Overview on natural hydrophilic polysaccharide polymers in drug delivery

Nanotechnology is poised to make potentially revolutionary innovations in areas of biomedical science, such as gene therapy and drug therapy. A recently developed nanodelivery strategy involves the use of hydrophilic polymers as carriers of proteins and siRNA. By controlling the reaction conditions during polymer production, various degrees of anionic charge, cationic charge, and cross‐linking can be added, thereby changing their capabilities as protein and nucleic acid carriers and promoting effective cell membrane permeation. The efficiency of a specific controlled‐release polymeric system is determined in part by its unique physical and chemical properties and biodegradation rate. In this review, we will summarize recent progress in the ability to modify drug release of hydrophilic polymers nanoparticles.     

Dendritic polyglycerol with secondary amine shell as an efficient gene delivery vector with reduced toxicity

Dendritic polycation (PG‐BEN) using polyglycerol as a core and secondary amine shell consisting of N¹,N¹¹‐bisethylnorspermine (BEN) was synthesized. Polymers containing primary amines in the shell (PG‐Nor and PG‐NH₂) were synthesized as controls to allow evaluation of the shell effect on physicochemical and transfection properties of the polymers. All studied polymers condensed DNA and formed polyplexes with sizes less than 110 nm. PG‐BEN and PG‐Nor had a similar transfection activity that was fully comparable with that of the control polyethylenimine. Amongst the studied polymers, PG‐BEN demonstrated the lowest cytotoxicity, suggesting that PG‐BEN is a promising gene delivery vector with favorable transfection/toxicity profile. Copyright © 2014 John Wiley & Sons, Ltd.     

Amine containing cationic methacrylate copolymers as efficient gene delivery vehicles to retinal epithelial cells

Non‐viral gene delivery vectors have emerged as potential alternatives in the field of gene therapy by replacing the biological viral vectors. DNA–cationic polymer complexes are one of the most promising systems to target many inborn or acquired diseases without the utilization of conventional drugs. Despite the excellent binding efficiency of cationic polymers, the gene transfection seems limited to date. In this work, a series of ammonium‐based block‐copolymers with different alkyl side chains (ethyl, butyl, and hexyl) and functionality (alcohol, amine, and alkyl) have been prepared to evaluate their capacity to deliver genetic material. First, different ionic liquid monomers with different pendent functional groups were prepared and characterized. Then, polyplexes elaborated with different polymers at several polymer DNA ratios (w/w) were characterized in terms of size, zeta potential, and DNA binding, release, and protection capacity. Finally, the transfection efficiency and cell viability was evaluated in ARPE19 cells. We found that only the systems containing the amine pendent group were able to transfect ARPE19 cell and, that this amine containing polymer was less cytotoxic even at high polymer/DNA ratios (30:1). In conclusion, our studies suggested that the proper selection of the pendent group substantially impacts overall transfection efficiency of cationic polymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 280–287     

Magnetofection: Magic magnetic nanoparticles for efficient gene delivery

Magnetic nanoparticles (MNPs) have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties. This minireview summarizes the specific gene transfection of magnetic particles (magnetofection) during eversy dynamic process of gene delivery (gene binding, cellular uptake, endosomal escape, intracellular trafficking and in vivo targeting). Meanwhile, the synergistic biomedical application of magnetofection and the effects of MNPs have also been discussed, including magnetic resonance imaging (MRI), magnetic mediated hyperthermia (MMH), Fenton reaction and autophagy. Finally, the clinical prospect of magnetofection was briefly expected.     

Magnetofection: Magic magnetic nanoparticles for efficient gene delivery

Magnetic nanoparticles (MNPs) have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties. This minireview summarizes the specific gene transfection of magnetic particles (magnetofection) during eversy dynamic process of gene delivery (gene binding, cellular uptake, endosomal escape, intracellular trafficking and in vivo targeting). Meanwhile, the synergistic biomedical application of magnetofection and the effects of MNPs have also been discussed, including magnetic resonance imaging (MRI), magnetic mediated hyperthermia (MMH), Fenton reaction and autophagy. Finally, the clinical prospect of magnetofection was briefly expected.     

Preparation of an Organized Film Composed of Polymers,Avidin, and Concanavalin A and Its Binding Properties

The multilayer thin films composed of polymers, avidin, and concanavalin A (Con A) were prepared on the surface of a quartz slide by alternate deposition of anionic and cationic polymers and the proteins. The loading of avidin and Con A in the film was evaluated spectroscopically by using Texas Red tagged avidin and Con A. Avidin molecules assembled in the film caused its binding activity toward biotin and analogue 2-(4′-hydroxyphenylazo)benzoic acid to be retained. The polymer layers contributed to improving stability of the protein film.

Polymer/Con A/avidin composite film on a solid surface.     

Synthesis of Cyclic Polyamines by Enzymatic Generation of an Amino Aldehyde In Situ

Multifunctional polycationic polyamines, for example, used in drug and gene delivery, have product range limitations in their synthesis methods. Here, we synthesize a polyamine by forming a self‐assembling amino aldehyde from the corresponding amino alcohol with horse liver alcohol dehydrogenase (HLADH), followed by reduction. Circular polyamines were synthesized from 3‐amino‐propan‐1‐ol as starting material, analogous to cyclic polyamines formed from azetidin. The product had an isolated yield of 89.7% or 15.3 g L⁻¹. The predicted range of possible polyamine products by this method is broad since many amino alcohols are putative substrates for HLADH. The enzyme also had activity for 2‐amino‐propan‐1‐ol and 2‐amino‐2‐phenyl‐ethanol, for which the enantioselectivity was 330 (S) and 32 (R), respectively.     

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     

Erosion of multilayered films fabricated from degradable polyamines: Characterization and evidence in support of a mechanism that involves polymer hydrolysis

Multilayered polyelectrolyte assemblies fabricated using hydrolytically degradable polyamines ( 1 – 3 ) erode gradually when incubated in physiologically relevant media. This investigation sought to characterize physically and chemically the erosion of films fabricated from these polymers and sodium poly(styrene sulfonate) (SPS) and to investigate specifically the potential role of polymer hydrolysis in governing film erosion. The characterization of erosion using reflective infrared spectroscopy revealed changes in the carbonyl region of the spectrum that were consistent with the generation of polymer hydrolysis products. To evaluate the role of the esters in these materials more directly, we also synthesized a structural analogue of polymer 2 containing amide functionality rather than ester functionality. Assemblies fabricated from this amide-containing polymer did not erode significantly or release SPS into solution when incubated in phosphate-buffered saline (PBS). Finally, we characterized the erosion of assemblies fabricated from polymer 1 in PBS buffer prepared with D₂O rather than H₂O. These assemblies eroded significantly more slowly in deuterated media than in buffer prepared with H₂O. These results, when combined, provide support for the view that polymer hydrolysis plays an important role in governing the erosion of assemblies fabricated from these degradable polymers. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5161–5173, 2006     

PAMAM dendrimers for efficient siRNA delivery and potent gene silencing

Genuine, nondegraded PAMAM dendrimers self-assemble with siRNA into nanoscale particles that are efficient for siRNA delivery and induce potent endogenous gene silencing.     

Core/shell Fe3O4 @SiO2 nanoparticles modified with PAH as a vector for EGFP plasmid DNA delivery into HeLa cells

Novel stable core/shell Fe(3)O(4)@SiO(2)/PAH nanoparticles are synthesized using 15 nm Fe(3)O(4) as the template that is modified with PAH. The resulting nanoparticles can absorb plasmid DNA to mediate gene transfer in cultured HeLa cells. An electrophoretic assay suggests that the Fe(3)O(4)@SiO(2)/PAH nanoparticles protect the plasmid DNA from serum and DNase I degradation. A cell viability assay shows that the Fe(3)O(4)@SiO(2)/PAH nanoparticles exhibit a low cytotoxicity toward endothelial cells. Qualitative analysis of transfection in HeLa cells by nanoparticles carrying a plasmid DNA encoding EGFP demonstrates a fairly high expression level, even in the presence of serum. Thus, Fe(3)O(4)@SiO(2)/PAH nanoparticles are biocompatible and suitable for nonviral delivery, and may find applications in cancer therapy.     

非病毒性基因载体的合成研究

基因治疗是一种有效的治疗先天性遗传性疾病以及后天获得性疾病的手段。它通过激发细胞的生物活性或者抑制细胞非正常的功能来治疗或者预防疾病的发生,例如细胞的基因紊乱,细胞的无序增殖。目前基因治疗所面临的问题是缺乏有效的基因递送载体。基因载体主要分为病毒性基因载体和非病毒性基因载体。与病毒性基因载体相比,非病毒性基因载体具有毒性小、安全性高、易于制备、能够荷载分子量大的DNA等优点。本文综述了非病毒性基因载体的合成研究进展。     

Polyphosphonium polymers for siRNA delivery: an efficient and nontoxic alternative to polyammonium carriers

A water-soluble polyphosphonium polymer was synthesized and directly compared with its ammonium analog in terms of siRNA delivery. The triethylphosphonium polymer shows transfection efficiency up to 65% with 100% cell viability, whereas the best result obtained for the ammonium analog reaches only 25% transfection with 85% cell viability. Moreover, the nature of the alkyl substituents on the phosphonium cations is shown to have an important influence on the transfection efficiency and toxicity of the polyplexes. The present results show that the use of positively charged phosphonium groups is a worthy choice to achieve a good balance between toxicity and transfection efficiency in gene delivery systems.     

A reactive oxygen species-responsive dendrimer with low cytotoxicity for efficient and targeted gene delivery

Nonviral vectors have been attracting more attention for several advantages in gene delivery and the development of nonviral gene ca rriers with high delivery efficiency and low cytotoxicity has long been a key project.Starburst polyamidoamine dendrimers are a class of synthetic polymers with unique structural and physical characteristics.However,when they are used as gene carrier,the gene transfection efficiency is not satisfactory.Herein,a novel thioketal-core polyamidoamine dendrimer(i.e.,ROS...     

A supramolecular approach to the preparation of charge-tunable dendritic polycations for efficient gene delivery

A facile supramolecular approach for the preparation of charge-tunable dendritic polycations, by a combination of the multi-functionality of dendritic polymers with the dynamic-tunable ability of supramolecular polymers, has been developed. It provides a new strategy for designing and developing efficient gene vectors via noncovalent interactions.     

Fully charged: Maximizing the potential of cationic polyelectrolytes in applications ranging from membranes to gene delivery through rational design

Polyelectrolytes have found utility across various applications in materials science, from electrochemical devices to biotechnology, due to their facile processing and tunable properties. Through chemistry, rational manipulation of molecular structure enables individual families of polyelectrolytes to be used in emerging advanced applications. In this perspective, we focus on cationic systems, and we describe how various structural motifs influence macromolecular properties for anion exchange membranes and gene delivery vectors. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3167–3174