Abstract
In the field of bone regeneration, considerable attention has been addressed towards the use of mesoporous bioactive glasses (MBGs), as multifunctional therapeutic platforms for advanced medical devices. In fact, their extremely high exposed surface area and pore volume allow to load and the release of several drugs, while their framework can be enriched with specific therapeutic ions allowing to boost the tissue regeneration. However, due to the open and easily accessible mesopore structure of MBG, the release of the incorporated therapeutic molecules shows an initial burst effect leading to unsuitable release kinetics. Hence, a still open challenge in the design of drug delivery systems based on MBGs is the control of their release behavior. In this work, Layer-by-layer (LbL) deposition of polyelectrolyte multi-layers was exploited as a powerful and versatile technique for coating the surface of Cu-substituted MBG nanoparticles with innovative multifunctional drug delivery systems for co-releasing of therapeutic copper ions (exerting pro-angiogenic and anti-bacterial effects) and an anti-inflammatory drug (ibuprofen). Two different routes were investigated: in the first strategy, chitosan and alginate were assembled by forming the multi-layered surface, and, successively, ibuprofen was loaded by incipient wetness impregnation, while in the second approach, alginate was replaced by ibuprofen, introduced as polyelectrolyte layer. Zeta-potential, TGA and FT-IR spectroscopy were measured after the addition of each polyelectrolyte layer, confirming the occurrence of the stepwise deposition. In addition, the in vitro bioactivity and the ability to modulate the release of the cargo were evaluated. The polyelectrolyte coated-MBGs were proved to retain the peculiar ability to induce hydroxyapatite formation after 7 days of soaking in Simulated Body Fluid. Both copper ions and ibuprofen were co-released over time, showing a sustained release profile up to 14 days and 24 h, respectively, with a significantly lower burst release compared to the bare MBG particles.
Highlights
This article is an open access articleSince Vallet Regì’s [1] and Zhao’s [2] groups proposed for the first time the use of mesoporous bioactive glasses (MBGs) for biomedical applications, their role in the bone regeneration field [3] and soft tissue applications [4] were extensively studied
Cu-containing MBGs loaded with ibuprofen with the final goal to simultaneously promote angiogenesis, anti-microbial, and anti-inflammatory effects [16] and proved the ability of the resulting system to modulate the ion/drug co-release, avoiding the undesired burst effect, typical of MBGs. Inspired by these promising results, in this contribution, by exploiting the negatively charged surface of the MBG, we investigated the LbL deposition of polyelectrolytes on the surface of Cu-substituted MBG nanoparticles loaded with ibuprofen as an alternative strategy to achieve a sustained co-release of copper ions and drug
The thickness of the multi-layer system is usually evaluated by ellipsometric measurements or Atomic Force Microscopy (AFM) after the deposition on a flat substrate, which allows the homogeneous coating of the surface [43]
Summary
This article is an open access articleSince Vallet Regì’s [1] and Zhao’s [2] groups proposed for the first time the use of mesoporous bioactive glasses (MBGs) for biomedical applications, their role in the bone regeneration field [3] and soft tissue applications [4] were extensively studied. Pharmaceutics 2021, 13, 1952 the ability to store and release therapeutic species exploiting their mesoporous structure Their extremely high exposed surface area and pore volume allow the loading of active agents, such as drugs or growth factors, and their chemical composition can be tailored for specific applications [6,7] through the incorporation of selected metal ions (i.e., Cu, Sr) during the synthesis. By following this strategy, a single biomaterial can be designed and enriched with several therapeutic abilities, spanning from pro-osteogenic [8,9] to proangiogenic or anti-bacterial properties [10]. At variance, sustained drug release from biomaterials could enhance the delivery efficiency, maintaining a suitable therapeutic dose over time directly at the pathological site, reducing, in the meantime, the related side effects
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