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.

Zinc-doped hydroxyapatite as a pH responsive drug delivery system for anticancer drug 6-mercaptopurine.

6-Mercaptopurine (6MP) is commonly used in the treatment of acute lymphoblastic leukemia as an important agent in maintenance therapy. Despite its therapeutic benefits, 6MP has some limitations during therapy. Taking into account the disadvantages during 6MP therapy, there is a great need to create an appropriate delivery system for this drug. 6MP contains in its structure nitrogen and sulfur atoms capable of forming coordination compounds with metal ions, for example zinc. Therefore, in this work, we prepared biocompatible hydroxyapatite (HAp) doped with zinc ions, and used it as a carrier for 6MP. Doped HAp has not been used as a carrier for this drug before. The work proved that the prepared carrier-drug system has a particle size of about 130 nm, which indicates its potential for intravenous delivery. In addition, in an acidic environment (imitating cancer cells), the carrier agglomerates allow targeted release of the drug. The drug is evenly distributed, which indicates that the doses released from it will always be comparable. The release of the drug in a neutral environment is long-lasting in controlled doses, whereas in an acidic environment it is immediate. The obtained results indicate the high potential of the material in both slow-release and cancer-targeted release of 6MP.

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.

Surface Modification of Ti6Al4V ELI Titanium Alloy by Poly(ethylene-alt-maleic anhydride) and Risedronate Sodium.

With the simultaneous increase in the number of endoprostheses being performed, advances in the field of biomaterials are becoming apparent-whereby the materials and technologies used to construct implants clearly improve the implants' quality and, ultimately, the life of the patient after surgery. The aim of this study was to modify the titanium alloy Ti6Al4V ELI used in the construction of hip joint endoprostheses. This is why the continuous development of biomaterials is so important. This paper presents the results of research for a new application of polymer poly(ethylene-alt-maleic anhydride) as a drug release layer, placed on the surface of a titanium alloy. The obtained layers were analyzed using Raman spectroscopy (spectra and maps), Fourier transform infrared spectroscopy (spectra and maps), contact angle measurements as well as scanning electron microscopy and energy dispersive spectroscopy imaging and topography analysis. The results confirmed that the polymer layer obtained on the plate surface after the alkali heat treatment process is much better-it binds much more polymer and thus the applied drug. In addition, a longer and more gradual release of the drug was observed for the alkali heat treatment modification than for H2O2 solution.

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.

Mesoporous Silica Modified with Polydopamine and Zinc Ions as a Potential Carrier in the Controlled Release of Mercaptopurine.

Mercaptopurine is one of the drugs used in the treatment of acute lymphoblastic leukemia. A problem with mercaptopurine therapy is its low bioavailability. This problem can be solved by preparing the carrier that releases the drug in lower doses but over a longer period of time. In this work, polydopamine-modified mesoporous silica with adsorbed zinc ions was used as a drug carrier. SEM images confirm the synthesis of spherical carrier particles. The particle size is close to 200 nm, allowing for its use in intravenous delivery. The zeta potential values for the drug carrier indicate that it is not prone to agglomeration. The effectiveness of drug sorption is indicated by a decrease in the zeta potential and new bands in the FT-IR spectra. The drug was released from the carrier for 15 h, so all of the drug can be released during circulation in the bloodstream. The release of the drug from the carrier was sustained, and no 'burst release' was observed. The material also released small amounts of zinc, which are important in the treatment of the disease because these ions can prevent some of the adverse effects of chemotherapy. The results obtained are promising and have great application potential.

Electrochemical Detection of Borrelia burgdorferi Using a Biomimetic Flow Cell System.

Lyme disease, caused by infection with pathogenic Borrelia bacteria, has emerged as a pervasive illness throughout North America and many other regions of the world in recent years, owing in part to climate-mediated habitat expansion of the tick vectors. Standard diagnostic testing has remained largely unchanged over the past several decades and is indirect, relying on detection of antibodies against the Borrelia pathogen, rather than detection of the pathogen itself. The development of new rapid, point-of-care tests for Lyme disease that directly detects the pathogen could drastically improve patient health by enabling faster and more frequent testing that could better inform patient treatment. Here, we describe a proof-of-concept electrochemical sensing approach to the detection of the Lyme disease-causing bacteria, which utilizes a biomimetic electrode to interact with the Borrelia bacteria that induce impedance alterations. In addition, the catch-bond mechanism between bacterial BBK32 protein and human fibronectin protein, which exhibits improved bond strength with increased tensile force, is tested within an electrochemical injection flow-cell to achieve Borrelia detection under shear stress.

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.

Characterization of Magnesium and Zinc Forms of Sodalite Coatings on Ti6Al4V ELI for Potential Application in the Release of Drugs for Osteoporosis.

Osteoporosis is the most common metabolic disease of the skeletal system and is characterized by impaired bone strength. This translates into an increased risk of low-energy fractures, which means fractures caused by disproportionate force. This disease is quite insidious, its presence is usually detected only at an advanced stage, where treatment with pharmaceuticals does not produce sufficient results. It is obligatory to replace the weakened bone with an implant. For this reason, it is necessary to look at the possibilities of surface modification used in tissue engineering, which, in combination with the drugs for osteoporosis, i.e., bisphosphonates, may constitute a new and effective method for preventing the deterioration of the osteoporotic state. To achieve this purpose, titanium implants coated with magnesium or zinc zeolite were prepared. Both the sorption and release profiles differed depending on the type of ion in the zeolite structure. The successful release of risedronate from the materials at a low level was proven. It can be concluded that the proposed solution will allow the preparation of endoprostheses for patients with bone diseases such as osteoporosis.

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.

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 - 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.

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.

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.

Ionic liquid-assisted synthesis of chitin-ethylene glycol hydrogels as electrolyte membranes for sustainable electrochemical capacitors.

A novel chitin-ethylene glycol hybrid gel was prepared as a hydrogel electrolyte for electrical double-layer capacitors (EDLCs) using 1-butyl-3-methylimidazolium acetate [Bmim][Ac] as a chitin solvent. Examination of the morphology and topography of the chitin-EG membrane showed a homogeneous and smooth surface, while the thickness of the membrane obtained was 27 µm. The electrochemical performance of the chitin-EG hydrogel electrolyte was investigated by cyclic voltammetry and galvanostatic charge/discharge measurements. The specific capacitance value of the EDLC with chitin-EG hydrogel electrolyte was found to be 109 F g-1 in a potential range from 0 to 0.8 V. The tested hydrogel material was electrochemically stable and did not decompose even after 10,000 GCD cycles. Additionally, the EDLC test cell with chitin-EG hydrogel as electrolyte exhibited superior capacitance retention after 10,000 charge/discharge cycles compared with a commercial glass fiber membrane.

Controlled release of the drug for osteoporosis from the surface of titanium implants coated with calcium titanate.

The most popular drugs used to prevent osteoporosis that causes low mineral density and weakened microstructure of bones are bisphosphonates. Bisphosphonates can be administered in several ways, but each delivery method has drawbacks. Due to this, new methods of their delivery are being sought. Titanium implants coated with calcium titanate were prepared in this work as carriers for bisphosphonates. Such a modification has been proposed in order to improve the therapeutic properties of the implant. Slow release of the drug at a constant level will positively affect the recovery process and osteointegration. Furthermore, the drug will be slowly released very close to the area affected by osteoporosis. These studies were confirmed, using a variety of methods: EDS and XPS (to examine surface modification and drug sorption), Raman mapping (to proof the presence of the drug on the entire surface of the material) and UV-VIS spectroscopy (to determine bisphosphonate sorption and release profile). It was proved that the active substance (sorbed on the implant) could be completely released upon contact with body fluids within a month. The obtained results will allow for the production of endoprostheses dedicated to patients with osteoporosis in the future.

Formation of the octadecylphosphonic acid layer on the surface of Ti6Al4V ELI titanium alloy and analysis using Raman spectroscopy.

Increasing life expectancy, a sedentary lifestyle and bone diseases all contribute to an increasing demand for endoprostheses. Currently, the service life of a knee prosthesis is 10-17 years on average, depending on the patient's weight and activity. In addition, the most common reasons for revision operations after implantation are prosthesis loosening and infections resulting from the lack of implant-bone connection. That is why it is so important to constantly search for new materials or improve the current methods of obtaining biomaterials and modifying their surfaces. The main goal of the research is to improve the bonding of hydroxyapatite (HA) on the surface of titanium alloy, which is used in the construction of endoprostheses. At this stage of the research, octadecylphosphonic acid (ODPA) deposited on the surface of the Ti6Al4V ELI alloy was analyzed. To verify the layer, HA attachment (the precipitation process) was first checked, and then the modified plates were immersed in a synthetic body fluid (SBF) to simulate the conditions in the living organism. At each stage of the study, the samples were analyzed using: SEM, EDS and Raman spectroscopy - spectral measurements and surface mapping were performed. The study were supplemented by the measurements of the contact angle - checking the wettability of the surface, which is important for the analysis of biomaterials and surface roughness measurements by confocal microscopy. The results shows that ODPA it increases the amount of precipitation of HA when dipped in SBF. Another interesting finding is that the addition of ODPA to the annealed titanium alloy restricts the precipitation of HA on its surface.

Silica-filled methacrylic composites with extremely high compressive strength.

SYLOID® 244 has never been applied as a filler in composites with potential dental application. Therefore, the aim of research was to apply this silica in its unmodified and diazonium salt-modified forms in different mass ratios as fillers in light-cured methacrylic composites. The effectiveness of modification process was confirmed with the use of Raman spectroscopy. Methacrylic composites with the modified and unmodified SYLOID® 244, as well as unfilled resin as a control group were prepared. Their basic physicochemical properties, such as depth of cure, mass stability during incubation in saline, flexural and compressive strengths were examined. A positive effect of SYLOID® 244 modification on the properties of the examined composites was also demonstrated. The obtained results proved the high applicability of SYLOID® 244 as a filler in composites with potential dental applications.

Improving the abrasion resistance of Ti6Al4V alloy by modifying its surface with a diazonium salt and attaching of polyurethane.

Commonly used endoprostheses in the orthopedic industry are those made of Ti6Al4V titanium alloy. Unfortunately, this material has low abrasion resistance, and therefore methods of their modification are still sought. A sensible approach is coating the alloy with a layer of a polymer having higher abrasion resistance. The adhesion of polymers to alloy is low, therefore the alloy requires prior modification. In this work, the alloy was modified with three types of diazonium salt and the influence of substituent on the effectiveness of modification was determined. Then, five or ten polyurethane layers were attached to the surface of the modified alloy. Using Raman mapping, the uniform distribution of layers was proved. Layers are stable in simulated human body fluids. The effectiveness of attaching subsequent layers of polyurethane was also confirmed by nanoindentation. The main focus of this work was to improve the wear resistance of the titanium alloy. The obtained results indicate that the titanium alloy with a polyurethane layer has almost ten times lower coefficient of friction compared to pure alloy. Such a low value has not been described in the literature so far. These results are the first step for obtaining endoprostheses with very high abrasion resistance.

Calcium zeolites as intelligent carriers in controlled release of bisphosphonates.

This work describes the synthesis of calcium zeolites (type A and X) and their use as drug carriers. This is the first example of using calcium zeolites as intelligent carriers that release drugs under the influence of body fluids. Both zeolites and zeolite/drug systems have been extensively characterized. It has been proven that calcium zeolites can be used as carriers of bisphosphonates (drugs against skeletal system diseases). This is due to the fact that phosphonate groups have strong interactions with calcium ions. The sorption of risedronate on zeolites in the sodium form was also carried out, but it was ineffective. The lack of effectiveness of sorption on the sodium zeolites confirms the theoretical assumptions presented in this work. Sorption occurred faster on type A zeolites while the release is faster for type X zeolites. Loading capacity (LC%) were at least 10% for both zeolite forms. The release may take over 100 h depending on the form of zeolite which will be used. The obtained materials have great potential as a drug carrier in enteric-coated tablets as well as an element of implants allowing for controlled drug release.