated infections
Staphylococcal biofilm
Thermosensitive hydrogels

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10.1016/j.ejpb.2018.07.001

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title = "Daptomycin-loaded biodegradable thermosensitive hydrogels enhance drug stability and foster bactericidal activity against Staphylococcus aureus",

abstract = "A drug delivery system based on fully biodegradable thermosensitive hydrogels enabling controlled antibiotic release may support the management of implant-associated infections. In this work, the lipopeptide antibiotic daptomycin was encapsulated in hydrogel networks consisting of vinyl sulfonated triblock copolymers of PEG-p(HPMAm-lac1,2) and thiolated hyaluronic acid. High concentrations of active daptomycin exceeding the minimum biofilm eradicating concentration were sustainably eluted from the biodegradable carrier. The drug release profiles were tailored by varying the degree of substitution (DS) of thiol groups of hyaluronic acid, reaching a plateau level after 200 and 330 h for DS values of 53% and 31%, respectively. The hydrogel polymeric network preserved the structural stability of the loaded antibiotic and retained the calcium-dependent daptomycin activity, showing a noticeable biofilm bactericidal effect against a 24 h-old Staphylococcus aureus biofilm in vitro. The two-component thermosensitive hydrogels demonstrated to be an excellent antibiotic releasing scaffold with potential clinical applications in the management of implant-associated infections.",

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author = "Cristina Casadidio and Butini, {Maria Eugenia} and Andrej Trampuz and {Di Luca}, Mariagrazia and Roberta Censi and {Di Martino}, Piera",

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doi = "10.1016/j.ejpb.2018.07.001",

language = "English",

volume = "130",

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Daptomycin-loaded biodegradable thermosensitive hydrogels enhance drug stability and foster bactericidal activity against Staphylococcus aureus. / Casadidio, Cristina; Butini, Maria Eugenia; Trampuz, Andrej et al.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 130, 01.09.2018, p. 260-271.

Research output: Contribution to journal › Article › Academic › peer-review

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AU - Censi, Roberta

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Daptomycin-loaded biodegradable thermosensitive hydrogels enhance drug stability and foster bactericidal activity against Staphylococcus aureus

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