Gelatin-Zinc Carrier as a New Method of Targeted and Controlled Release of Risedronate.

The essence of drug delivery is to use an appropriate carrier that delivers the active substance to the appropriate pathogenic site at a specific time. This study aims to develop a novel drug carrier characterized by the controlled and targeted release of risedronate (RSD). The search for new routes to deliver RSD is important because oral delivery has many disadvantages. The carrier proposed in this work is composed of gelatin, polyphosphates, and zinc. The zinc contained in the carrier is responsible for coordinating the drug. The resulting material releases RSD in a controlled manner. The rate of delivery of the substance to the body depends on the pH of the environment. This study investigated the delivery of RSD in a neutral environment, where the process exhibited a prolonged and consistent release rate. This process has also been studied in an acidic environment, which accelerates the release of the drug. Mixed-environment studies were also conducted. Initially, the drug was released in a neutral environment, and then the conditions rapidly changed to acidic. In this case, the carrier demonstrated high stability and controlled release, adapting the rate of drug release to the prevailing environmental conditions. The presented results indicate the great potential of the new gelatin-based carrier in the delivery of risedronate.

Zeolites with Divalent Ions as Carriers in the Delivery of Epigallocatechin Gallate.

Epigallocatechin gallate (EGCG) is a compound with very high therapeutic potential in the treatment of osteoporosis and cancer. The disadvantages of this compound are its low stability and low bioavailability. Therefore, carriers for EGCG are sought to increase its use. In this work, new carriers are proposed, i.e., zeolites containing divalent ions of magnesium, calcium, strontium, and zinc in their structure. EGCG is retained on the carrier surface by strong interactions with divalent ions. Due to the presence of strong interactions, EGCG is released in a controlled manner from the carrier-ion-EGCG drug delivery system. The results obtained in this work confirm the effectiveness of the preparation of new carriers. EGCG is released from the carriers depending on the pH; hence, it can be used both in osteoporosis and in the treatment of cancer. The divalent ion used affects the sorption and release of the drug. The obtained results indicate the great potential of the proposed carriers and their advantage over the carriers described in the literature.

Release of drugs used in the treatment of osteoporosis from zeolites with divalent ions-Influence of the type of ion and drug on the release profile.

Bisphosphonates are drugs that are used to treat osteoporosis that causes the low mineral density of the bones. These drugs can be delivered in several ways, but each method has disadvantages. Materials with high potential as carriers of these drugs are zeolites with divalent ions. The aim of this study was to investigate the effect of divalent cations (calcium, magnesium, zinc) and drug type (risedronate, zoledronate) on sorption and release of the drug for osteoporosis. It was proved that drug sorption occurs on all zeolites presented in this work. Risedronate sorption was highest in zinc zeolite and lowest in calcium zeolite. In the case of zoledronate, sorption was most effective in magnesium zeolite and the least effective in zinc zeolite. Very large differences in drug release profiles were also observed. Risedronate was released several times longer than zoledronate. The diversity of the results indicates that the examined materials can be used in different types of drug delivery systems. They can be used, for example, intravenously or in the form of implants due to the different release profiles. Furthermore, the proposed carriers also release magnesium and calcium ions which are used in the prevention of osteoporosis, and zinc ions which have antibacterial properties.

Chitosan modified with lanthanum ions as implantable hydrogel for local delivery of bisphosphonates.

Osteoporosis is a disease that affects many people around the world. One group of drugs used to treat it are bisphosphonates. However, they have poor bioavailability and many side effects. Therefore, research around the world is focused on developing bisphosphonate delivery systems. In this paper, we would like to present the design of a hydrogel material with chitosan matrix modified with lanthanum, that could serve as an implantable hydrogel capable of sustained and slow release of Zoledronate. Various research techniques were used to characterize the materials, and the swelling ratio and water solubility were also tested. The conducted research proved that the prepared hydrogel is capable of the long-term release of the Zoledronate. Thanks to this, the prepared material can be successfully used as an implantable hydrogel or a coating on titanium implants for the local delivery of drugs.

Double Hydroxyl Salt as Smart Biocompatible pH-Responsive Carrier for 6-Mercaptopurine.

Hydroxy double salts are layered materials that are considered to be biocompatible. For this reason, research has been initiated on the possibility of their use in drug delivery. Despite their use for several types of drugs, their potential for controlled release of mercaptopurine (MERC) has not been studied. In this work, the synthesized hydroxy double salt (HDS) material was used as a carrier for this drug for the first time. The effectiveness of HDS synthesis has been proven by such techniques as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Based on the FT-IR and energy-dispersive X-ray spectroscopy (EDS) results, the effectiveness of drug sorption was proven. The exact amount of drug retained was determined by the UV-Vis technique. The obtained results indicate that the drug is evenly distributed on the surface of the carrier, which is important during the controlled delivery of drugs. In the most important stage of the research, the effectiveness of drug release in response to changes in the pH of the environment was proven. The drug is not released into an environment that mimics healthy human tissues. It is released only after contact with the acidic environment that usually surrounds cancer cells. The low cellular toxicity of HDS and significant cytotoxic effect of HDS-MERC were confirmed by in vitro studies on MCF-7 human breast and DU145 prostate cancer cell lines and non-cancerous keratinocytes HaCaT. Interestingly, coupling with the HDS carrier increased the cytotoxic effect of MERC towards DU145 cells. Such an "intelligent" drug carrier for mercaptopurine has not been previously described in the literature. The obtained results indicate its great potential.

Chitosan hydrogel modified with lanthanum as a drug delivery system for epigallocatechin gallate: Investigation of hydrogel - drug interaction by FT-IR and Raman spectroscopy.

In the presented work, chitosan hydrogel modified with lanthanum was obtained for the first time. The hydrogel was used as a carrier in the controlled release of epigallocatechin gallate. The work proved the effectiveness of drug sorption by hydrogel and controlled release in simulated body fluids. The drug was released slowly and in a controlled manner from the carrier. The research techniques used in this work (FT-IR spectroscopy and imaging, Raman spectroscopy, SEM/EDS) allowed to confirm the successful retention of EGCG on the hydrogel surface. On the basis of the EDS mapping, it was possible to confirm the even distribution of the lanthanum ions. Using FT-IR imaging, we verified that the drug was evenly distributed on the entire surface of the prepared material. The antifungal effectiveness of the material has been proven on several types of fungi. The research proved that the prepared material is capable of long-term release of the active substance and has antifungal properties. As a result, the prepared material can be successfully used as an implantable hydrogel or a coating in, e.g. titanium implants.

Zeolitic Imidazolate Framework­8 (ZIF-8) modified titanium alloy for controlled release of drugs for osteoporosis.

The aim of this work was to prepare a biocompatible implant material that enables the release of drug for osteoporosis-risedronate. To achieve this goal, a titanium implant coated with a biocompatible Zeolitic Imidazolate Framework 8 (ZIF-8) layer was prepared that promotes osseointegration at the bone-implant interface. The modifications of the titanium alloy as well as sorption and desorption processes were confirmed using a variety of methods: SEM, EDS XPS, and FT-IR imaging (to determine surface modification, drug distribution, and risedronate sorption), and UV-Vis spectroscopy (to determine drug sorption and release profile). Both the ZIF-8 layer and the drug are evenly distributed on the surface of the titanium alloy. The obtained ZIF-8 layer did not contain impurities and zinc ions were strongly bounded by ZIF-8 layer. The ZIF-8 layer was stable during drug sorption. The drug was released in small doses for 16 h, which may help patients recover immediately after surgery. This is the first case of using ZIF-8 on the surface of the titanium alloy as carrier that releases the drug under the influence of body fluids directly at the site of the disease. It is an ideal material for implants designed for people suffering from osteoporosis.

Drug distribution evaluation using FT-IR imaging on the surface of a titanium alloy coated with zinc titanate with potential application in the release of drugs for osteoporosis.

The drugs most commonly used in the treatment of osteoporosis are bisphosphonates. This disease results in low mineral density and a weakened bone microstructure. The delivery methods for these drugs have many disadvantages, and new ones are being searched for. In this work, biocompatible zinc titanate coated titanium implants were obtained as potential new carriers for drugs. Such a material will release the drug, and it will have antibacterial properties. Gradual release of the bisphosphonate will have a positive effect on the recovery process and osteointegration. In addition, the drug will be released around the affected bones. The effectiveness of the modification and attachment of the drug was confirmed by SEM, XPS, EDS, FT-IR imaging, and UV-VIS. It was shown that the risedronate could be almost completely released upon contact with body fluids within a week. The drug is evenly distributed over the entire surface of the alloy as confirmed by FT-IR imaging. The results presented in this work will allow for the preparation of endoprostheses that release the drug and have antibacterial properties.

Chitosan - zeolite scaffold as a potential biomaterial in the controlled release of drugs for osteoporosis.

Chitosan scaffolds are a potential material in many biomedical applications. A particularly interesting application is their use in bone tissue engineering. Because of their biocompatibility and nontoxicity, they are an ideal material for this application. What is missing from chitosan scaffolds is controlled drug release. They can obtain this property by adding drug carriers. In this work, chitosan­calcium zeolite scaffolds were prepared and used in the controlled release of the drug for osteoporosis - risedronate. Their properties have been compared with those of the popular chitosan-hydroxyapatite scaffold. The zeolite was evenly distributed throughout the scaffold. More drug was retained on the scaffold with the addition of zeolite compared to that with the hydroxyapatite. The new scaffolds have proven to be able to retain the drug and slowly release it in small doses. The results obtained are promising and show great potential for this material in bone tissue engineering.

Evaluation of Laboratory Methods of Determination of SBS Content in Polymer-Modified Bitumens.

The article deals with the issue of determination of the content of SBS (Styrene-Butadiene-Styrene) in polymer-modified bitumens (PMBs). The effect of SBS copolymer on the physical and rheological properties of bitumens has been thoroughly investigated and widely described in the literature. Condition surveys of structures and evaluation of the properties of materials used at construction sites have become a huge challenge for construction engineering. Determination of the content of SBS modifier in various building materials (asphalt mixtures and bituminous waterproofing compounds) is a good example in this respect. Based on the laboratory tests, mid-infrared spectroscopy was found to be the most effective analytical method. It can be used for easy detection of the presence of SBS in a modified bitumen. However, quantitative analysis is an issue that calls for research. Currently, there are no standard guidelines, whether national or European, that would regulate the method of testing. Three test methods were assessed in this study: the AASHTO T302-15 standard method and two Australian methods described in codes of practice (T521 and Q350) developed by the local authorities, which define a standard way of determining the amount of SBS in polymer-modified bitumens. The tests were carried out on standard controls and samples sourced from the industry. The above-mentioned test methods were assessed in terms of accuracy of determination, reliability of results obtained on the industrial samples, level of complexity of the test procedure, sample preparation techniques and the type of the required reagents.

Monitoring x-ray beam damage on lipid films by an integrated Brewster angle microscope/x-ray diffractometer.

We describe an integrated Brewster angle microscope (BAM), Langmuir trough, and grazing incidence x-ray diffraction assembly. The integration of these three techniques allows for the direct observation of radiative beam damage to a lipid monolayer at the air-water interface. Although beam damage has been seen in x-ray measurements, it has not been directly observed in situ at the micron scale. Using this integrated assembly, we examined the effects of radiative beam damage on Langmuir monolayers of 1,2-dimyristoyl-sn-glycero-3-[phospho-L-serine] (DMPS), 1:1 DMPS:1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, and 1:1 DMPS:1,2-dioleoyl-sn-glycero-3-phosphocholine held at a constant surface pressure. For constant surface pressure experiments, we observed a marked decrease in the surface area of the film upon exposure to the beam due to photodissociation. For a condensed lipid film, a change in refractive index of the film was observed post-beam-exposure, indicating areas of damage. For DMPS in an oxygenated environment, the Bragg peak intensity decreased with beam exposure. In mixed monolayer systems, with saturated and unsaturated lipids, an increase in the number of small saturated lipid domains was seen as the unsaturated lipid was preferentially damaged and lost from the monolayer. We show that BAM is a highly effective technique for in situ observation of the effects of radiative damage at the air/water interface during a synchrotron experiment.

Ordered nanoclusters in lipid-cholesterol membranes.

X-ray diffraction of sphingomyelin-dihydrocholesterol (SM-DChol) monolayers revealed short-ranged ( approximately 25 A) 2D ordering. These nanoclusters show two distinct regions: below the cusp point of the phase diagram (35 mol% DChol), a constant d spacing was observed; above the cusp, the d spacing increases linearly with DChol in accordance to Vegard's law for binary alloys. The components in this lipidic alloy are thus a 65ratio35 SM-DChol entity and excess DChol. Reflectivity data further support the emergence above the cusp of an uncomplexed DChol population with greater vertical mobility.

Cholesterol displacement from membrane phospholipids by hexadecanol.

Adding cholesterol to monolayers of certain phospholipids drives the separation of liquid-ordered from liquid-disordered domains. The ordered phases appear to contain stoichiometric complexes of cholesterol and phospholipid. Furthermore, it has been suggested that the cholesterol in these complexes has a low chemical activity compared to that of the free sterol; i.e., that in excess of the phospholipid binding capacity. We have now tested the hypothesis that the membrane intercalator 1-hexadecanol (HD) similarly associates with phospholipids and thereby displaces the complexed cholesterol. HD introduced into monolayers of pure dimyristoylphosphatidylcholine generated highly condensed (stable and solid) domains. In contrast, the phase behavior of mixed monolayers of the phospholipid, sterol, and alcohol suggested that HD could substitute for cholesterol mole for mole in promoting liquid-ordered domains. We also found that the transfer of cholesterol from mixed monolayers to aqueous cyclodextrin was greatly stimulated by the presence of HD, but only at levels sufficient to competitively displace the sterol from the phospholipid. This enhanced efflux was interpreted to reflect an increase in uncomplexed cholesterol. We conclude that HD forms complexes with dimyristoylphosphatidylcholine that are surprisingly similar to those of cholesterol. HD competitively displaces cholesterol from the phospholipid and thereby increases its chemical activity.

Evidence for lipid/cholesterol ordering in model lipid membranes.

It has been postulated that for a binary mixture of phospholipid and cholesterol, phospholipid/cholesterol complexes are formed. Using grazing incidence x-ray diffraction, we have obtained evidence for lipid/cholesterol ordering in model membranes. Scattering features consistent with the existence of lipid/cholesterol complexes persist to high surface pressures even though fluorescence microscopy suggests a homogeneously fluid phase. Contrary to pure phospholipid and cholesterol systems, the resulting lattice spacing, integrated scattering intensity, and coherence lengths of these complexes are almost independent of surface pressure. Furthermore, the single peak observed in these mixed systems is very broad, suggesting that the extent of order for a single scattering structure only persists over a few molecules. This observation is consistent with these complexes being dynamic structures.