Biomimetic Apatite/Natural Polymer Composite Granules as Multifunctional Dental Tissue Regenerative Material.

This study presents a comprehensive evaluation of novel composite biomaterials designed for dental applications, aiming to potentially address the prevalent challenge of dental and periodontal tissue loss. The composites consisted of biomimetic hydroxyapatite (mHA) enriched with Mg2+, CO32-, and Zn2+ ions, type I collagen, alginate, and, additionally, chitosan and sericin. The granules were loaded with ibuprofen sodium salt. The investigation encompassed a morphology characterization, a porosity analysis, a chemical structure assessment, and an examination of the swelling behavior, drug release kinetics (ibuprofen), and release profiles of zinc and magnesium ions. The granules exhibited irregular surfaces with an enhanced homogeneity in the chitosan-coated granules and well-developed mesoporous structures. The FT-IR spectra confirmed the presence of ibuprofen sodium, despite overlapping bands for the polymers. The granules demonstrated a high water-absorption capacity, with delayed swelling observed in the chitosan-coated granules. Ibuprofen displayed burst-release profiles, especially in the G1 and G3 samples. In the case of the chitosan-coated granules (G2 and G4), lower amounts of ibuprofen were released. In turn, there was a significant difference in the released amount of magnesium and zinc ions from the granules, which was most likely caused by their different location in the hydroxyapatite crystals. The cytotoxicity assays confirmed the non-cytotoxic behavior of the biomaterial. These findings suggest the potential applicability of these biomaterials in dental scenarios, emphasizing their multifunctional and biocompatible nature.

Cytotoxicity and antigenotoxicity evaluation of acetylshikonin and shikonin.

Shikonin (SH) is used as a red pigment for food coloring and cosmetics, and has cytotoxic activity towards cancer cells. However, due to strong toxicity SH has limited potential as an anticancer drug. Acetylshikonin (ASH) is one of the SH derivatives with promising anticancer potential. In present study, we attempted to evaluate and compare the cytotoxicity of SH and ASH towards a normal cell line (V79) and in addition to evaluate their antigenotoxic activity. The evaluation was made with the use of the set of cytotoxicity assays with V79 line and the micronucleus test in vitro performed using clinafloxacin (CLFX), ethyl methanesulfonate (EMS) as direct genotoxins and cyclophosphamide (CPA) as indirect genotoxin. For CPA and EMS the simultaneous protocol was used and for CLFX three different variants were performed: pretreatment, simultaneous, and post-treatment. A higher cytotoxic effect was observed for SH. The EC50 values obtained for SH were approximately twofold lower compared to that of ASH. Moreover, ASH exhibited an antigenotoxic potential against CPA-induced genotoxicity, whereas SH has no activity. However, ASH increased the EMS-induced genotoxicity, when SH exhibited no effect. Both compounds decreased the genotoxicity of CLFX in pretreatment and simultaneous protocol. Based on the results of the present study it can be concluded that ASH is less cytotoxic than SH to normal cells and has comparable antigenotoxic potential.

Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems.

Polymeric hydrogels play an increasingly important role in medicine, pharmacy and cosmetology. They appear to be one of the most promising groups of biomaterials due to their favorable physicochemical properties and biocompatibility. The objective of the presented study was to synthesize new poly(chitosan-ester-ether-urethane) hydrogels and to study the kinetic release of genistein (GEN) from these biomaterials. In view of the above, six non-toxic hydrogels were synthesized via the Ring-Opening Polymerization (ROP) and polyaddition processes. The poly(ester-ether) components of the hydrogels have been produced in the presence of the enzyme as a biocatalyst. In some cases, the in vitro release rate of GEN from the obtained hydrogels was characterized by near-zero-order kinetics, without "burst release" and with non-Fickian transport. It is important to note that developed hydrogels have been shown to possess the desired safety profile due to lack of cytotoxicity to skin cells (keratinocytes and fibroblasts). Taking into account the non-toxicity of hydrogels and the relatively highly controlled release profile of GEN, these results may provide fresh insight into polymeric hydrogels as an effective dermatological and/or cosmetological tool.

Polyscias filicifolia (Araliaceae) Hairy Roots with Antigenotoxic and Anti-Photogenotoxic Activity.

Hairy root cultures are considered as a valuable source of bioactive phytoconstituents with expanding applicability for their production. In the present study, hairy root cultures of Polyscias filicifolia (Araliaceae), a traditional Southeast Asian medicinal plant, were established. The transformation with Agrobacterium rhizogenes ATCC 15834 allowed to obtain 15 root lines. The K-1 line, demonstrating the highest growth capabilities, was subjected to further investigations. To enhance the biosynthetic potential of hairy roots, methyl jasmonate elicitation approach was applied (MeJA; at different doses and exposure time), with subsequent transfer of elicited roots to control medium. This strategy resulted in chlorogenic acid production up to 1.59 mg/g dry weight. HPLC-PDA-ESI-MS analysis demonstrated variation in extracts composition and allowed to identify different caffeic and ferulic acid derivatives. Next, cytotoxic, antigenotoxic, and anti-photogenotoxic properties of hairy roots extracts were determined. None of the tested extracts were cytotoxic. In addition, they demonstrated significant antigenotoxic activity with the highest protective potential; up to 52% and 49% of inhibition of induction ratio (IR) induced by the 2-aminoanthracene was revealed for extracts derived from hairy roots elicited for 3 days with 50 µM MeJA and roots elicited for 7 days with 100 µM MeJA and then transferred for 30 days to control medium, respectively. These same extracts exhibited the highest anti-photogenotoxic potential, up to 36% of inhibition of chloropromazine-induced genotoxicity.

Antigenotoxic, Anti-photogenotoxic, and Antioxidant Properties of Polyscias filicifolia Shoots Cultivated In Vitro.

Traditional medicinal plants are an important source of active compounds with potential antimutagenic activity. Polyscias filicifolia Bailey (Araliaceae) is a South Asian traditional herb used as an adaptogenic and cardiac drug. Extracts of P. filicifolia contain a wide range of biologically active compounds like phenolic acids and triterpenoid saponins. In the present study. antigenotoxic potential of three naturally occurring phenolic acids and extracts of P. filicifolia growing in vitro with the addition of elicitors was evaluated against direct (4-nitroquinoline-N-oxide (4NQO) and mitomycin C (MMC)) and indirect mutagens (2-aminoanthracene (2AA)). The evaluation was made using a bacterial umu-test. Moreover, the ability to prevent photogenotoxicity induced by chlorpromazine (CPZ) under UVA irradiation was measured. The phytochemical profiling of examined extracts revealed the presence of numerous compounds with the prevelance of chlorogenic, caffeic, and ferulic acid derivatives; however, saponin fractions were also determined. The antioxidant potential of extracts strictly correlated with their composition. The tested extracts exhibited high antigenotoxic activity if the assay was performed with 2AA and metabolic activation. Moreover, the extracts slightly decreased the MMC-induced genotoxicity. However, an increase of the genotoxic effect was observed in the assay performed with 4NQO. In addition, photo-antigenotoxic activity was observed. In our study, phenolic acids exhibited lower activity than the extracts.

Application of Diethylzinc/propyl Gallate Catalytic System for Ring-Opening Copolymerization of rac-Lactide and ε-Caprolactone.

Biodegradable polyesters gain significant attention because of their wide potential biomedical applications. The ring-opening polymerization method is widely used to obtain such polymers, due to high yields and advantageous properties of the obtained material. The preparation of new, effective, and bio-safe catalytic systems for the synthesis of biomedical polymers is one of the main directions of the research in modern medical chemistry. The new diethylzinc/propyl gallate catalytic system was first used in the copolymerization of ε-caprolactone and rac-lactide. In this paper, the activity of the new zinc-based catalytic system in the copolymerization of cyclic esters depending on the reaction conditions was described. The microstructure analysis of the obtained copolyesters and their toxicity studies were performed. Resulted copolyesters were characterized by low toxicity, moderate dispersity (1.19-1.71), varying randomness degree (0.18-0.83), and average molar mass (5300-9800 Da).

Pamidronate-Conjugated Biodegradable Branched Copolyester Carriers: Synthesis and Characterization.

The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with selenite ions (SeO32-) and a biodegradable branched copolymer-bisphosphonate conjugate as a promising bone substitute material for patients with bone tumours or bone metastasis. A series of biodegradable and branched copolymer matrices, adequate for delivery of bisphosphonate in the bone-deficient area were synthesized and physico-chemically and biologically (cyto- and genotoxicity assays) characterized. Branched copolymers were obtained using a hyperbranched bis-MPA polyester-16-hydroxyl initiator and Sn(Oct)2, a (co)catalyst of the ring-opening polymerization (ROP) of l,l-lactide (LLA) and ε-caprolactone (CL). A new amide bond was formed between the hydroxyl end groups of the synthesized copolymer carriers and an amine group of pamidronate (PAM)-the drug inhibiting bone resorption and osteoclast activity in bone. The dependence of the physico-chemical properties of the copolymer matrices on the kinetic release of PAM from the synthesized branched copolymer conjugate-coated hydroxyapatite granules doped with selenite ions was observed. Moreover, the correlation of these results with the hydrolytic degradation data of the synthesized matrices was evidenced. Therefore, the developed composite porous hydroxyapatite doped with SeO32- ions/biodegradable copolymer-PAM conjugate appears most attractive as a bone substitute material for cancer patients.

Essential Elements and Isoflavonoids in the Prevention of Prostate Cancer.

The intake of selected minerals, especially zinc, calcium and selenium, and high consumption of dietary isoflavones are recognised as factors influencing prostate cancer risk. Moreover, changes in levels of some essential elements are characteristic of the disease. Here, we examined the combined effects of main dietary isoflavonoids (genistein, daidzein and its metabolite, equol) and minerals implicated in prostate cancer, namely zinc, selenium, copper, iron and calcium, on LNCaP prostate cancer cells proliferation. Secondly, we evaluated the influence of the combinations on genotoxicity of model mutagens, 4-nitroquinoline oxide (4NQO) and 2-aminoanthracene (2AA), in the umu test. All combinations of isoflavonoids and minerals inhibited prostate cancer cells growth. However, only mixtures with iron ions had significantly stronger effect than the phytochemicals. Interestingly, we observed that only genistein attenuated genotoxicity of 4NQO. The addition of any tested mineral abolished this effect. All tested isoflavonoids had anti-genotoxic activity against 2AA, which was significantly enhanced in the presence of copper sulphate. Our results indicate that the tested minerals in physiological concentrations had minimal influence on the anti-proliferative activity of isoflavonoids. However, they significantly modulated the anti-genotoxic effects of isoflavonoids against both metabolically activated and direct mutagens. Thus, the minerals intake and nutritional status may modulate protective action of isoflavonoids.