The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy.From the Clinical EditorSpecific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies.

Background: A recently FDA approved 3D printed drug is paving a path for new pharmaceutical manufacturing era. The 3D printing is a novel approach of producing 3D pharmaceuticals from digital designs, in a layer-by-layer fashion. However, traditional manufacturing of drug products is being carried out from decades with well-established manufacturing processes and with well approved regulatory guidelines but these processes are too obsolete in concern of process aptitude and manufacturing flexibility. On the other hand, 3D printing provides a competitive flexibility in terms of personalized drug dosage forms with complex geometries that will be made on-demand with desired drug release kinetics, hence providing the formulator a substantial provision of improvising the safety and efficacy of the drugs. Furthermore, this novel 3D technology allows tailoring of composite tissue scaffolds and sample models for characterization that closely mimic in-vivo simulations. Nevertheless, certain limitations are there in terms of regulatory aspects hindering the launch of 3DP products in the market. Methods: Exhaustive search were made on Google Scholar and PubMed databases concerning 3-D printing methods, drug delivery applications, and past to present evolution of personalized medicine. Results: Although a high magnitude of progress have been made on 3-D printing techniques in a short span of time, still inkjet, nozzle-based deposition, stereolithography and selective laser sintering techniques are the most popular ones. Their application is adapted in the fabrication of tablets, implants, polypills and nanoparticles. Conclusion: 3D printing is revolutionizing the pharma expectations towards customized medicines but still there is a need to explore the aspects of cost, flexibility and bioequivalence. The present review provides a comprehensive account of various 3D printing technologies and highlights the opportunities and key challenges of 3D printing relevant to pharmaceuticals.

Neurological diseases like Alzheimer's disease, epilepsy, parkinsonism, depression, Huntington's disease and amyotrophic lateral sclerosis prevailing globally are considered to be deeply influenced by oxidative stress-based changes in the biochemical settings of the organs. The excess oxygen concentration triggers the production of reactive oxygen species, and even the intrinsic antioxidant enzyme system, i.e. SOD, CAT and GSHPx, fails to manage their levels and keep them under desirable limits. This consequently leads to oxidation of protein, lipids and nucleic acids in the brain resulting in apoptosis, proteopathy, proteasomes and mitochondrion dysfunction, glial cell activation as well as neuroinflammation. The present exploration deals with the evidence-based mechanism of oxidative stress towards development of key neurological diseases along with the involved biomechanistics and biomaterials.

The therapeutic potential of tocotrienol, a member of the vitamin E family of compounds with potent in vitro anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a novel tumor-targeted vesicular formulation of tocotrienol would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo.In this work, we demonstrated that novel transferrin-bearing multilamellar vesicles entrapping -T3 resulted in a dramatically improved (by at least 52-fold) therapeutic efficacy in vitro on A431 cell line, compared to the free drug. In addition, the intravenous administration of tocotrienol entrapped in transferrin-bearing vesicles resulted in tumor suppression for 30% of A431 and 60% of B16-F10 tumors, without visible toxicity. Mouse survival was enhanced by more than 13 days compared to controls administered with the drug solution only. This tumor-targeted, tocotrienol-based nanomedicine therefore significantly improved the therapeutic response in cancer treatment. KEYWORDSTocotrienol; transferrin; tumor targeting; delivery system; cancer therapy 2 1. Introduction Tocotrienol, a member of the vitamin E family of compounds, is currently receiving increased attention because of its promising anti-tumor activity [1,2]. It has been reported to exert its anti-cancer effects through various mechanisms, such as activation of p53, modulation of Bax/Bcl-2 ratio, decrease of oxidative stress and induction of apoptosis [1][2][3][4]. It can also inhibit angiogenesis by downregulating the expression of the vascular endothelial growth factor (VEGF) receptor and blocking intracellular VEGF signaling. In addition, it is able to potentiate apoptosis through inhibition of DNA polymerase and telomerase and of NF-B activation pathway [1][2][3][4]. This wide range of anti-cancer effects therefore makes tocotrienol a very promising therapeutic molecule. However, its efficacy against cancer cells in vivo is hindered by its inability to specifically reach cancer cells at a therapeutic concentration, without affecting normal cells. Given its anti-proliferative properties, it is of the utmost importance to find a strategy to deliver this therapeutic drug specifically to its site of action. On the basis that iron is essential for tumor cell growth and can be effectively carried to tumors by using transferrin receptors overexpressed on cancer cells [5,6], we recently demonstrated that the conjugation of transferrin (Tf) to vesicles entrapping tocotrienol-rich fraction (TRF) extracted from palm oil could lead to tumor regression, and even tumor suppression, on both the tested cancer cell lines, following intravenous injection to a murine model [7][8][9]. It resulted in complete tumor eradication for 50% of B16-F10 tumors and 20% of A431 tumors [7]. The treatments were well tolerated by the animals, without weight loss or apparent signs of toxicity. These previous studies, however, used TRF but did not ev...

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