Tetramethylguanidinium‐polyallylamine (Tmg‐PA): A new class of nonviral vector for efficient gene transfection

Highly toxic polyallylamine (PA) was reacted with a varying amount of a novel linker, 6‐(N,N,N′,N′‐tetramethylguanidinium chloride) hexanoic acid (Tmg‐HA), to prepare a series of tetramethylguanidinium‐PA (Tmg‐PA) polymers, which were used as vectors for gene transfection. The extent of attachment of the linker, Tmg‐HA, to the PA backbone was determined by 2,4,6‐trinitrobenzene sulfonic acid assay. The modified polymers (Tmg‐PAs), when complexed with pDNA, exhibited good condensation ability. The nanoparticles, so formed, were characterized by their size and zeta potential and were subsequently evaluated for their toxicity and transfection ability on various mammalian cells, viz., HeLa, CHO, and HEK 293 cells. Mobility shift assay revealed that on increasing the percent substitution of Tmg‐HA onto PA (from Tmg‐PA1 to Tmg‐PA6), relatively higher amounts of modified polymers were required to retard the mobility of a fixed amount of DNA. Besides, Tmg‐PA polymers provided sufficient protection (ca. 84–88%) to bound DNA against nucleases and one of the formulations, Tmg‐PA2 (ca. 15% substitution) displayed the highest transfection efficiency outcompeting the commercial transfection reagent, Lipofectamine? with minimal cytotoxicity. More impressively, the transfection efficiency increased despite recording a decrease in the buffering capacity of the grafted polymers suggesting that buffering capacity is not the sole parameter in determining the gene delivery efficiency of a vector system. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Site‐Selectively Coated,Densely‐Packed Microprojection Array Patches for Targeted Delivery of Vaccines to Skin

Densely packed dry‐coated microprojections are shown to deliver vaccines to targeted locations within the skin that are rich in immune cells, thus inducing protective immune responses against a lethal virus challenge. Selectively limiting the antigen coating to the tips of the projections, which penetrate the skin, would significantly reduce the amount of vaccine required in immunization. In this paper a simple technique, dip‐coating the microprojections, is introduced to meet this goal. By increasing the coating solution viscosity, an otherwise strong capillary action is mitigated and the desired controlled coating length on projections is achieved. Following application to the skin, most of the coated vaccine material is rapidly released from the projections (82.6% in mass within 2 min) to the target locations within the skin strata and a potent immune response is induced when a conventional influenza vaccine (Fluvax) is tested in a mouse model. The utility of this coating approach to a variety of molecules representative of vaccines (e.g., chicken egg ovalbumin (OVA) protein, DNA, and fluorescent dyes) is demonstrated. These collective attributes, together with the simplicity of the approach, position the dip‐coating method for practical utility in large vaccination campaigns.     

Synthesis of self‐assembled sphingolipid conjugates and their morphology effect on anticancer therapeutic potency

The shape of self‐assembling polymer–drug conjugates, influencing the cellular uptake, is one of the important factors to be considered for effective drug delivery. In this study, we described synthesis of polymeric drug conjugates of different morphologies with phytosphingosine (PHS) as a hydrophobic model drug and poly(amino acid) as a hydrophilic host polymer. By varying the amount of PHS grafted to poly(amino acid), PHS–poly(amino acid) conjugates exhibited morphological transition from spherical to worm‐like micellar aggregates in the aqueous media. We investigated the physicochemical properties of self‐assembled structures in terms of hydrodynamic size, surface charge, and critical aggregation concentration. The anticancer therapeutic potency of these self‐assembled structures was also discussed in terms of cellular uptake and cytotoxicity of prodrug micelles as a function of dose and time by in vitro cell study. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A branch and cut algorithm for the location-routing problem with simultaneous pickup and delivery

This paper addresses a location-routing problem with simultaneous pickup and delivery (LRPSPD) which is a general case of the location-routing problem. The LRPSPD is defined as finding locations of the depots and designing vehicle routes in such a way that pickup and delivery demands of each customer must be performed with same vehicle and the overall cost is minimized. We propose an effective branch-and-cut algorithm for solving the LRPSPD. The proposed algorithm implements several valid inequalities adapted from the literature for the problem and a local search based on simulated annealing algorithm to obtain upper bounds. Computational results, for a large number of instances derived from the literature, show that some instances with up to 88 customers and 8 potential depots can be solved in a reasonable computation time.     

The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers as drug carriers

The characters of self-assembly core/shell nanoparticles of amphiphilic hyperbranched polyethers (HP-g-PEO) as drug carriers were investigated. The HP-g-PEO consisting of hydrophobic HP-g-PEO core and hydrophilic poly(ethylene glycol) arms was prepared by the cation ring-opening polymerization. A series of HP-g-PEO samples with different degree of branching (DB) were synthesized under various reaction temperatures. Nanoparticles (NP) were obtained by self-assembly of HP-g-PEO in aqueous media. The structure of resulting HP-g-PEO was characterized by IR, ¹³CNMR and GPC. Dynamic light scattering and transmission electron microscopy were applied to characterize the sizes and size distributions of NP. The results demonstrated that the mean diameters of NP were less than 100 nm, which exhibited uniform spherical formations and narrow size distributions. Using hydrophobic drug Probucol (PRO) as model drug, the particle sizes of drug loaded NP were larger than relative blank NP. The drug loading efficiency (LE) and incorporation efficiency (IE) of these NP were achieved to 35 and 89%, respectively. The in vitro release of PRO from the NP exhibited a sustained release and the cumulative drugs released for more than 600 h. The most important factor to affect drug release was the value of DB of HP-g-PEO. With the DB of HP-g-PEO increasing, the size and size distribution of NP decreased as well as the release rate. However, the small DB was beneficial to the LE of NP. Nanoparticle size and size distribution, LE, IE, and drug release rate were slightly affected by the initial solution concentration of polyethers. The co-incorporated hydrophilic drug had influence slightly on the release of drug from drug loaded NP. The results of in vitro drug release suggested that the core/shell NP performed good controlled release behaviors with potential practice as novelty drug delivery vehicles.     

Design and Analysis of Optimal Multi-Level Hierarchical Mobile IPv6 Networks

Hierarchical Mobile IPv6 (HMIPv6) is an enhanced version of Mobile IPv6 designed to reduce signaling overhead and to support seamless handoff in IP-based wireless/mobile networks. To support more scalable services, HMIPv6 networks can be organized as the form of a multi-level hierarchy architecture (i.e., tree structure). However, since multi-level HMIPv6 networks incur additional packet processing overhead at multiple mobility agents, it is important to find the optimal hierarchy level to minimize the total cost, which consists of the location update cost and the packet delivery cost. In this paper, we investigate this problem, namely the design of an optimal multi-level HMIPv6 (OM-HMIPv6) network. To accomplish this, we design a function to represent the location update cost and the packet delivery cost in multi-level HMIPv6 networks. Based on these formulated cost functions, we calculate the optimal hierarchy level in multi-level HMIPv6 networks, in order to minimize the total cost. In addition, we investigate the effects of the session-to-mobility ratio (SMR) on the total cost and the optimal hierarchy. The numerical results, which show various relationships among the network size, optimal hierarchy, and SMR, can be utilized to design an optimal HMIPv6 network. In addition, the analytical results are validated by comprehensive simulations. Sangheon Pack received his B.S. (2000, magna cum laude) and Ph.D. (2005) degrees from Seoul National University, both in computer engineering. He is a post doctor fellow in the School of Computer Science and Engineering at the Seoul National University, Korea. He is a member of the IEEE and ACM. During 2002–2005, he was a recipient of the Korea Foundation for Advanced Studies (KFAS) Computer Science and Information Technology Scholarship. He has been also a member of Samsung Frontier Membership (SFM) from 1999. He received a student travel grant award for the IFIP Personal Wireless Conference (PWC) 2003. He was a visiting researcher to Fraunhofer FOKUS, German in 2003. His research interests include mobility management, wireless multimedia transmission, and QoS provision issues in the next-generation wireless/mobile networks. Yanghee Choi received B.S. in electronics engineering from Seoul National University, M.S. in electrical engineering from Korea advanced Institute of Science, and Doctor of Engineering in Computer Science from Ecole Nationale Superieure des Telecommunications (ENST) in Paris, in 1975, 1977 and 1984 respectively. Before joining the School of Computer Engineering, Seoul National University in 1991, he has been with Electronics and Telecommunications Research Institute (ETRI) during 1977–1991, where he served as director of Data Communication Section, and Protocol Engineering Center. He was research student at Centre National d'Etude des Telecommunications (CNET), Issy-les-Moulineaux, during 1981–1984. He was also Visiting Scientist to IBM T.J. Watson Research Center for the year 1988–1989. He is now leading the Multimedia Communications Laboratory in Seoul National University. He is also director of Computer Network Research Center in Institute of Computer Technology (ICT). He was editor-in-chief of Korea Information Science Society journals. He was chairman of the Special Interest Group on Information Networking. He has been associate dean of research affairs at Seoul National University. He was president of Open Systems and Internet Association of Korea. His research interest lies in the field of multimedia systems and high-speed networking. Minji Nam received her B.S. and M.S degrees in Computer Science and Engineering from Seoul National University in 2003 and 2005, respectively. From 2005, she has worked on Portable Internet Development Team for Korea Telecom. Her research interests are mobile networks, portable internet technology (IEEE 802.16) and Mobile IPv6.