Core-shell nanohydrogel structures as tunable delivery systems

Poly(acrylonitrile-co-N-isopropylacrylamide) (p(AN-co-NIPAM)) core-shell hydrogel nanoparticles were synthesized by microemulsion polymerization and their feasibility as a drug carrier was investigated. Highly monodispersed nanoparticles with desired size range - i.e., 50-150 nm - were prepared by adjusting the reaction conditions. The hydrophobic core of the composite which consists primarily of poly(acrylonitrile), can be easily made highly hydrophilic by converting the nitrile groups to the corresponding amidoxime groups. This provides a level of tunability in the hydrophobicity/hydrophilicity balance of the composite nanoparticle. The thermo-responsive feature of the shell was utilized for the release of a model drug, propranolol (PPL). It is shown that the loading/release capacity of nanoparticles was increased almost two-fold by the amidoximation of the core material.  

Pulsed electron beam irradiation of dilute aqueous poly(vinyl methyl ether) solutions

A dilute aqueous solution of the temperature-sensitive polymer, poly(vinyl methyl ether) (PVME), was irradiated by a pulsed electron beam in a closed-loop system. At temperatures, below the lower critical solution temperature (LCST), intramolecular crosslinked macromolecules, nanogels, were formed. With increasing radiation dose D the molecular weights M_w increase, whereas the dimensions (radius of gyration R_g, hydrodynamic radius R_h) of the formed nanogels decrease. The structure of the PVME nanogels was analyzed by field emission scanning electron microscopy (FESEM) and globular structures with d=(10-30) nm were observed. The phase-transition temperature of the nanogels, as determined by cloud point measurements, decreases from T_cr=36 °C (non-irradiated polymer) to T_cr=29 °C (c_p=12.5 mM, D=15 kGy), because of the formation of additional crosslinks and an increase in molecular weights. The same behavior was observed for a pre-irradiated PVME (γ-irradiation) with higher molecular weight due to intermolecular crosslinks. After pulsed electron beam irradiation the molecular weight again slightly increases whereas the dimension decreases. Above D=1 kGy the calculated ρ-parameter (ρ=R_g/R_h) is in the range of ρ=0.5-0.6 that corresponds to freely draining globular structures.  

pH-sensitive nanogels based on Boltorn H40 and poly(vinylpyridine) using mini-emulsion polymerization for delivery of hydrophobic anticancer drugs

In this study, we describe the synthesis of a new structure of pH-sensitive H40 based nanogel by click reaction through mini-emulsion polymerization. The nanogels were synthesized by cross coupling of H40-poly(ε-caprolactone) (H40-PCL) dendrimers as cores and poly(vinylpyridine) (PVP) as a pH sensitive crosslinker. The poly(ethylene glycol) (PEG) pendant group was introduced at the middle of PVP chains as hydrophilic segment to act as hydrophilic shell at final nanogel for better dispersity. Folic acid that is conjugated at the end of some of PEG through the free carboxyl group was used for targeting cancer cells that overexpress folate receptors.  

One-pot synthesis of amphiphilic nanogels from vinylated SPIONs/HEMA/PEG via a combination of click chemistry and surfactant-free emulsion photopolymerization: Unveiling of the protein-nanoparticle interactions

In this study, freshly prepared Fe₃O₄ nanoparticles (MNP1) were coated with 3-aminopropyltriethoxysilane (APTES) to produce core–shell Fe₃O₄@SiO₂ nanoparticles (MNP2), amine terminated nanoparticles was converted into the triazide in the presence of as-prepared triflic azide (MNP3). Propargyl acrylate (PgA) was synthesized from propargyl alcohol and acryloyl chloride and their structures were characterized by FT-IR and ¹H NMR spectroscopy. MNP3 were modified by PgA via click reaction to produce fully decorated triazole product (MNP4). Photopolymerization of MNP4 in the presence of hydroxyethyl methacrylate (HEMA) and acrylated methyl ether poly (ethylene glycol) (ACMPEG) were carried out by emulsion method without any surfactant (MNP5). The in-vitro release behavior of quercetin from MNP5s was investigated at two pHs (7.4 and 5.8). The effect of fetal bovine serum (FBS) on MNPs and its ability to cover magnetite nanoparticles was investigated.  

Nanogel-modified polycaprolactone microfibres with controlled water uptake and degradability

In this work we prepared composite poly(caprolactone) (PCL) microfibres decorated with temperature-sensitive poly(N-vinylcaprolactam) nanogels by an one-step electropsinning process. Microfibres with variable internal structure were prepared by using two different solvent systems: methanol/toluene (Me/Tol) and chloroform/dimethylformamide (Ch/DMF). Our experimental data shows that the nature of the solvent mixtures allows obtaining microfibres with different morphologies: Microfibres with nanogels on the fibre surface (Me/Tol) and microfibres with nanogels in the fibre interior (Ch/DMF). The morphology of composite fibres was visualized by scanning electron microscopy (SEM) and their properties investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA) and contact angle measurements. The results show that combining hydrophobic poly(caprolactone) with hydrophilic nanogels leads to microfibres exhibiting controlled swelling in water. Additionally, the thermo-sensitive properties of the nanogels are maintained whether they are on the surface or inside of the fibres. The presence of nanogels in the fibre structure also allows regulating their degradability.  

Soft and flexible hydrogel templates of different sizes and various functionalities for metal nanoparticle preparation and their use in catalysis

Hydrogels are important functional materials with a myriad of potential applications. As the chemically stable and interlocked polymeric network retains vast amounts of water without dissolving, the use of hydrogel matrices for preparation of metal nanoparticles in situ is feasible, and readily applicable in the catalysis of various aquatic and non-aquatic reactions. The functional groups in the hydrogel network can act as both chelating and capping agents for metal nanoparticle preparation from metal ions and for their stabilization; thus, the metal particles are protected from the atmosphere hindering the oxidation/deactivation and aggregation, allowing an increase in their stability and longevity. The functional groups binding ability in hydrogel matrices allow metal ions with different oxidation state such as Fe, Co, Ni, Cu, Ru, Au and so on, to be loaded into the hydrogel matrices. Then, these metal ions can be reduced/precipitated to their metallic particle forms inside hydrogels of different dimensions using green chemicals (those with no hazardous impact on the environment) or non-toxic chemical reducing agents such as NaBH₄, H₂, citrate, ethylene glycol, etc., depending upon the nature of the metal ions. The hydrogel-supported metal nanoparticles can be successfully used for the reduction of nitro compounds, hydrolysis of various hydrides and degradation of toxic species such as dyes, chlorohydrocarbons, pesticides, insecticides and so on. In this review, a flexible and highly adaptable platform for the design of soft and versatile interfaces with an outlook toward their use in material science, engineering and catalysis for in situ metal nanoparticle preparation within hydrogels for the catalysis purpose is addressed. In addition, even ex situ prepared metal nanoparticles can be readily incorporated within hydrogel matrices for various purposes are considered. The techniques outlined here afford robust hydrogel–metal composite systems with excellent control over size, composition and topography of the interfaces. Further directions from soft and flexible reactor of polymeric network at various dimensions, providing a continuously and environmentally workable milieu for designing and developing advanced technology are also addressed.  

水溶性丁二酸酐酰化壳聚糖纳米凝胶的制备及其pH 响应性研究

以水为介质、碳酸钠为催化剂，室温下制备了水溶性丁二酸酐酰化壳聚糖，研究了反应物料比对产物酰化取代度及水溶性的影响。红外光谱分析表明丁二酸酐成功接枝到了壳聚糖分子链上；XRD 结果表明酰化反应改变了壳聚糖的结晶结构；Zeta 电位分析发现存在1个等电点：pI＝3.54。将丁二酸酐酰化壳聚糖加入到甲酸溶液中，通过自组装法制备纳米凝胶粒子。SEM 照片显示该纳米凝胶粒子呈球形，粒径为20～30 nm；DLS 测试表明，随溶液 pH 值的增大，粒径从70～80 nm 增大到350～700 nm，表明丁二酸酐酰化壳聚糖纳米凝胶粒子具有一定的 pH 响应性。  

Aqueous nanogels modified with cyclodextrin

In this work, the incorporation of reactive cyclodextrins (CDs) in aqueous nanogels based on poly(N-vinylcaprolactam) (VCL) is studied by surfactant-free precipitation polymerization process. α-, β-, γ-CDs were functionalized with acrylic groups and the average amount of vinyl bonds per CD molecule was adjusted to 2, 4, or 6. The increase of the CD concentration in the reaction mixture led to the reduction of the final hydrodynamic radius of nanogels from 227 nm to 62 nm. The increase of the vinyl groups number per CD molecule induced formation of smaller nanogels (R_h = 22.5 nm) and considerable increase of the crosslinking degree. Obtained cyclodextrin-modified nanogels show temperature sensitivity in aqueous medium with a volume transition point around 30 °C. The complexation properties of CDs incorporated in nanogel networks were proved by titration with phenolphthalein.  

Radiation-induced synthesis of poly(vinylpyrrolidone) nanogel

Studies of the radiation-induced synthesis of poly(vinylpyrrolidone) (PVP) nanogels, intended to provide a basis for obtaining intra-molecular cross-linked products, which are more useful in drug delivery, show that a sharp change in the controlling mechanism from inter-molecular to intra-molecular cross-linking occurs above a threshold temperature around 50 °C-55 °C, even though the rate of inter-molecular cross-linking is enhanced as the temperature is raised. When aqueous solutions of PVP are irradiated, the activation energy of the decay of the PVP· radical is observed to rise sharply above this threshold temperature. This can be attributed to the collapse of the polymer chains, which occurs at temperatures above approximately 55 °C and leads to a reduction of the R_h of the irradiated polymer molecules at 77 °C to (44 ± 3) % of that of PVP molecules that were not irradiated at 20 °C, as shown by the results of AFFFF measurements. The abrupt transition to a mechanism controlled by intra-molecular cross-linking is due to the thermal collapse of the polymer structure. This accounts for the observation that activation energy is higher within the temperature range above 55 °C. Higher pulse repetition rates during electron irradiation also promote intra-molecular cross-linking.  

Fabrication of core or shell reversibly photo cross-linked micelles and nanogels from double responsive water-soluble block copolymers

Poly(butanedioic acid, 1-[3-[(2-methyl-1-oxo-2-propen-1-yl)oxy]propyl] ester)-b-poly(methoxydi(ethylene glycol) methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy] coumarin) (PSPMA-b-P(DEGMMA-co-CMA)) block copolymer was synthesized via atom transfer radical polymerization (ATRP). The temperature and pH responsive micellization behaviors of PSPMA-b-P(DEGMMA-co-CMA) were investigated to obtain P(DEGMMA-co-CMA)-core and PSPMA-core micelles. After the two types of micelles were exposed to 365 nm UV light, core cross-linked (CCL) micelles and shell cross-linked (SCL) micelles were facilely prepared. The photo cross-linking was proved to be reversibly controlled under alternative irradiation of 365 nm and 254 nm UV light. More interestingly, block copolymer nanogels were fabricated by translating the hydrophobic core of the CCL and SCL micelles into hydrophilic via adjusting the temperature and pH. The sizes of the block copolymer nanogels can be facilely controlled by UV light irradiation. The introduction of reversibly photo cross-linkable groups into the double responsive block copolymers provides a novel approach to develop more sophisticated, controllable, and smarter nanocarriers that might have great potentials in biomedical applications.