Sporopollenin Capsules as Biomimetic Templates for the Synthesis of Hydroxyapatite and ß-TCP.

Pollen grains, with their resilient sporopollenin exine and defined morphologies, have been explored as bio-templates for the synthesis of calcium phosphate minerals, particularly hydroxyapatite (HAp) and ß-tricalcium phosphate (TCP). Various pollen morphologies from different plant species (black alder, dandelion, lamb's quarters, ragweed, and stargazer lily) were evaluated. Pollen grains underwent acid washing to remove allergenic material and facilitate subsequent calcification. Ragweed and lamb's quarter pollen grains were chosen as templates for calcium phosphate salts deposition due to their distinct morphologies. The calcification process yielded well-defined spherical hollow particles. The washing step, intended to reduce the protein content, did not significantly affect the final product; thus, justifying the removal of this low-yield step from the synthesis process. Characterisation techniques, including X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, and thermal gravimetric analysis, confirmed the successful calcification of pollen-derived materials, revealing that calcified grains were principally composed of calcium deficient HAp. After calcination, biphasic calcium phosphate composed of HAp and TPC was obtained. This study demonstrated the feasibility of using pollen grains as green and sustainable bio-templates for synthesizing biomaterials with controlled morphology, showcasing their potential in biomedical applications such as drug delivery and bone regeneration.

A Six-Year Hydration Evaluation of Cs-Bearing Materials at Room Temperature and 55% Relative Humidity Simulating Radioactive Waste with Different Crystallinities.

Radioactive wastes often contain amorphous and crystalline phases, and vapor hydration can affect their durability. In this study, Cs-clinoptilolite was heated (at 1100 °C and for 2-36 h) to prepare the samples that were composed mainly of an amorphous phase (AmP) and CsAlSi5O12 (≥94%) with minor CsAlSi2O6. Six samples with an AmP/CsAlSi5O12 ratio from 26.5 to 0.1 were kept at 21 °C and 55% relative humidity, and their hydration was measured via thermogravimetry (TG) over a period of almost six years. The hydration that resulted was directly related to the AmP quantity. The increase in water content followed a logarithmic trend over time. It reached 1.95% in the AmP-richest material, while it attained only 0.07% in the most crystalline sample. The hydrolysis of the AmP led to an increase over time in the tightly bound water. Samples with an AmP of ≤19% demonstrated slightly higher durability due to the lower Cs content in the AmP.

Surfactant-Free Chitosan/Cellulose Acetate Phthalate Nanoparticles: An Attempt to Solve the Needs of Captopril Administration in Paediatrics.

The Paediatric Committee of the European Medicines Agency encourages research into medicinal products for children, in particular, the development of an age-appropriate formulation of captopril is required in the cardiovascular therapeutic area. The aim of this study was the development of a liquid formulation using nanoparticles based only on chitosan and cellulose acetate phthalate containing captopril for the treatment of hypertension, heart failure and diabetic nephropathy in paediatric patients. Nanoparticles were prepared by a nanoprecipitation method/dropping technique without using surfactants, whose use can be associated with toxicity. A range of different cellulose to chitosan weight ratios were tested. A good encapsulation efficiency (61.0 ± 6.5%) was obtained when a high chitosan concentration was used (1:3 ratio); these nanoparticles (named NP-C) were spherical with a mean diameter of 427.1 ± 32.7 nm, 0.17 ± 0.09 PDI and +53.30 ± 0.95 mV zeta potential. NP-C dispersion remained stable for 28 days in terms of size and drug content and no captopril degradation was observed. NP-C dispersion released 70% of captopril after 2 h in pH 7.4 phosphate buffer and NP-C dispersion did not have a cytotoxicity effect on neonatal human fibroblasts except at the highest dose tested after 48 h. As a result, chitosan/cellulose nanoparticles could be considered a suitable platform for captopril delivery in paediatrics for preparing solid/liquid dosage forms.

Antibacterial activity of Zn-loaded Cuban zeolite against Helicobacter pylori in comparison to its Na-loaded and unmodified counterparts.

Helicobacter pylori can be found in the stomach of about half of the humans, and a large population can be associated with serious diseases. To survive in the stomach H. pylori increases the pH locally by producing ammonia which binds to H+ becoming ammonium. This work investigated the effects on the in-vitro growth of H. pylori of a natural cation-exchanger mainly composed (≈70%) of clinoptilolite and mordenite. The zeolitized material from Cuba was evaluated in its original form (M), as well as in its Na- (M-Na) and Zn-exchanged (M-Zn) counterparts. In the preliminary agar cup diffusion test, H. pylori revealed susceptibility only to M-Zn, with a direct relationship between concentration and width of inhibition halo. Further experiments evidenced that bacterium replication increases when ammonium is supplied to the growth medium and decreases when zeolites subtract NH4+ via ion exchange. Due to the multi-cationic population of its zeolites M was not effective enough in removing ammonium and, in the Minimum Inhibitory Concentration (MIC) test, allowed bacterial growth even at a concentration of 50 mg/mL. Inhibition was achieved with M-Na because it contained sodium zeolites capable of maximizing NH4+ subtraction, although the MIC was high (30 mg/mL). M-Zn evidenced a more effective inhibitory capacity, with a MIC of 4 mg/mL. Zinc has antimicrobial properties and H. pylori growth was affected by Zn2+ released from clinoptilolite and mordenite. These zeolites, being more selective towards NH4+ than Zn2+, can also subtract ammonium to the bacterium, thus enhancing the efficacy of M-Zn.

Evaluation of Antibacterial and Cytotoxicity Properties of Silver Nanowires and Their Composites with Carbon Nanotubes for Biomedical Applications.

In this work, we prepared silver nanowires (AgNWs) via the polyol method in the presence or absence of single wall carbon nanotubes (CNTs) and tested their physicochemical, antibacterial and cytotoxic properties. Results showed that the introduction of CNTs lead to the formation of AgNWs at lower temperature, but the final product characteristics of AgNWs and AgNWs-CNT were not significantly different. AgNWs exhibited antibacterial properties against all the studied bacterial species via the formation of oxygen reactive species (ROS) and membrane damage. Furthermore, AgNWs exhibited a dose-dependent and time-dependent toxicity at concentrations ≥ 10 µg/mL. Fibroblasts appeared to be more resistant than human colorectal adenocarcinoma (Caco-2) and osteoblasts to the toxicity of AgNWs. The cytotoxicity of AgNWs was found to be related to the formation of ROS, but not to membrane damage. Overall, these results suggest that AgNWs are potential antibacterial agents against E. coli, S. aureus, MRSA and S. saprophyticus, but their dosage needs to be adjusted according to the route of administration.

Sustained Release from Injectable Composite Gels Loaded with Silver Nanowires Designed to Combat Bacterial Resistance in Bone Regeneration Applications.

One-dimensional nanostructures, such as silver nanowires (AgNWs), have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties. However, their application in the prevention of infections linked to bone tissue regeneration intervention has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag⁺ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension, and able to completely prevent biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as they present enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into the potential clinical applications of these materials.

Aqueous injection of quercetin: An approach for confirmation of its direct in vivo cardiovascular effects.

Potential positive effects of flavonol quercetin on humans were suggested by many studies. However, it is not clear if these effects are mediated by quercetin or its metabolites. The in vivo confirmation of quercetin effects is largely hindered by its low water solubility and thus impossibility to test directly its impact. Therefore, a solid dispersion of quercetin with polyvinylpyrrolidone (PVP) was developed to prepare an injectable formulation of water-soluble quercetin. The optimized formulation provided a 20,000-fold increase in quercetin solubility. This formulation was tested on conventional and spontaneously hypertensive rats; it lowered their blood pressure in both short- and long-term basis. Pharmacokinetic data are also provided. This study reports for the first time an injectable water-soluble formulation of quercetin suitable for confirmation of its vascular effect in vivo.

The effect of formulative parameters on the size and physical stability of SLN based on "green" components.

Cocoa butter (CB) is a largely used excipient in pharmaceutical field. Aim of this work was to set formulative parameters for the preparation of SLN based on "green" lipid matrix for drug delivery as natural, both human and environmental safe systems. Double emulsion technique (w1/o/w2) was selected for SLN preparation. The effect on the dimensional properties of different surfactants (Tween 80 and PEG 40 monostearate) and co-surfactants (PEG400 monostearate, Emulium® Kappa2 and Plurol®Stearique) at different concentrations was evaluated. Stability tests were performed. SLN dispersions were exsiccated and the effect of the dried process on SLN size was evaluated. The influence of temperature on SLN dimensions was investigated at 37 °C. MTT test was performed on raw materials and formulations. The w1/o/w2 is suitable, rapid and economic technique for the preparation of CB SLN. Tween 80-Plurol Stearique combination gives the best results: particles size less than 400 nm and PI of about 0.4 are obtained when PS 2% is used. Both raw materials and formulations are safe. The importance to evaluate the effect of different surfactant and/or co-surfactant on the dimensional properties of SLN is evident by selecting substances with preferable safety profiles, and favorable environmental properties to develop stable "green" SLN.

Solid microparticles based on chitosan or methyl-ß-cyclodextrin: a first formulative approach to increase the nose-to-brain transport of deferoxamine mesylate.

We propose the formulation and characterization of solid microparticles as nasal drug delivery systems able to increase the nose-to-brain transport of deferoxamine mesylate (DFO), a neuroprotector unable to cross the blood brain barrier and inducing negative peripheral impacts. Spherical chitosan chloride and methyl-ß-cyclodextrin microparticles loaded with DFO (DCH and MCD, respectively) were obtained by spray drying. Their volume-surface diameters ranged from 1.77 ± 0.06 µm (DCH) to 3.47 ± 0.05 µm (MCD); the aerodynamic diameters were about 1.1 µm and their drug content was about 30%. In comparison with DCH, MCD enhanced the in vitro DFO permeation across lipophilic membranes, similarly as shown by ex vivo permeation studies across porcine nasal mucosa. Moreover, MCD were able to promote the DFO permeation across monolayers of PC 12 cells (neuron-like), but like DCH, it did not modify the DFO permeation pattern across Caco-2 monolayers (epithelial-like). Nasal administration to rats of 200 µg DFO encapsulated in the microparticles resulted in its uptake into the cerebrospinal fluid (CSF) with peak values ranging from 3.83 ± 0.68 µg/mL (DCH) to 14.37 ± 1.69 µg/mL (MCD) 30 min after insufflation of microparticles. No drug CSF uptake was detected after nasal administration of a DFO water solution. The DFO systemic absolute bioavailabilities obtained by DCH and MCD nasal administration were 6% and 15%, respectively. Chitosan chloride and methyl-ß-cyclodextrins appear therefore suitable to formulate solid microparticles able to promote the nose to brain uptake of DFO and to limit its systemic exposure.

Development of solid nanoparticles based on hydroxypropyl-ß-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium.

OBJECTIVES: Nanoparticles were designed for the oral administration and transmucosal colon delivery of drugs. METHODS: Preparation parameters were studied in order to develop solid pH-dependent drug-release nanoparticles, constituted by hydroxypropyl-ß-cyclodextrin and/or Eudragit(®) L100 loaded with diclofenac sodium. Nanoemulsions were prepared by the emulsion-evaporation method using various homogenizers. Different preparative conditions were tested. The emulsions obtained were analysed in terms of size and then dried to obtain solid nanoparticles which were characterized in vitro (particle size, morphology, dissolution, solid state characterization). The effect of nanoparticles on drug permeation through synthetic membranes, colonic pig mucosa and Caco2 cell line were performed. Toxicity studies were carried out to assess the safety of the raw materials used and the nanosystems produced. KEY FINDINGS: Appropriate parameters to obtain nanoemulsions stable enough to be desiccated were determined: Panda NS100L was the most suitable homogenizer for the preparation; particle size ranged between 100 and 600 nm depending on the production method. Solid nanoparticles were obtained by an exsiccation process, which does not modify the mean size. pH-dependent drug-release nanoparticles were obtained. The nanoencapsulation process decreased the crystallinity of the drug. Materials and nanoparticles were highly biocompatible. Transmucosal delivery of drug is dependent on the polymer and the test employed: cyclodextrin improved drug permeation across colonic pig mucosa. CONCLUSIONS: Formulations containing hydroxypropyl-ß-cyclodextrin represent new colon-targeted nanoparticles for transmucosal delivery of drugs.