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.

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.

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.

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.