Preparation of 5-Fluorouracil loaded zinc-doped hydroxyapatite and evaluation as anticancer

Zinc- (Zn) doped hydroxyapatite (HAp) were prepared by sol-gel method. Zinc-doped hydroxyapatite (ZnHAp) and HAp were analyzed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The Rietveld analysis revealed that the HAp and 7ZnHAp powders obtained by sol-gel method have a monophasic hydroxyapatite structure belonging to the P63/m spatial group. The results obtained from the ultrasound characterization of HAp and ZnHAp are also presented in this study. The effect of zinc concentration on properties that were deduced from ultrasonic measurements are studied in the case of a significant zinc concentration (xZn = 0.07). From the values of the ultrasonic waves velocities were determined by the pairs of elastic coefficients of the suspensions (Young modulus E, Poisson coefficient ν), which have proven to be similar to those determined by other authors.

This study aimed to investigate the biological response induced by hydroxyapatite (HAp) and zinc-doped HAp (ZnHAp) in human gingival fibroblasts and to explore their antimicrobial activity. The ZnHAp (with xZn = 0.00 and 0.07) powders, synthesized by the sol-gel method, retained the crystallographic structure of pure HA without any modification. Elemental mapping confirmed the uniform dispersion of zinc ions in the HAp lattice. The size of crystallites was 18.67 ± 2 nm for ZnHAp and 21.54 ± 1 nm for HAp. The average particle size was 19.38 ± 1 nm for ZnHAp and 22.47 ± 1 nm for HAp. Antimicrobial studies indicated an inhibition of bacterial adherence to the inert substrate. In vitro biocompatibility was tested on various doses of HAp and ZnHAp after 24 and 72 h of exposure and revealed that cell viability decreased after 72 h starting with a dose of 31.25 µg/mL. However, cells retained membrane integrity and no inflammatory response was induced. High doses (such as 125 µg/mL) affected cell adhesion and the architecture of F-actin filaments, while in the presence of lower doses (such as 15.625 µg/mL), no modifications were observed. Cell proliferation was inhibited after treatment with HAp and ZnHAp, except the dose of 15.625 µg/mL ZnHAp at 72 h of exposure, when a slight increase was observed, proving an improvement in ZnHAp activity due to Zn doping.

This study explores the effect of zinc (Zn) content on the physicochemical characteristics, photocatalytic activity, and antibacterial activity of hydrothermally synthesized hydroxyapatite (HAp). Zinc doped HAp (Zn-HAp) was synthesized with varying Zn content of 1, 2 and 5 wt%, and characterized using XRD, FTIR, UV-Vis DRS, TEM, and zeta potential analysis. Characterization results showed that Zn was successfully dopped into the HAp structure without forming its own ZnO phase, with a decrease in crystallite size and band gap. Photocatalytic activity test was conducted by degradation of tetracycline (TC) antibiotic using UV light. The results show that Zn-HAp has higher photocatalytic activity than pure HAp, with the highest degradation efficiency of 90.48% obtained at 1Zn-HAp. The photocatalytic activity increased as the band gap decreased, which was facilitated by Zn doping. In addition, antibacterial tests against Escherichia coli and Staphylococcus aureus showed that Zn-HAp had a larger inhibition zone than pure HAp, indicating an increase in antibacterial activity, especially at higher Zn concentrations. HIGHLIGHTS Zinc-doped hydroxyapatite with a varied zinc have been synthesized by hydrothermal method. Increasing Zn content in Zn-HAp affects to reduce crystallite size and band gap energies The reduced band gap energy leads to the enhanced photocatalytic activity. Zn-HAp samples show the higher tetracycline photocatalytic activity compared to HAp at 90.84 %. Zn-HAp samples showed good antibacterial activity against Eschericia coli and Staphylococcus aureus. GRAPHICAL ABSTRACT

Bacterial resistance and the demand for novel antibacterial strategies represent major challenges in contemporary medicine. In this study, zinc-doped hydroxyapatite (Zn-HA) samples with 3, 5, and 10 wt% Zn(II) were synthesized using wet precipitation synthesis and sintered at 700 and 800 °C. The samples were characterized by X-ray Diffraction, Fourier Transform Infrared Spectroscopy, Raman Spectroscopy, and Scanning Electron Microscopy. The antimicrobial properties of the Zn-HA were tested against four bacterial strains-Staphylococcus aureus, Enterococcus faecalis, Salmonella typhimurium, Escherichia coli-and the fungus Candida albicans. Both 5 wt% and 10 wt% Zn-HA effectively inhibited the growth of all microorganisms. Notably, 10wt% Zn-HA exhibited the best results, with inhibition rates of 50.2% against S. aureus, 36.5% against E. faecalis, 47.5% against P. aeruginosa, 31.8% against E. coli, and 24.7% against C. albicans. There were no significant differences in the growth of adipose mesenchymal stem cells between the prepared samples and the control. For osteogenic differentiation, dye uptake was 1.2 times higher for HA and 5 wt% Zn-HA, and 1.3 times higher for 3 wt% Zn-HA compared to the control. These results suggest that developed ceramics may be effective in regenerative medicine, paving the way for innovative treatments.

The purpose of this study was preparation of a multilayer electrospun poly (lactic‐co‐glycolic acid) (PLGA)‐based guided bone regeneration (GBR) membrane with controlled shrinkage behavior and alveolar bone regeneration property. First, PLGA copolymer, and zinc‐doped hydroxyapatite (Zn‐HAp) particles were prepared and characterized using fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), proton nuclear magnetic resonance, and X‐ray diffraction analysis. Since the electrospun PLGA scaffolds showed about 80% shrinkage at physiological conditions (phosphate‐buffered saline, 37°C), the effect of factors such as fiber‐alignment, and additives including natural polymers such as gelatin and chitosan, and Zn‐HAp particles; as well as solution preparation method was investigated on the shrinkage ratio. The results showed that it is possible to eliminate the shrinkage of the scaffold in the physiological environment through appropriate design of a tri‐layer PLGA‐CHI/PLGA‐Gel/PLGA‐Gel‐ZnHAp membrane. The designed tri‐layer membrane demonstrated a bubble point smaller than 7 μm, and improved mechanical properties compared with the individual sub‐layer scaffolds. Additionally, it exhibited enhanced antibacterial activity when compared with a similar three‐layer membrane in which HAp was used instead of Zn‐HAp. This observation suggests a synergistic antibacterial effect resulting from the presence of both zinc ions in Zn‐HAp and chitosan . Osteogenic differentiation of adipose‐derived mesenchymal stem cells cultured on the optimal multilayer composite scaffold, was investigated using alkaline phosphatase and Alizarin red staining assays, and the results suggested that the scaffold could support osteogenic differentiation of the stem cells. The designed membrane was implanted in critical size (1 cm) mandibular defects in dogs, and bone regeneration was monitored by computed tomography. Defects treated with the GBR membrane, and the control group showed 69.31% and 44.63%, newly mineralized tissue, respectively, after 8 weeks post implantation. Based on our results, the engineered 3‐layer scaffold is a promising candidate as a GBR membrane for periodontal applications.

In bone disorders infections are common. The concentration of majority of antibiotics is very low in the bone tissue. A high local dose can be obtained from the ciprofloxacin-loaded hydroxyapatite nanoparticles. The present study is aimed at developing the use of hydroxyapatite and zinc-doped hydroxyapatite nanoparticles as a carrier for ciprofloxacin drug delivery system. The ciprofloxacin-loaded hydroxyapatite and zinc-doped hydroxyapatite have a good antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Hydroxyapatite and zinc-doped hydroxyapatite were prepared and characterized using X-ray diffraction, Transmission electron microscopy and inductively coupled plasma optical emission spectrometry. They were loaded with ciprofloxacin using optimized drug loading parameters. Drug loading, in vitro drug release and antimicrobial activity were analyzed. The influence of zinc on the controlled release of ciprofloxacin was analyzed. The results show that the presence of zinc increases the drug release percentage and that the drug was released in a controlled manner.

Multiscale connections between morphology and chemistry in crystalline, zinc-substituted hydroxyapatite nanofilms designed for biomedical applications

In vitro degradation behavior, antibacterial activity and cytotoxicity of TiO2-MAO/ZnHA composite coating on Mg alloy for orthopedic implants

This study proves that the new developed zinc-doped hydroxyapatite (ZnHAp) colloids by an adapted sol-gel method can be widely used in the pharmaceutical, medical, and environmental industries. ZnHAp nanoparticles were stabilized in an aqueous solution, and their colloidal dispersions have been characterized by different techniques. Scanning Electron Microscopy (SEM) was used to get information on the morphology and composition of the investigated samples. Energy-dispersive X-ray spectroscopy (EDX) analysis confirmed the elemental compositions of ZnHAp colloidal dispersions. The homogeneous and uniform distribution of constituent elements (zinc, calcium, phosphorus, oxygen) was highlighted by the obtained elemental mapping results. The X-ray diffraction (XRD) results of the obtained samples showed a single phase corresponding to the hexagonal hydroxyapatite. The characteristic bands of the hydroxyapatite structure were also evidenced by Fourier-transform infrared spectroscopy (FTIR) analysis. For a stability assessment of the colloidal system, ζ-potential for the ZnHAp dispersions was estimated. Dynamic light scattering (DLS) was used to determine particles dispersion and hydrodynamic diameter (DHYD). The goal of this study was to provide for the first time information on the stability of ZnHAp particles in solutions evaluated by non–destructive ultrasound-based technique. In this work, the influence of the ZnHAp colloidal solutions stability on the development of bacteria, such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), was also established for the first time. The antimicrobial activity of ZnHAp solutions was strongly influenced by both the stability of the solutions and the amount of Zn.

Current trends in endosseous implant research are focused on the modification of microdesign of implants to achieve early and strong osseointegration. This study compares the influence of zinc doped hydroxyapatite (ZnHAp) coated, hydrothermally treated (HT) and machined Ti6Al4V (control) implants on osseointegration. The surface characterisation and microbial affinity test for implants were performed. Twenty seven (27) cylinders (3 types in each animal) were placed in the mandible of 9 black Bengal goats. Bone-implant interface was examined with histological, radiological parameters and scanning electron microscopy at 6, 12, and 24 weeks post-implantation. Surface roughness alterations of bone-separated implants were analysed by non-contact profilometer with time. The ZnHAp coated implants revealed direct and early bone-implant contact but high bacterial adherence and coating cracks. Low bacterial affinity and early strong bony integration was observed with HT implants. Poor bacterial affinity and delayed but strong fixation was evident with control implants. Based on the results of laboratory and animal experiments, we conclude that the hydrothermal modification of titanium implant is the more suitable way to achieve safe and effective osseointegration than the other two implant types for endosseous application.

The aim of the current research work was to study the physicochemical and biological properties of synthesized zinc doped hydroxyapatite (ZnHAp) nanoparticles with Zn concentrationsxZn=0(HAp),xZn=0.07(7ZnHAp), andxZn=0.1(10ZnHAp) for potential use in biological applications. The morphology, size, compositions, and incorporation of zinc into hydroxyapatite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), Raman scattering, and X-Ray Photoelectron Spectroscopy (XPS). In addition, the cytotoxicity of ZnHAp nanoparticles was tested on bothE. colibacteria and human hepatocarcinoma cell line HepG2. The results showed that ZnHAp nanoparticles (HAp, 7ZnHAp, and 10ZnHAp) have slightly elongated morphologies with average diameters between 25 nm and 18 nm. On the other hand, a uniform and homogeneous distribution of the constituent elements (calcium, phosphorus, zinc, and oxygen) in the ZnHAp powder was noticed. Besides, FTIR and Raman analyses confirmed the proper hydroxyapatite structure of the synthesized ZnHAp nanoparticles with the signature of phosphate, carbonate, and hydroxyl groups. Moreover, it can be concluded that Zn doping at the tested concentrations is not inducing a specific prokaryote or eukaryote toxicity in HAp compounds.

Three‐dimensional bioactive, antioxidant, and porous nanocomposite scaffolds are inevitable to avoid dependency and disability in the life cycle. Herein, we develop a facile fabrication protocol of nano porous zinc doped hydroxyapatite (Zn‐HAp) scaffold enhanced by polysaccharide polymeric structure for bone tissue engineering applications. The bioactive nano scaffold exhibit opens porous assembly that sustains its flexible and robust nature and promotes efficient linking capability. Moreover, nano scaffold geometry and its porosity were controlled efficiently in various concentrations of zinc doped hydroxyapatite (Zn‐HAp) nanoparticles. Indeed, the composite scaffolds are retained in a dry shape with a suitable load‐bearing strength adjacent to the cancellous bone. The presence of zinc doped hydroxyapatite in the polymeric matrix of nano scaffold regulates its antibacterial response against different bacterial strains owing to its oxidative stress nature. The antioxidant and biocompatibility of nano‐scaffolds were investigated by DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) scavenging behavior, the scavenging activity of ABTS (2,2‐azino‐bis‐3‐ethylbenzthiazoline‐ 6‐sulphonic acid) radical, and iron‐chelating potential. The observed results reveal that polysaccharide‐dependent porous geometry possesses adequate biocompatibility, radical scavenging behavior, and excellent antibacterial properties that validate it as a suitable candidate material for bone tissue implantation. The unprecedented radical scavenging and antioxidant bioactive nanocomposite scaffold are all set to reshape the future bone tissue implantation.

Nanoparticles are highly used in biological applications including nanomedicine. In this present study, the interaction of HepG2 hepatocellular carcinoma cells (HCC) with hydroxyapatite (HAp), zinc-doped hydroxyapatite, and titanium dioxide (TiO2) nanoparticles were investigated. Hydroxyapatite, zinc-doped hydroxyapatite and titanium dioxide nanoparticles were prepared by wet precipitation method. They were subjected to isochronal annealing at different temperatures. Particle morphology and size distribution were characterized by X-ray diffraction and transmission electron microscope. The nanoparticles were co-cultured with HepG2 cells. MTT assay was employed to evaluate the proliferation of tumor cells. The DNA damaging effect of HAp, Zn-doped HAp, and TiO2 nanoparticles in human hepatoma cells (HepG2) were evaluated using DNA fragmentation studies. The results showed that in HepG2 cells, the anti-tumor activity strongly depend on the size of nanoparticles in HCC cells. Cell cycle arrest analysis for HAp, zinc-doped HAp, and TiO2 nanoparticles revealed the influence of HAp, zinc-doped HAp, and titanium dioxide nanoparticles on the apoptosis of HepG2 cells. The results imply that the novel nano nature effect plays an important role in the biomedicinal application of nanoparticles.

Zinc-doped hydroxyapatite is selective towards graphene oxide and prefers an oxygen concentration of 6.25%.

Zinc plays a crucial role in human bone metabolism. In the present study, zinc-doped hydroxyapatite (Zn-HA) porous microspheres were environment-friendly synthesized through a hydrothermal homogeneous precipitation route by using glutamic acid as the growth regulator. FE-SEM results show that Zn-HA microspheres consist of nanosheets and exhibit relatively uniform spherical morphology with porous and petal-like structure. EDS mapping indicates a homogeneous Zn distribution on the microsphere. The one-step process employed to realize zinc doping in the HA porous microspheres offers a functional route to obtain a green Zn-HA product of considerable potential in multiple fields, such as drug-controlled release matrix, injectable bone defect fillers, delivery carriers for proteins and genes.