Study on Doxorubicin Loading on Differently Functionalized Iron Oxide Nanoparticles: Implications for Controlled Drug-Delivery Application.

Nanoplatforms applied for the loading of anticancer drugs is a cutting-edge approach for drug delivery to tumors and reduction of toxic effects on healthy cells. In this study, we describe the synthesis and compare the sorption properties of four types of potential doxorubicin-carriers, in which iron oxide nanoparticles (IONs) are functionalized with cationic (polyethylenimine, PEI), anionic (polystyrenesulfonate, PSS), and nonionic (dextran) polymers, as well as with porous carbon. The IONs are thoroughly characterized by X-ray diffraction, IR spectroscopy, high resolution TEM (HRTEM), SEM, magnetic susceptibility, and the zeta-potential measurements in the pH range of 3-10. The degree of doxorubicin loading at pH 7.4, as well as the degree of desorption at pH 5.0, distinctive to cancerous tumor environment, are measured. Particles modified with PEI were shown to exhibit the highest loading capacity, while the greatest release at pH 5 (up to 30%) occurs from the surface of magnetite decorated with PSS. Such a slow release of the drug would imply a prolonged tumor-inhibiting action on the affected tissue or organ. Assessment of the toxicity (using Neuro2A cell line) for PEI- and PSS-modified IONs showed no negative effect. In conclusion, the preliminary evaluation of the effects of IONs coated with PSS and PEI on the rate of blood clotting was carried out. The results obtained can be taken into account when developing new drug delivery platforms.

CaCO3-based carriers with prolonged release properties for antifungal drug delivery to hair follicles.

Superficial fungal infections are of serious concern worldwide due to their morbidity and increasing distribution across the globe in this era of growing antimicrobial resistance. The delivery of antifungals to the target regions of the skin and sustaining the effective drug concentration are essential for successful treatment of such mycoses. Topical formulations get extra benefits here if they penetrate into the hair follicles since fungal hyphae can proliferate and produce spores in such reservoirs. We designed a novel particulate system for the encapsulation and intrafollicular delivery of griseofulvin (Gf) antifungal drug, which is water-insoluble and currently commercially available in oral dosage forms. Micron-sized calcium carbonate (vaterite) carriers containing 25 ± 3% (w/w) of Gf were prepared via the wet chemical method. The successful in vivo transportation of the carriers into the hair follicles of rats was demonstrated using scanning electron and confocal laser scanning microscopy. In addition, we introduced an approach toward Gf release prolongation for the proposed system. The stabilizing coatings were formed on the surface of the obtained particles via the layer-by-layer technique. The formulations displayed sufficient biocompatibility and good cellular uptake in contact with fibroblast cells in vitro. Four different coatings were tested for their preserving ability in the course of continued carrier incubation in the model media. The best release prolonging formulation liberated 38% of the loaded Gf during 5 days, while the uncoated carriers demonstrated more than 50% drug release within the first 24 h in water. To assess the in vivo release properties, free Gf drug and Gf-loaded carriers (uncovered and covered with the stabilizing shell) were administered topically in rats and the drug excretion profiles were further studied. By comparing the daily Gf levels in urine, we verified the sustained effect (longer than a week) of the stabilizing shell formed on the carrier surface. Conversely, the application of the free drug did not provide reliable Gf detection for this period. These findings open new prospects for the efficiency enhancement of topical therapeutics. Importantly, the elaborated system could be adapted for the dermal delivery of various water-insoluble drugs beyond the scope of antifungal therapy.

A simple assay for probing transformations of superparamagnetic iron oxide nanoparticles in human serum.

A novel approach for monitoring the biomolecular interactions of superparamagnetic nanoparticles was disclosed. Based on ultrafiltration of a human serum-nanoparticle mixture and the mass spectrometric analysis of filtrates, this assay revealed for iron oxide nanoparticles coated with poly(acrylic acid) satisfactory biopersistence and a bimodal binding to sulfur-containing biomolecules, with the formation of the protein corona completed in about 1 h.

Characterization of the protein corona of gold nanoparticles by an advanced treatment of CE-ICP-MS data.

CE is well known not only as an efficient separation method, but also as a viable tool for studying chemical reactions, including kinetic assaying and analysis of chemical equilibria. In this communication, the latter feature of CE interfaced with ICP-MS was exploited to determine the stoichiometric composition of the protein corona of gold nanoparticles (AuNPs) at equilibrium conditions. For both individual albumin and human serum involved in binding, the number of protein molecules bound per AuNP (n) was calculated. Since the time scale of the corona formation was previously found to be dependent on the particle size, two calculation algorithms were adopted here. In the case of 5-nm AuNPs, rather slowly associating with the protein, the peak areas measured for the conjugated and free particles were taken in computation (the (34) S signal due to bound protein was also monitored simultaneously to confirm that equilibrium is reached). In binding labile systems (10-50 nm AuNPs), the particles are converted into the protein-bound form relatively fast due mostly to the favor of a much greater excess of the protein so that no peak of the free particles interacting with serum being recorded. Therefore, the n value was estimated by relating the sulfur peak area of each of these conjugates to that of 5-nm AuNPs to calculate the number of bound albumin molecules that was then divided by the number of AuNPs. The AuNPs were found to react with from 13 to 292 albumin molecules that is in good agreement with the literature data.

Preconcentration and fluorimetric determination of polycyclic aromatic hydrocarbons based on the acid-induced cloud-point extraction with sodium dodecylsulfate.

The acid-induced cloud-point extraction (CPE) technique based on sodium dodecylsulfate (SDS) micelles has been used for preconcentration of ten representatives of polycyclic aromatic hydrocarbons (PAHs) for the following fluorescence determination. The effect of the acidity of solution, SDS and electrolyte concentrations, centrifugation time and rate on the two-phase separation process and extraction percentages of PAHs have systematically been examined. Extraction percentages have been obtained for all PAHs after CPE ranged from 67 to 93%. Pyrene was used as a fluorescent probe to monitor the micropolarity of the surfactant-rich phase compared with SDS micelles and this allows one to conclude that water content in micellar phase after CPE is reduced. The spectral, metrological and analytical characteristics of PAH fluorimetric determination after acid-based CPE with sodium dodecylsulfate are presented. Advantages provided by using CPE in combination with fluorimetric determination of PAHs are discussed. The determination of benz[a]pyrene in tap water is presented as an example.