Maria Nerantzaki

Modified chitosan coated mesoporous strontium hydroxyapatite nanorods as drug carriers

Mesoporous strontium hydroxyapatite (SrHAp) nanorods (NRs) have been successfully synthesized using a simple and efficient chemical route, i.e. the hydrothermal method. Structural and morphological characterization of the as-synthesized SrHAp NRs have been performed by transmission electron microscopy (TEM) and high angle annular dark field scanning transmission electron microscopy (HAADF-STEM). TEM and HAADF-STEM measurements of the NRs reveal the coexistence of longer and shorter particles with the length ranging from 50 nm to 400 nm and a diameter of about 20-40 nm. Electron tomography measurements of the NRs allow us to better visualize the mesopores and their facets. Two model drugs, hydrophobic risperidone and hydrophilic pramipexole, were loaded into the SrHAp NRs. These nanorods were coated using a modified chitosan (CS) with poly(2-hydroxyethyl methacrylate) (PHEMA), in order to encapsulate the drug-loaded SrHAp nanoparticles and reduce the cytotoxicity of the loaded materials. The drug release from neat and encapsulated SrHAp NRs mainly depends on the drug hydrophilicity. Importantly, although neat SrHAp nanorods exhibit some cytotoxicity against Caco-2 cells, the Cs-g-PHEMA-SrHAp drug-loaded nanorods show an acceptable cytocompatibility.

Use of mesoporous cellular foam (MCF) in preparation of polymeric microspheres for long acting injectable release formulations of paliperidone antipsychotic drug

Graphical abstract Figure. No caption available. ABSTRACT In this study, high surface area mesoporous silica foam with cellular pore morphology (MCF) was used for injectable delivery of paliperidone, an antipsychotic drug used in patients suffering from bipolar disorder. The aim was to enhance paliperidone solubility and simultaneously to prepare long active intractable microspheres. For this reason paliperidone was first loaded in MCF silica, and the whole system was further encapsulated into PLA and PLGA 75/25 w/w copolymer in the form of microspheres. It was found that paliperidone, after its adsorption into MCF, was transformed in its amorphous state, thus leading to enhanced in vitro dissolution profile. Furthermore, incorporation of the drug‐loaded MCF to polymeric microparticles (PLA and PLGA) prolonged the release time of paliperidone from 10 to 15 days.

New N-(2-carboxybenzyl)chitosan composite scaffolds containing nanoTiO2 or bioactive glass with enhanced cell proliferation for bone-tissue engineering applications

ABSTRACT In the present study N-(2-carboxbenzyl)chitosan (CBCS) 3D macroporous hybrid scaffolds with interconnected pore system, containing 0.5, 2.5, and 5 wt% TiO2 nanoparticles (nTiO2) and 2.5 wt% Bioglass 45S5 (BG) have been synthesized using freeze-drying technique. Compressive strength values verified that the modification of chitosan combined with the presence of inorganic fillers can attribute significant mechanical stiffness to the scaffold. The in vitro biomineralization test confirmed that all samples were bioinert as mineral deposits were detected with X-ray diffractometry after incubation in SBF. Cytotoxicity and biocompatibility of all scaffolds were tested by using and Wharton’s jelly–derived mesenchymal stem cells (WJ-MSCs) and human embryonic kidney 293 (HEK 293) cell line. Metabolic activity, proliferation, migration, and attachment to the scaffolds were examined. Cells appeared to attach around the superficial pores and migrate in them. Cells also maintained their morphology, proliferated, and migrated across the scaffolds and showed consistent and proved compatibility. GRAPHICAL ABSTRACT

PLGA/SBA-15 mesoporous silica composite microparticles loaded with paclitaxel for local chemotherapy

Abstract In this work, high surface area mesoporous silica (SBA‐15) was loaded with paclitaxel (taxol, PTX) and was further entrapped into poly(lactic acid‐co‐glycolic acid) (PLGA) microparticles (MPs). A modified solvent evaporation‐emulsion method was used in order to formulate the composite microparticles with sizes of 8–12 &mgr;m. PTX loaded SBA‐15 as well as the PLGA/PTX‐SBA‐15 composites were characterized in terms of their morphology, crystal structure and thermal properties. Drug content, loading efficiency, particle size and the in‐vitro drug release kinetics of the PLGA/PTX‐SBA‐15 microspheres were also investigated. The in vitro release studies were carried out using Simulated Body Fluid (SBF) at 37 °C revealing that the prepared formulations present higher dissolution rate than pure PTX and sustained pattern which is ideal for anticancer carriers. Modeling and data analysis of the in vitro drug release was also investigated. It was also shown that all microparticles have low cytotoxicity in HUVE cells. Finally, it was found that drug loaded microparticles are very effective in Human Cervical Adenocarcinoma (HeLa) cells.

Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5–10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer–Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.

Design of a Multifunctional Nanoengineered PLLA Surface by Maximizing the Synergies between Biochemical and Surface Design Bactericidal Effects

Nanotechnology, the manipulation of matter on atomic, molecular, and supramolecular scales, has become the most appealing strategy for biomedical applications and is of great interest as an approach to preventing microbial risks. In this study, we utilize the antimicrobial performance and the drug-loading ability of novel nanoparticles based on silicon oxide and strontium-substituted hydroxyapatite to develop nanocomposite antimicrobial films based on a poly(l-lactic acid) (PLLA) polymer. We also demonstrate that nanoimprint lithography (NIL), a process adaptable to industrial application, is a feasible fabrication technique to modify the surface of PLLA, to alter its physical properties, and to utilize it for antibacterial applications. Various nanocomposite PLLA films with nanosized (black silicon) and three-dimensional (hierarchical) hybrid domains were fabricated by thermal NIL, and their bactericidal activity against Escherichia coli and Staphylococcus aureus was assessed. Our findings demonstrate that besides hydrophobicity the nanoparticle antibiotic delivery and the surface roughness are essential factors that affect the biofilm formation.