Phosphate‐Loaded Hydrogel Nanoparticles for Sepsis Prevention Prepared via Inverse Miniemulsion Polymerization

Local depletion of intestinal phosphate triggers changes in bacterial phenotypes that adversely affect the health of the host. This article describes a process for encapsulating phosphates in crosslinked poly(ethylene glycol) diacrylate (PEGDA) nanoparticles using inverse miniemulsion polymerization as a drug delivery approach for sustained release of phosphates to the intestinal epithelium. The effects of crosslinker, PEGDA co‐monomer, N‐vinyl pyrrolidone, (NVP) and surfactant concentrations on the nanoparticle size distribution, swelling ratio and monomer conversion are investigated. Increased surfactant and PEGDA concentrations result in smaller particle size and swelling ratio. A copolymerization model of crosslinking is used to predict conversion and gelation dynamics as a function of polymerization conditions. The model assumes that bulk polymerization can be used to approximate inverse miniemulsion polymerization with an aqueous‐phase initiator. The initiator efficiency is used as an adjustable parameter to simulate the conversion dynamics, thus accounting for radical confinement effects and interaction with emulsifier molecules.     

High Molecular Weight Poly(butyl methacrylate) via ATRP Miniemulsions

Summary: The reverse atom transfer radical polymerization of butyl methacrylate in miniemulsion, initiated with the redox pair hydrogen peroxide/ascorbic acid and mediated with copper(II) bromide tris[2-di(2-ethylhexyl acrylate)aminoethyl]amine is capable of producing well-controlled high-molecular weight poly(butyl methacrylate).     

Synthesis of Polyphosphate‐Loaded Nanoparticles Using Inverse Miniemulsion Polymerization for Sustained Delivery to the Gastrointestinal Tract

Polyphosphate salts, such as sodium hexametaphosphate (PPi), are effective in the attenuation of collagenase and biofilm production and prevention of anastomotic leak in mice models. However, systemic administration of polyphosphate solutions to the gut presents a series of difficulties such as uncontrolled delivery to target and off‐site tissues. In this article a process to produce PPi‐loaded poly(ethylene glycol) diacrylate (PEGDA) hydrogel nanoparticles through miniemulsion polymerization is developed. The effects of using a polyphosphate salt, as compared to a monophosphate salt, is investigated through cloud point measurements, which is then translated to a change in the required HLB of the miniemulsion system. A parametric study is developed and yields a way to control particle swelling ratio and mean diameter based on the surfactant and/or initiator concentration, among other parameters. Finally, release kinetics of two different crosslink density particles shows a sustained and tunable release of the encapsulated polyphosphate.     

基于细乳液聚合的纳米颗粒制备与应用研究进展-撤稿（Withdrawed）

细乳液聚合能够将多种材料封装在聚合物壳层中形成结构复杂的聚合物纳米颗粒。 与普通乳液聚合技术相比,细乳液聚合具有方便、环保、粒径可控、稳定性高等优点。 通过引入功能单体,可以很容易地实现对纳米颗粒的功能化。 目前,细乳液聚合技术已经应用于很多领域,如纺织颜料的合成、粘接剂、分子印迹、磁性靶向纳米颗粒等。 本文综述了近年关于细乳液聚合法合成纳米颗粒的各种应用。     

Fundamentals of RAFT Miniemulsion Polymerization Kinetics

Summary: The polymerization rate of RAFT-mediated miniemulsion polymerization, in which the time fraction of active radical ϕ_A is larger than a few percent, basically increases with reducing the particle size. For smaller particle sizes, however, the statistical variation of monomer concentration among particles may slow down the polymerization rate. The rate retardation by increasing the RAFT concentration occurs with or without the intermediate termination in a zero-one system. According to the present theoretical investigation, smaller particles are advantageous in implementing a faster polymerization rate, a narrower MWD, and a smaller number of dead polymer chains.     

Preparation of PMMA Nanoparticles Loaded with Benzophenone-3 through Miniemulsion Polymerization

Summary: The present paper analyzes the production of poly(methyl methacrylate) – PMMA – nanoparticles loaded with benzophenone-3 through miniemulsion polymerization. The obtained product is homogeneous and stable, allowing for preparation of photo-protective formulations. It is observed in particular that bezophenone-3 interacts with the reacting system, promoting the growth of the PMMA chains produced in miniemulsion.     

The Preparation of PVAc with Lower PDI Through RATRP in Miniemulsion Polymerization

In this paper, reverse atom transfer radical polymerization (RATRP) was used to prepare polyvinyl acetate (PVAc) with lower polydispersity index (PDI). The different reaction parameters such as ligand, catalyst, and surfactant were studied separately to control the polymerization of VAc. The results show that RATRP is not controlled with bpy as ligand, but it is possible to obtain PVAc with low PDI when PMDETA was used as ligand. The molecular weight and the PDI is 10.71×10⁴ and 1.62 when the molar ratio of AIBN/CuCl₂/PMDETA is 1.5:1:2, the molar ratio of AIBN to VAc is 0.5%, surfactant to deionized water is 10 wt%. The molecular weight and the PDI is 12.81×10⁴ and 1.48 when the molar ratio of AIBN/CuCl₂/PMDETA is 2:1:2. The structure of the polymer and the polymer conversion were investigated through ¹H-NMR and gravity method separately. The molecular weight (Mn) and the polydispersity of the obtained polymers were characterized through gel permeation chromatography (GPC).     

Preparation of Size Tunable Amphiphilic Poly(amino acid) Nanoparticles

Size tunable amphiphilic NPs composed of poly(γ‐PGA) and hydrophobic amino acids, such as Phe or Trp, were prepared. To prepare these size‐regulated NPs, γ‐PGA‐g‐Phe or γ‐PGA‐g‐Trp dissolved in DMSO was added to various concentrations of NaCl solution. The γ‐PGA‐Phe and γ‐PGA‐Trp formed monodispersed NPs, and the size of NPs can be easily controlled by NaCl concentration. The different‐sized NPs showed the same structure. The encapsulation of protein into the different‐sized NPs was successfully achieved and the size of protein‐encapsulated γ‐PGA‐Phe NPs was increased when protein was encapsulated.

     

Particle Size Effects in TEMPO‐Mediated Radical Polymerization of Styrene in Aqueous Miniemulsion

Summary: 2,2,6,6‐Tetramethylpiperidinyl‐1‐oxy (TEMPO)‐mediated radical polymerization of styrene in aqueous miniemulsion at 125 °C using sodium dodecylbenzenesulfonate and poly(vinyl alcohol), respectively, as colloidal stabilizers has been investigated. The particle size had a dramatic effect on the polymerization process. Decreasing particle size led to a markedly higher polymerization rate, but less control and a lower degree of livingness. For particles with diameters greater than approximately 170 nm, the polymerization behavior was essentially the same as in the corresponding bulk system. By varying the particle size within an appropriate range, it is possible to tune the polymerization such that the polymerization rate is increased while still maintaining reasonable control and livingness.

     

分散聚合法制备聚苯乙烯-铝纳米粒子复合材料

采用分散聚合法成功合成了高掺杂、窄分子量分布的聚苯乙烯-铝纳米粒子（PS-AlNPs）复合材料。采用XRD、FT-IR、GPC、TGA、SEM和TEM等手段对产物的晶体结构、分子结构、PS基体的分子量及分子量分布、热稳定性及形貌等进行了分析测试。结果表明：所得球形复合材料的平均粒径约为1.5μm,聚合过程中AlNPs的晶体结构未见变化,AlNPs掺杂量可高达1.81%,PS基体重均分子量达1.98×105,分子量分布指数为1.21,热稳定性优异。     

Solvent Effect in PLA-PEG Based Nanoparticles Synthesis through Surfactant Free Polymerization

Summary: In this work one-pot synthesis of PEGylated PLA-based nanoparticles (NPs) without using any surfactant has been performed. Adopting ring opening polymerization of L,L–Lactide and 2-hydroxyethyl methacrylate (HEMA), vinyl end functionalized poly(lactic acid) macromonomers (HEMA-LA_n) have been produced with tunable number of lactic acid units (larger than 5) and a low molecular weight distribution. Macromonomers have been further copolymerized with modified PEG chains (HEMA-PEG_m) through a monomer starved semi-batch emulsion polymerization performed without using any surfactant. In these conditions, small and monodispersed NPs of around 150 nm are obtained. Since macromonomers with n larger than 5 are highly viscous at room temperature, they have to be dissolved in a solvent before their injection in the reactor. In this work the effects in changing the solvent adopted in the starved process (water miscible or non-miscible) and its amount have been investigated. Moreover, the effect of both PEG chains concentration and MW on the final NPs properties has been elucidated. The colloidal stability of the NPs produced using different solvents has been verified in phosphate buffered saline (PBS) solution via dynamic light scattering measurements; in addition the critical coagulation concentration of these PEGylated NPs has been determined.     

Poly(glycoamidoamine)s: Cationic glycopolymers for DNA delivery

Polymer science is playing an exciting role in inspiring and advancing novel discoveries in the area of genetic drug delivery. Polymeric materials can be synthesized and chemically tailored to bind and compact nucleic acids into viral‐like nanoparticles termed polyplexes that can deliver genetic materials into cells. This article highlights our work in this area to synthesize and study a novel class of cationic glycopolymers that we have termed poly(glycoamidoamine)s (PGAAs). The design of these materials has been inspired by many previous works in the literature. Carbohydrate comonomers have been incorporated into these structures to lower the toxicity of the delivery vehicle, and oligoamine moieties have been added to yield a cationic backbone that facilitates strong DNA binding, compaction, cellular uptake, and delivery of genetic material. PGAAs have been designed to vary in the carbohydrate size, the hydroxyl number and stereochemistry, the amine number, and the presence or absence of heterocyclic groups. Through structure–bioactivity studies, we have discovered that these materials are highly biocompatible, and each specific feature plays a large role in the observed delivery efficacy. Such structure–property studies are important for increasing our understanding of how the polymer chemistry affects the biological activity for the clinical development of polymer‐based therapeutics. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6895–6908, 2006     

Poly(ethylene carbonate) Nanoparticles as Carrier System for Chemotherapy Showing Prolonged in vivo Circulation and Anti‐Tumor Efficacy

The aim of this study is to investigate the feasibility and efficacy of PEC nanoparticles as delivery system for cancer chemotherapy. Assembly of paclitaxel‐loaded nanoparticles with high loading efficiency and narrow‐size distribution is successful. For non‐invasive in vivo tracing, nanoparticle blends of chelator bearing poly(lactide) with PEC and PLGA are successfully prepared. Pharmacokinetic studies in mice reveal a twofold higher circulation time of PEC as compared to PLGA. A tumor model shows an accumulation of PEC NPs in cancerous tissue and a higher anti‐tumor efficiency compared to the standard Taxol?, which is reflected in a significantly slower tumor growth compared to the NaCl control group.

     

Synthesis and In-vitro drug release of insulin-loaded poly(n-butyl cyanoacrylate) nanoparticles

Nanoparticles have been prepared by dispersion polymerisation of n-butyl cyanoacrylate in acidified water, with and without the inclusion of insulin. The molecular weight of the polymerising material increases by a stepwise process, in which chains are initiated, terminated, and reinitiated, until an equilibrium molecular weight is reached. This equilibrium molecular weight is higher at lower dispersion pH. The reaction is complete within two hours. Insulin is capable of initiating polymerisation, but if introduced after all of the monomer has been incorporated into the growing nanoparticles it has no effect on polymer molecular weight. A drug loading of 72% was achieved in particles produced at 25 °C and pH 3.0, with insulin introduced one hour after monomer initiation. Particle degradation characteristics were assessed using solutions of esterase in phosphate buffered saline at pH 7.0, with butanol release monitored as a measure of polymer degradation. Insulin release was monitored under the same conditions. Both butanol production and insulin release showed a similar biphasic mechanism, indicating that the drug release rate is determined by polymer degradation characteristics. An initial burst release of both materials is associated with the degradation of surface species, and this is then followed by a steady-state release from sub-surface material.

Insulin release as a function of time at an esterase concentration of 2.0 mg · ml⁻¹.     

Production of PMMA Nanoparticles Loaded with Praziquantel Through “In Situ” Miniemulsion Polymerization

PZQ is the primary drug for treatment of schistosomiasis, but its efficiency is severely affected by its bitter taste. The main objective of this paper is the preparation of PMMA nanoparticles loaded with PZQ through in situ miniemulsion polymerizations and intended for oral formulations. Polymerizations are performed with an ultra turrax and a high‐pressure homogenizer. Obtained nanoparticles are analyzed by DSC, HPLC, DLS, GC, SEM, and PZQ dissolution profiles. Obtained results indicate the successful encapsulation of PZQ in all runs. Obtained data also show that the high‐pressure homogenizer leads to the best performance, allowing for preparation of stable latexes, with narrower particle size distributions and higher encapsulation efficiencies.

     

Poly (methacrylic acid)‐based molecularly imprinted polymer nanoparticles containing 5‐fluourouracil used in colon cancer therapy potentially

The objective of this work was to synthesize molecularly imprinted polymer (MIP) nanoparticles based on methacrylic acid (MAA) monomer with a high selectivity against an anti‐cancer drug, 5‐fluorouracil (5‐FU), as a template. In this case, the nanoparticles were prepared via precipitation polymerization in the presence of ethylene glycol dimethacrylate as cross‐linker and azobisisobutyronitrile as initiator. Besides, 3 independent variables including MAA: 5‐FU molar ratio (X₁), temperature (X₂), and time (X₃) were investigated utilizing response surface methodology. The scanning electron microscopy and dynamic light scattering resulted the average diameter of approximately 65 nm, and the MIP nanoparticle sample with the imprinting factor of 1.57 was polymerized in optimized conditions as follows: X₁ = 6: 1, X₂ = 60°C, and X₃ = 3 days in acetonitrile as porogenic solvent. Also, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis confirmed the formation of MAA/5‐FU complex and lower thermal stability of the washed MIP sample than the unwashed MIP and non‐imprinted polymer (NIP) samples, respectively. Moreover, the optimized MIP nanoparticles have more controlled release of 5‐FU rather than the NIP sample. Finally, the flow cytometry showed that 5‐FU‐loaded MIP sample has the highest apoptosis of human colon cancer cell line, HCT‐116, after 3 days compared with NIP sample and also the exclusive use of drug.