Local Drug Delivery Therapy Research Articles

Synthesis of multifunctional superparamagnetic mesoporous ZnMnFe2O4@Fe–CaSiO3 core-shell for medical applications

Herein, we report the synthesis of a mesoporous calcium silicate superparamagnetic nanoparticle as ZnMnFe2O4@Fe–CaSiO3 core-shell. This core-shell nanocomposite reveals excellent properties such as mesoporous nanocomposite, superparamagnetic at room temperature, low toxicity, large surface area, tunable pore size, and easy surface manipulation. The core nanocomposite (ZnMnFe2O4) is synthesized by the hydrothermal method, which shows a superparamagnetic behavior with an excellent saturation magnetization of 52.09 emu/g. The core-shell structure is prepared by a micellar-assisted sol-gel method, which uses a copolymer to create pores in the structure of CaSiO3. To improve the magnetic properties of the core-shell structure, different percent of Fe ions (0%, 5%, and 10%) are doped onto the calcium silicate structure; as for 10% Fe, i.e., ZnMnFe2O4@Fe10–CaSiO3, saturation magnetization and coercive magnetic field are 34.543 emu/g and 1Oe, respectively. In this configuration of nanocomposite, the pore volume and superparamagnetic property increase simultaneously. In addition, the core-shell mesoporous ZnMnFe2O4@Fe–CaSiO3 nanocomposite reveals comparable mesoporous channels (3.4–6 nm), while the amorphous structure of CaSiO3 has not been changed. These core-shell mesoporous superparamagnetic nanocomposites are evaluated in terms of drug loading and release using epirubicin (EPI) as a model drug. It is found that the increase of iron ions improves the capacity to stabilize the pH environment. Additionally, the mesoporous Fe–CaSiO3 nanostructures demonstrate a sustained drug release property that could be used in local drug delivery therapy. Therefore, these mesoporous superparamagnetic nanostructures would be a promising multifunctional platform for local drug delivery, magnetic resonance imaging, magnetic hyperthermia, and bone tissue regeneration.

Engineering a multifunctional 3D-printed PLA-collagen-minocycline-nanoHydroxyapatite scaffold with combined antimicrobial and osteogenic effects for bone regeneration

3D-printing and additive manufacturing can be powerful techniques to design customized structures and produce synthetic bone grafts with multifunctional effects suitable for bone repair. In our work we aimed the development of novel multifunctionalized 3D printed poly(lactic acid) (PLA) scaffolds with bioinspired surface coatings able to reduce bacterial biofilm formation while favoring human bone marrow-derived mesenchymal stem cells (hMSCs) activity. For that purpose, 3D printing was used to prepare PLA scaffolds that were further multifunctionalized with collagen (Col), minocycline (MH) and bioinspired citrate- hydroxyapatite nanoparticles (cHA). PLA-Col-MH-cHA scaffolds provide a closer structural support approximation to native bone architecture with uniform macroporous, adequate wettability and an excellent compressive strength. The addition of MH resulted in an adequate antibiotic release profile that by being compatible with local drug delivery therapy was translated into antibacterial activities against Staphylococcus aureus, a main pathogen associated to bone-related infections. Subsequently, the hMSCs response to these scaffolds revealed that the incorporation of cHA significantly stimulated the adhesion, proliferation and osteogenesis-related gene expression (RUNX2, OCN and OPN) of hMSCs. Furthermore, the association of a bioinspired material (cHA) with the antibiotic MH resulted in a combined effect of an enhanced osteogenic activity. These findings, together with the antibiofilm activity depicted strengthen the appropriateness of this 3D-printed PLA-Col-MH-cHA scaffold for future use in bone repair. By targeting bone repair while mitigating the typical infections associated to bone implants, our 3D scaffolds deliver an integrated strategy with the combined effects further envisaging an increase in the success rate of bone-implanted devices.

Healer Granules in Nonhealing Infected Wounds.

Background:Head-and-neck infection is one of the most frequently encountered issues in the field of oral and maxillofacial surgery. Most of the cases with head-and-neck infections are managed by empirical antibiotic therapy and extraction of offending infected tooth/teeth. However, long-term systemic antibiotic therapy can have profound compromising effects on host immune defense and thereby hamper healing, which, in turn, may lead to life-threatening complications such as localized septic foci or widespread septicemia at times leading to death of an individual. In this study, we are reviewing management of 15 cases with space infection in the maxillofacial region by local drug delivery with the help of collagen particles combined with mupirocin 2% w/w and metronidazole 1% w/w (BioFil-AB). We intend to study its efficacy in managing the space infections associated with extraoral infected wound as well as in preventing hazards of long-term systemic antibiotic therapy.Aims:The aim of this study is to assess the efficacy of the topical use of BioFil-AB in infected maxillofacial wounds.Materials and Methods:A total of 15 patients with infected maxillofacial wounds reporting to the department of oral and maxillofacial surgery were categorized into three groups depending on the severity of infections. Of these 15 cases, 8 patients were suffering from infected extraoral wounds, 3 had traumatic infection, and remaining 4 had extraoral consolidated abscesses due to odontogenic infection. All patients had a history of prior antibiotic therapy. Incision and drainage of the septic focus/foci were performed in most of the cases, and healing of the site was assessed after application of topical BioFil-AB (mupirocin + metronidazole + collagen granules) dressing.Results and Conclusion:Dressing with BioFil-AB granules proved to be efficient in control of infection as well as in promoting uneventful wound healing, especially with good follow-up. Further studies with a large sample size may be necessary to corroborate the findings and provide substantial evidence. This novel local drug delivery therapy will definitely help in maintenance of good host immune response as well as in preventing or minimizing occurrence of antibiotic resistance.

Effects of mesoporous bioglass on physicochemical and biological properties of calcium sulfate bone cements

Bone cement is a promising substitute for bone repair due to its simple operation, excellent plasticity and self-setting after filling bone defect by injection. In this study, calcium sulfate hydrate (CSH)/mesoporous bioglass (MBG) bone cements were prepared through changing the MBG incorporation amount. The ratio of liquid to powder (RLP), mechanical strength, in vitro bioactivity, degradation and cell responses on CSH/MBG cements were investigated. The results showed that appropriate setting times for CSH/MBG cements could be achieved by adjusting the RLP, and the compressive strength was in the range of 5–16MPa. Also, CSH/MBG cements had excellent apatite mineralization ability, and the MBG incorporation could regulate the degradation rate. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on CSH/MBG cements, and the results indicated that CSH/MBG cements stimulated cell proliferation and differentiation. Furthermore, CSH/MBG cements had a sustained drug release property for use in local drug delivery therapy. Hence, CSH/MBG cements have more potential to be bone substitute for bone repair.

Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration

In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ∼170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells’ proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration.

Substitutions of strontium in mesoporous calcium silicate and their physicochemical and biological properties

Calcium silicate (Ca–Si) based bioceramics have been regarded as a potential bioactive materials for bone tissue regeneration. In this study, we have successfully prepared ordered mesoporous strontium (Sr)-substituted CaSiO3 (Sr–CaSiO3) materials by using a triblock copolymer (P123) as a structure-directing agent. The microstructure and porosity of mesoporous Sr–CaSiO3 materials were investigated by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and the N2 adsorption–desorption technique. The substitution of Sr for Ca in mesoporous CaSiO3 did not change the mesoporous structure, but the surface area and pore volume decreased with increasing Sr substitution. The effects of the Sr substitution on the physiochemical and biological properties of mesoporous CaSiO3 materials were evaluated by the ion dissolution, apatite-forming ability, proliferation and alkaline phosphatase (ALP) activity of osteoblast-like MC3T3-E1 cells. The results showed that the increasing Sr substitution decreased the dissolution rate of Ca and Si ions from mesoporous CaSiO3 materials and enhanced the ability to stabilize the pH environment. Mesoporous Sr–CaSiO3 materials have a similar apatite-forming ability to mesoporous CaSiO3 material, and stimulated the proliferation and ALP activity of MC3T3-E1 cells. Furthermore, using gentamicin as a model drug, mesoporous Sr–CaSiO3 materials exhibited a sustained drug release property which could be used in local drug delivery therapy. Furthermore, the drug release rate decreased to some extent with increasing Sr substitution in mesoporous CaSiO3 materials. Therefore, mesoporous Sr–CaSiO3 materials have more potential for application in bone tissue regeneration.

Magnetic mesoporous bioactive glass scaffolds: preparation, physicochemistry and biological properties.

The magnetic 10Fe5Ca MBG scaffolds (Fe3O4-CaO-SiO2-P2O5 system) have been prepared by a combination of polyurethane sponge and P123 as co-templates and an evaporation-induced self-assembly (EISA) process through the substitution of Fe3O4 for CaO in the 15Ca MBG scaffolds (CaO-SiO2-P2O5 system). The structure, magnetic heating, drug release, physicochemical and biological properties were systematically investigated. The results showed that the 10Fe5Ca MBG scaffolds had the interconnected macroporous structure with pore sizes ranging from 200 to 400 μm and the mesoporous wall with a peak pore size of ca. 3.34 nm. Also, the 10Fe5Ca MBG scaffolds exhibited similar mechanical strength, apatite-forming ability and sustained drug release behavior compared to the 15Ca MBG scaffolds. Importantly, the substitution of Fe3O4 for CaO in the MBG scaffolds induced a slower ion dissolution rate and more significant potential to stabilize the pH environment, and facilitated osteoblast cell proliferation, alkaline phosphatase (ALP) activity and osteogenic expression. In particular, the 10Fe5Ca MBG scaffolds could generate heat in an alternating magnetic field. Therefore, the magnetic 10Fe5Ca MBG scaffolds have potential for the regeneration of the critical-size bone defects caused by bone tumors by a combination of magnetic hyperthermia and local drug delivery therapy.

Composition–structure–property relationships of the CaO–MxOy–SiO2–P2O5 (M = Zr, Mg, Sr) mesoporous bioactive glass (MBG) scaffolds

The CaO–MxOy–SiO2–P2O5 (M = Zr, Mg, Sr) MBG scaffolds have been successfully prepared by the combination of polyurethane sponge and block copolymer EO20PO70EO20 (P123) as co-templates and evaporation-induced self-assembly (EISA) process using Ca, P, Si and M sources. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and N2 adsorption–desorption technique were used to analyze the microstructure, pore size and morphology of these MBG scaffolds. These MBG scaffolds have the interconnected macroporous network with the pore diameter of 200–400 μm and the mesoporous wall with the mesopore size of 3–4 nm. The effects of the partial substitution of ZrO2, MgO or SrO for CaO on the physiochemical and biological properties of the MBG scaffolds were evaluated by the mechanical strength, ion dissolution, apatite-forming ability, and proliferation, alkaline phosphatase (ALP) activity and osteogenic expression of osteoblast-like cells MC3T3-E1. The results showed that the ZrO2-substituted MBG scaffold enhanced the mechanical strength, and exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment compared to other MBG scaffolds. The CaO–MxOy–SiO2–P2O5 MBG scaffolds showed a good apatite-forming ability and facilitated osteoblast cells' proliferation and differentiation to different extents. In particular, the ZrO2-substituted MBG scaffold exhibited the best biological property compared to other MBG scaffolds. Furthermore, the CaO–MxOy–SiO2–P2O5 MBG scaffolds also had a sustained drug release property for use in local drug delivery therapy. Therefore, the CaO–MxOy–SiO2–P2O5 MBG scaffolds have more potential for the application in bone tissue regeneration.

ドラッグデリバリー治療へのレーザーホットバルーンの適用:in vitro での基礎的検討

ドラッグデリバリー治療へのレーザーホットバルーンの適用:in vitro での基礎的検討