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Dental biomaterials have revolutionized modern therapies. Untreated dental caries remains the major etiological factor for endodontic treatment, and together with a decreasing rate of tooth loss escalates the importance of continuously improving the materials used for endodontic therapies. Endodontic biomaterials are used for vital pulp therapies, irrigation, intracanal medicaments, obturation and regenerative procedures. These materials offer several functions including: antimicrobial activity, mechanical reinforcement, aesthetics, and therapeutic effects. Vital pulp therapies have seen an improvement in clinical results with an incremental approach to build on the strengths of past materials such as calcium hydroxide and calcium silicates. While sodium hypochlorite remains the gold standard for canal irrigation, numerous nanoparticle formulations have been developed to promote sustained antimicrobial action. Gutta‐percha based bulk fillers remain the most common materials for root filling. However, while multiple studies focus on the development of novel formulations containing drugs, glass derivatives or ionic‐, polymeric‐, or drug‐ loaded nanoparticles, a lack of reliable and long‐term clinical evidence obligates further study as experienced clinicians prefer to use what has worked for decades. This review delves in to the biochemistry of the materials to scrutinize their shortcomings, and where opportunity lies to further enhance their efficacy in endodontic practice. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:201–212, 2020.

A novel theranostic molecule, derived from curcumin (Cur) and naphthoquinone (NQ), allowing for cancer targeting, detection and treatment was previously described and termed CurNQ. To allow for enhanced theranostic capabilities, advanced drug delivery techniques are required. To this end, mesoporous silica nanoparticles (MSN) were synthesized and CurNQ was loaded into its pores to form the novel nanosystem MSN_CurNQ. The formation of the nanosystem aimed to augment the drug delivery of CurNQ through the EPR effect and sustained release. Moreover, the loading of CurNQ into its pores, formed a fluorescent nanoparticle that can be tracked, detected and visualized. Herein, the synthesis of a novel nanosystem is described and its theranostic potential are explored in vitro. MSN with an average size of 108 d.nm, a zeta potential of −42 mV and a PDI of 0.150 were synthesized and were impregnated with CurNQ to form the novel nanosystem MSN_CurNQ. MSN_CurNQ was demonstrated to have pH-responsivity whereby after 96 h, at pH 7.4, 31.5% of CurNQ was released from the MSN compared to 57% release at pH 6.8, corresponding to an increase of 25.5% in release with a 0.6 pH drop. The innate fluorescence was then characterized through confocal and fluorescence microscopy. Microscopy images illustrated the distinct, high intensity innate fluorescence with a high background to target ratio, thus confirming detection capabilities and potentially extending MSN_CurNQ’s application to molecular imaging purposes. Moreover, the chemotherapeutic potential of MSN_CurNQ was demonstrated as cell viability was reduced to below 50% in OVCAR-5, CACO-2, CHLA, and MCF-7 cell lines. Furthermore, MSN_CurNQ displayed tumor specific toxicity whereby the cell viability was reduced to a far greater extent in the cancer cell lines compared to a healthy fibroblast cell line (p = 0.000). Indeed, the novel MSN_CurNQ nanosystem has potential for applications in cancer targeting, detection and treatment.

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Sulpiride (SPR) is a selective antagonist of central dopamine receptors but has limited clinical use due to its poor pharmacokinetics. The aim of this study was to investigate how metal ligation to SPR may improve its solubility, intestinal permeability and prolong its half-life. The synthesis and characterisation of ternary metal complexes [Ru(p -cymene)(L)(SPR)]PF6 (L1 = (R)-(+)-2-amino-3-phenyl-1-propanol, L2 = ethanolamine, L3 = (S)-(+)-2-amino-1-propanol, L4 = 3-amino-1-propanol, L5 = (S)-(+)-2-pyrrolidinemethanol) are described in this work. The stability constant of the [Ru(p -cymene)(SPR)] complex was determined using Job’s method. The obtained value revealed higher stability of the metal complex in the physiological pH than in an acidic environment such as the stomach. The ternary metal complexes were characterised by elemental analysis, Fourier transform infrared spectroscopy (FT-IR), 1H and 13C nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), thermal analyses, Ultraviolet-Visible (UV-Vis). Solubility studies showed higher aqueous solubility for complexed SPR than the free drug. Dissolution profiles of SPR from the metal complexes exhibited slower dissolution rate of the drug. Permeation studies through the pig’s intestine revealed enhanced membrane permeation of the complexed drug. In vitro methyl thiazolyl tetrazolium (MTT) assay showed no noticeable toxic effects of the ternary metal complexes on Caco-2 cell line.

The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan–Poly(vinylpyrrolidone)–Poly(N-isopropylacrylamide) (C–P–N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting following intraperitoneal implantation. The optimum nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a preferential form of intraperitoneal ovarian cancer (OC) chemotherapy. The cross-linked interpenetrating C–P–N hydrogel was synthesized for the preparation of an in situ-forming implant (ISFI). Subsequently, the ISFI was fabricated by encapsulating a nanocomposite comprising of anti-MUC16 (antibody) functionalized methotrexate (MTX)-loaded poly(N-isopropylacrylamide)-b-poly(aspartic acid) (PNIPAAm-b-PASP) nanomicelles (AF(MTX)NM’s) within the cross-linked C–P–N hydrogel. This strategy enabled specificity and increased the residence time of the nanomicelles at tumor sites over a period exceeding one month, enhancing uptake of drugs and preventing recurrence and chemo-resistance. Chemotherapeutic efficacy was tested on the optimal ovarian tumor-bearing Athymic nude mouse model and the results demonstrated tumor regression including reduction in mouse weight and tumor size, as well as a significant (p < 0.05) reduction in mucin 16 levels in plasma and ascitic fluid, and improved survival of mice after treatment with the experimental anti-MUC16/CA125 antibody-bound nanotherapeutic implant drug delivery system (ISFI) (p < 0.05). The study also concluded that ISFI could potentially be considered an important immuno-chemotherapeutic agent that could be employed in human clinical trials of advanced, and/or recurring, metastatic epithelial ovarian cancer (EOC). The development of this ISFI may circumvent the treatment flaws experienced with conventional systemic therapies, effectively manage recurrent disease and ultimately prolong disease-free intervals in ovarian cancer patients.