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Therapeutic vitamin delivery: Chemical and physical methods with future directions
Rejinold, N. Sanoj,Kim, Hye Kyoung,Isakovic, Abdel F.,Gater, Deborah L.,Kim, Yeu-Chun Elsevier 2019 Journal of controlled release Vol.298 No.-
<P><B>Abstract</B></P> <P>Vitamins are a diverse group of “life nourishing” molecules that are essential for proper childhood development, and for maintaining health throughout adulthood into old age. Vitamin supplementation is an important strategy for reducing the severe and chronic effects of malnutrition in subsets of the population of the developing world. Additionally, the precise role of many vitamins in certain conditions, including cancer and cardiovascular disease, remains an area of active research, although guidelines for vitamin supplementation in otherwise adequately nourished populations remain controversial. This review describes vitamin delivery methods and techniques, focusing on the most recent advances and novel approaches. Specific attention has been given to physical methods and novel formulations for delivery with an emphasis on reporting pros and cons of each technique and highlighting future directions. Of particular interest is the potential for transdermal delivery of certain vitamins, which is an approach that may provide advantages in some populations (e.g. for vitamin D), but that still requires considerable additional research and clinical validation.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Rejinold, N. Sanoj,Yoo, Jisang,Jon, Sangyong,Kim, Yeu-Chun American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.34
<P>Curcumin (CRC) has been widely used as a therapeutic agent for various drug delivery applications. In this work, we focused on the applicability of CRC as a nanodrug delivery agent for doxorubicin hydrochloride (DOX) (commercially known as Adriamycin) coated with poly(ethylene glycol) (PEG) as an effective therapeutic strategy against multidrug-resistant cancer cells. The developed PEG-coated CRC/DOX nanoparticles (NPs) (PEG-CRC/DOX NPs) were well localized within the resistant cancer cells inducing apoptosis confirmed by flow cytometry and DNA fragmentation assays. The PEG-CRC/DOX NPs suppressed the major efflux proteins in DOX-resistant cancer cells. The in vivo biodistribution studies on HCT-8/DOX-resistant tumor xenograft showed improved bioavailability of the PEG-CRC/DOX NPs, and thereby suppressed tumor growth significantly compared to the other samples. This study clearly shows that curcumin nanoparticles could deliver DOX efficiently into the multidrug-resistant cancer cells to have potential therapeutic benefits.</P> [FIG OMISSION]</BR>
Yoo, Jisang,Sanoj Rejinold, N.,Lee, DaeYong,Jon, Sangyong,Kim, Yeu-Chun Elsevier 2017 Journal of controlled release Vol.264 No.-
<P><B>Abstract</B></P> <P>Reactive oxygen species (ROS)- or protease-responsive materials have been utilized as carriers in cancer therapies because ROS and specific proteases are overproduced in cancer cells. Methionine-based polypeptides containing a thioether group are promising candidates due to their ROS-responsiveness which provides a phase transition. Herein, we developed protease-activatable cell-penetrating peptide containing a ROS-responsive methionine, a cell permeable lysine chain, and a matrix metalloproteinase (MMP)-cleavable linker. We designed a poly(<SMALL>L</SMALL>-methionine-<I>block</I>-<SMALL>L</SMALL>-lysine)-PLGLAG-PEG (MLMP) and doxorubicin (DOX) was loaded into the micelle core. The MLMP exhibited MMP-sensitive cleavage and ROS-induced DOX release. Moreover, we confirmed efficient DOX delivery into cancer cells and induction of the apoptotic capability <I>in vitro</I>. In a bio-distribution study, IR-780 dye encapsulated MLMP showed superior tumor targetability with long retention. Furthermore, MLMP (DOX) exhibited outstanding tumor inhibition capability with non-toxicity compared to free DOX, indicating that dual stimuli-MLMP has great potential as an anticancer drug delivery platform.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Jung, Daeyoon,Rejinold, N. Sanoj,Kwak, Jeong-Eun,Park, Su-Hyung,Kim, Yeu-Chun Elsevier 2017 Colloids and surfaces Biointerfaces Vol.159 No.-
<P><B>Abstract</B></P> <P>DNA vaccination with microneedles (MNs) into the skin represents a potential therapeutic approach for the clinical treatment of viral diseases as well as for intradermal genetic immunization. In this study, we investigated a DNA vaccination against the severe fever with thrombocytopenia syndrome virus (SFTSV) delivered by nano-patterned microneedles (nMNs) to improve the efficiency compared to a conventional MN vaccination. Because DNA vaccinations delivered by coated MNs have major disadvantages such as a poor coating efficiency and immunogenicity, additional excipients are necessary. Therefore, we developed nMNs to improve the affinity of stainless steel for plasmid DNA vaccinations. The results show that the nMNs have an improved DNA vaccine loading capacity because their surfaces have an increased hydrophilicity from the high surface/volume ratio. The cytocompatibility analysis also showed a higher cell proliferation when using the nMNs. Finally, the <I>in vivo</I> experiments with balb/c mice vaccinated with the SFTSV DNA vaccine-coated nMNs generated a higher level of cellular immune responses than that of the unmodified MNs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Nano patterned microneedles (nMNs) were developed for improved DNA vaccination. </LI> <LI> nMNs improved DNA vaccine loading capacity owing to their increased hydrophilicity. </LI> <LI> The cytocompatibility analysis also showed higher cell proliferation with the nMNs. </LI> <LI> <I>In vivo</I> study revealed better cellular immune responses for nMNs. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Seok, Hae-Yong,Sanoj Rejinold, N.,Lekshmi, Kamali Manickavasagam,Cherukula, Kondareddy,Park, In-Kyu,Kim, Yeu-Chun Elsevier 2018 Journal of controlled release Vol.280 No.-
<P><B>Abstract</B></P> <P>In this study, we developed novel hyaluronic acid cross-linked zein nanogels (HA-Zein NGs) to deliver the potential anticancer agent curcumin (CRC), a naturally occurring phytochemical drug in cancer cells. <I>In vitro</I> studies showed that they are highly compatible with the tested cell lines. They showed CD44 specific uptake in CT26 cell line more than by the CD44 receptor pre-inhibited CT26 cells. The CRC encapsulated HA-Zein NGs (HA-Zein-CRC NGs) found to exert a specific toxicity against CT26 sparing healthy normal fibroblast cells <I>in vitro</I>. The apoptotic effects were further confirmed with flow cytometry showing that the HA-Zein-CRC NGs exhibited high anticancer activity against the CT26 cells. The <I>in vivo</I> bio-distribution with a CT26 tumor model showed their high tumor accumulation thereby improved antitumor efficacy with a low dosage of CRC, compared to the previous reports. Thus, the preclinical studies clearly showed that these novel HA-Zein NGs would be highly beneficial in encapsulating hydrophobic drugs with improved pharmacokinetics thereby enhancing the therapeutic outcomes.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Yoo, Jisang,Lee, DaeYong,Gujrati, Vipul,Rejinold, N. Sanoj,Lekshmi, Kamali Manickavasagam,Uthaman, Saji,Jeong, Chanuk,Park, In-Kyu,Jon, Sangyong,Kim, Yeu-Chun Elsevier 2017 Journal of controlled release Vol.246 No.-
<P><B>Abstract</B></P> <P>Cell-penetrating peptides (CPPs) have been widely used to deliver nucleic acid molecules. Generally, CPPs consisting of short amino acid sequences have a linear structure, resulting in a weak complexation and low transfection efficacy. To overcome these drawbacks, a novel type of CPP is required to enhance the delivery efficacy while maintaining its safe use at the same time.</P> <P>Herein, we report that a bioreducible branched poly-CPP structure capable of responding to reducing conditions attained both outstanding delivery effectiveness and selective gene release in carcinoma cells. Branched structures provide unusually strong electrostatic attraction between DNA and siRNA molecules, thereby improving the transfection capability through a tightly condensed form. We designed a modified type of nona-arginine (mR9) and synthesized a branched-mR9 (B-mR9) using disulfide bonds. A novel B-mR9/pDNA polyplex exhibited redox-cleavability and high transfection efficacy compared to conventional CPPs, with higher cell viability as well. B-mR9/VEGF siRNA polyplex exhibited significant serum stability and high gene-silencing effects <I>in vitro</I>. Furthermore, the B-mR9 polyplex showed outstanding tumor accumulation and inhibition ability <I>in vivo</I>. The results suggest that the bioreducible branched poly CPP has great potential as a gene delivery platform.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Jeon, Wooyoung,Kim, Yeu-Chun,Hong, Minhee,Rejinold, Sanoj,Park, Kyoungmoon,Yoon, Injoong,Yoo, Sungsik,Lee, Hongweon,Ahn, Jungoh Hindawi 2018 BioMed research international Vol.2018 No.-
<P>The study describes the development of a vaccine using microcrystalline cellulose (Avicel PH-101) as a delivery carrier of recombinant protein-based antigen against erysipelas. Recombinant SpaA, surface protective protein, from a gram-positive pathogen<I> Erysipelothrix rhusiopathiae</I> was fused to a cellulose-binding domain (CBD) from<I> Trichoderma harzianum</I> endoglucanase II through a S3N10 peptide. The fusion protein (CBD-SpaA) was expressed in<I> Escherichia coli</I> and was subsequently bound to Avicel PH-101. The antigenicity of CBD-SpaA bound to the Avicel was evaluated by enzyme-linked immunosorbent (ELISA) and confocal laser scanning microscope (CLSM) assays. For the examination of its immunogenicity, groups of mice were immunized with different constructs (soluble CBD-SpaA, Avicel coated with CBD-SpaA, whole bacterin of<I> E. rhusiopathiae</I> (positive control), and PBS (negative control)). In two weeks after immunization, mice were challenged with 1x10<SUP>7</SUP> CFU of<I> E. rhusiopathiae</I> and Avicel coated with CBD-SpaA induced protective immunity in mice. In conclusion, this study demonstrates the feasibility of microcrystalline cellulose as the delivery system of recombinant protein subunit vaccine against<I> E. rhusiopathiae </I>infection in mice.</P>