Aminoethyl Methacrylate Research Articles

Gradient Functionalization of Poly(lactic acid)-Based Materials with Polylysine for Spatially Controlled Cell Adhesion.

The development of biomaterials with gradient surface modification capable of spatially controlled cell adhesion and migration is of great importance for tissue engineering and regeneration. In this study, we proposed a method for the covalent modification of PLA-based materials with a cationic polypeptide (polylysine, PLys) via a thiol-ene click reaction carried out under a light gradient. With this aim, PLA-based films were fabricated and modified with 2-aminoethyl methacrylate (AEMA) as a double bond source. The latter was introduced by reacting pre-formed and activated surface carboxyl groups with the amino group of AEMA. The success of the modification was confirmed by 1H NMR, Raman and X-ray photoelectron spectroscopy data. A further photoinduced thiol-ene click reaction in the presence of a photosensitive initiator as a radical source was further optimized using cysteine. For grafting of PLys via the thiol-ene click reaction, PLys with a terminal thiol group was synthesized by ring-opening polymerization using Cys(Acm) as an amine initiator. Deprotection of the polypeptide resulted in the formation of free thiol groups of Cys-PLys. Successful gradient grafting of Cys-PLys was evidenced by covalent staining with the fluorescent dye Cy3-NHS. In addition, PLys gradient-dependent adhesion and migration of HEK 293 cells on PLys-PLA-based surfaces was confirmed.

Preparation and Characterization of Photo-Cross-Linkable Methacrylated Silk Fibroin and Methacrylated Hyaluronic Acid Composite Hydrogels.

Composite biomaterials with excellent biocompatibility and biodegradability are crucial in tissue engineering. In this work, a composite protein and polysaccharide photo-cross-linkable hydrogel was prepared using silk fibroin methacrylate (SFMA) and hyaluronic acid methacrylate (HAMA). SFMA was obtained by the methacrylation of degummed SF with glycidyl methacrylate (GMA), while HA was methacrylated by 2-aminoethyl methacrylate hydrochloride (AEMA). We investigated the effect of the addition of 1 wt % HAMA to 5, 10, and 20 wt % SFMA, which resulted in an increase in both static and cycling mechanical strengths. All composite hydrogels gelled under UV light in <30 s, allowing for rapid stabilization and stiffness increases. The biocompatibility of the hydrogels was confirmed by direct and indirect contact methods and by evaluation against the NIH3T3 and MC3T3 cell lines with a live-dead assay by confocal imaging. The range of obtained mechanical properties from developed composite and UV-cross-linkable hydrogels sets the basis as possible future biomaterials for various biomedical applications.

Fabrication of an IgG-imprinted monolith micro-solid phase extraction chip for IgG extraction from human plasma

Molecular imprinted polymers (MIPs), also known as synthetic antibodies, offer a novel and promising approach for protein separation at analytical scale. In proteomics research, this approach could capture target high abundant proteins from biological fluids to reduce sample complexity. In this study, we have explored the potential to imprint human immunoglobulin G (IgG) to develop a micro-solid phase extraction chip for selective removal of IgG from human plasma. Imprinting of IgG within the polyhydroxy ethyl methacrylate monolith containing dimethyl amino ethyl methacrylate (DMAEMA) as a functional monomer was successfully achieved and characterized using FT-IR spectroscopy and protein assay kit. 0.1 M tris buffer (pH 7) and UV-polymerization were identified as the ideal buffer and polymerization strategy to imprint IgG within 30 min. Template (IgG) elution using 10 % acetic acid containing 10 % (v/v) SDS as elution buffer was moderately successful (25 % IgG-template free monolith was obtained). Protein shape has influenced its imprinting and elution from the monolith. The protocol developed to imprint one protein cannot be translated to another protein without further modifications. A 10-fold decrease of DMAEMA concentration within the monolith and a sequential elution step has resulted in >90 % IgG-template free monolith. The IgG-template free monolith has displayed an adsorption capacity of ∼ 3.7 mg per g monolith and showed good IgG selectivity as compared to other tested human proteins (human serum albumin, transferrin and fibrinogen). Translation of imprinted monolith protocol to develop a micro-solid phase extraction chip was successful. The chip can be re-used for 5 cycles with >95 % reusability and has selectively captured IgG from human plasma.

Ultrasound-assisted dispersive micro solid phase extraction of maneb in water and food samples with new hybrid block copolymer material prior to micro-spectrophotometric analysis

A simple and effective ultrasound-assisted dispersive micro solid-phase extraction (UA-dμSPE) method was developed for the spectrophotometric determination of traces maneb in food and water. In this study, a new hybrid block copolymer poly (vinyl benzyl chloride-b-dimethyl aminoethyl methacrylate) (Pvb-DMA) was synthesized and characterized using techniques such as FTIR, SEM-EDX. The synthesized Pvb-DMA was used as an adsorbent for the extraction of maneb for first time in this study. The effects of different experimental variables such as pH, adsorbent amount, sample volume, eluent type were optimized. The statistical toll factorial design was applied to estimate the individual and combined impact of parameters on the extraction of maneb. The applicability of different solvents such as acetone, methanol, ethanol, tetrahydrofuran, acetonitrile for maneb recovery from adsorbent was tested. The detection and quantification limits were found to be 3.3 ng mL−1 and 10.0 ng mL−1, respectively. In addition, the preconcentration factor and linear range was obtained 300 and 10–500 ng mL−1. The extraction recovery and relative standard deviation were found to be 95 % and 2.8 %, respectively.

Synthesis of multi-stimuli-responsive flocculants using reversible addition-fragmentation chain transfer polymerization: Investigating the performance and mechanism of kaolin coagulation

Coumarin-containing amphiphilic block copolymers with different compositions, as a new class of pH- and photo-responsive flocculants, were synthesized through reversible addition-fragmentation chain transfer polymerization of dimethyl aminoethyl methacrylate (DMAEMA), methyl methacrylate, and 7-acryloyloxy 4-methylcoumarin. Proton nuclear magnetic resonance spectroscopy was used to study the structure and composition of the copolymers. Zeta potential results show that the copolymers are applicable as amphoteric flocculants. The optimal flocculant concentration was calculated using the Jar analysis for kaolin flocculation, and the results show that the flocculation dependence on the flocculent concentration decreases with increasing its molecular weight. The dominance of charge neutralization in the flocculants with lower molecular weights and the dominance of adsorption bridging and hydrophobic association in the flocculants with higher molecular weights were indicated. These results are in agreement with the rheological data. To investigate the governing mechanism more precisely, the flocculation rate was calculated using turbidity measurements at different pH values over time. The highest final flocculation rate (99.25 %) corresponds to pH 4.5, which caused by the protonation of the amine groups of the DMAEMA repeating units. The dependence of settling rate on pH indicates the pH-dependent performance of the flocculants. Finally, fluorescence microscopy image of the flocculants shows its proper functioning of in the vicinity of kaolin, which has a promising industrial application.

ZIF-8-mediated block copolymer micelles and its application in drug delivery

Block copolymer micelles have been widely used in drug delivery. Great efforts have been made to optimize the function of block copolymer micelles and further enhance their bioavailability. We propose a means of embedding ZIF-8 in block copolymer micelles to regulate its stability for improving the drug release kinetics. The block copolymer poly (2-(diisopropyl amino-ethyl methacrylate)-block-poly (vinylimidazole-co-poly (ethylene glycol) methyl methacrylate) (PDPA18-b-P(Vim18-co-P(EG)5MA21) (PDPV) bearing imidazole moiety was synthesized through reversible addition-cracking chain transfer (RAFT) polymerization. PDPV can self-assemble into micelles in aqueous solution and then be loaded with doxorubicin (DOX) to obtain DOX@PDPV, followed by Zn coordination to anchor ZIF-8 to the PVim moiety in DOX@PDPV to obtain the final drug delivery system DOX@PDPV@ZIF-8 hybrids. The DOX@PDPV@ZIF-8 hybrids can avoid the influence of the critical micelle concentration (CMC) on it, which was further prevent the premature leakage of DOX under physiological conditions. Furthermore, the pH-responsive properties of PDPA and ZIF-8 facilitated enabled the effective release of DOX in weakly acidic tumor environments. In vitro studies also confirmed that DOX@PDPV@ZIF-8 improved DOX accumulation in cells, leading to the inhibition of cancer cell growth. Therefore, the integrated design provided a promising strategy to regulate the stability of block copolymer micelles, improve drug release kinetics, and ultimately inhibit the growth of cancer cell.

Acrylates and Methacrylates Sensitization in Patients with Orthopedic and Dental Prostheses: Asymptomatic Pre-Implant and Symptomatic Post-Implant Testing.

Acrylates and methacrylates are widely used in dental and orthopedic prostheses, false nails, adhesives, glues, and paints, and are strong sensitizers. The aim of our study was to assess the prevalence of acrylate sensitization in patients before the application of dental or orthopedic prostheses or after the application in case of potentially related contact dermatitis. Methods: The subjects were tested according to haptens reported in safety data sheets, including methyl methacrylate (MMA) 5%, methyl acrylate (MA) 1%, ethyl methacrylate (EMA) 2%, ethyl acrylate (EA) 1%, butylacrylate 0.1%, 2 hydroxyethyl methacrylate (HEMA) 5%, ethylene glycol dimethacrylate 2% (EGDMA), tetraethylene glycol dimethacrylate 2% (TEGDMA), and dimethyl amino ethyl methacrylate 0.2% (DAEMA). Multivariable logistic regression was used to study the factors associated with (meth)acrylate sensitization. Results: Six hundred sixty-five patients (75.4% of the total sample) without contact dermatitis before the placement of any dental or orthopedic prosthesis and 217 patients (24.6% of the total sample) with contact dermatitis potentially due to already placed prostheses were involved. In total, 37 cases of patch test positivity to at least 1 acrylate (4.2%) were found. In the pre-implant population, previous dermatitis and respiratory allergy were associated with increased sensitization to acrylates in multivariable regression analysis (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.05-5.39; OR 2.96, 95% CI 1.32-6.64, respectively). The prevalence of sensitization was 3.5% for EGDMA, 2.7% for EA, 1.5% for 2-HEMA, 1.4% for both MA and MMA, 1.28% for DAEMA, and 0.8% for EMA. No statistically significant difference was found in the prevalence of sensitization between the pre- and post-implant groups. Discussion: Our study found a similar profile of sensitization in pre-implant and post-implant patients, suggesting the need to better study the specificity and sensitivity of patch tests to (meth)acrylate and to define relevance considering a detailed history of exposure.

Fabrication of graphene oxide decorated with poly(dimethyl amino ethyl methacrylate) brush for efficient Cr(VI) adsorption from aqueous solution

Confronting the severe health threats and environmental impacts of Cr(VI) in aquatic environments demands innovative and effective remediation approaches. In this study, Graphene oxide (GO)-decorated poly(dimethyl amino ethyl methacrylate) (PDMAEMA) brush nanocomposites (GOP1, GOP2, GOP3, and GOP4) were fabricated using atom transfer radical polymerization (ATRP) by the “graft from” method. The resulting nanocomposites were utilized for removing Cr(VI) with good adsorption performance due to the electrostatic interaction of protonated nitrogen groups in the brush chains with negatively charged particles in the solution. The kinetic model of pseudo-second-order best represented the contaminants' adsorption characteristics. The Weber–Morris model further indicated that surface adsorption and intraparticle diffusion mechanisms primarily controlled the adsorption procedure. Additionally, the Langmuir and Temkin isotherm models were found to most accurately represent the adsorption characteristics of the pollutants on the nanocomposites, and GOP4 can achieve the maximum adsorption capacity of 164.4 mg·g–1. The adsorbents' capacity maintains above 85% after five cycles of adsorption-desorption. The nanocomposites in this study demonstrate promising potential for eliminating Cr(VI) from aqueous solutions.

Pharmacokinetic control of orally dosed cyclosporine A with mucosal drug delivery system.

This study aimed to control the oral absorption of cyclosporine A (CsA) with the use of a mucosal drug delivery system (mDDS). Mucopenetrating nanocarriers (MP/NCs) and mucoadhesive nanocarriers (MA/NCs) were prepared by flash nanoprecipitation employing polystyrene-block-poly(ethylene glycol) and polystyrene-block-poly(N,N-dimethyl aminoethyl methacrylate), respectively. Their particle distribution in the rat gastrointestinal tract were visualized by fluorescent imaging. Plasma concentrations were monitored after oral administration of CsA-loaded MP/NCs (MP/CsA) and MA/NCs (MA/CsA) to rats. MP/NCs and MA/NCs had a particle size below 200nm and ζ-potentials of 4 and 40mV, respectively. The results from in vitro experiments demonstrated mucopenetration of MP/NCs and mucoadhesion of MA/NCs. Confocal laser scanning microscopic images showed diffusion of MP/NCs in the gastrointestinal mucus towards epithelial cells and localization of MA/NCs on the surface of the gastrointestinal mucus layer. In a pH 6.8 solution, rapid and sustained release of CsA were observed for MP/CsA and MA/CsA, respectively. After oral dosing (10 mg-CsA/kg) to rats, amorphous CsA powder exhibited a time to maximum plasma concentration (Tmax) of 3.4h, maximum plasma concentration (Cmax) of 0.12μg/mL, and bioavailability of 0.7%. Compared with amorphous CsA powder, MP/CsA shortened Tmax by 1.1 to 2.3h and increased the bioavailability by 43-fold to 30.1%, while MA/CsA prolonged Tmax by 3.4 to 6.8h with Cmax and bioavailability of 0.65μg/mL and 11.7%, respectively. These pharmacokinetic behaviors would be explained by their diffusion and release properties modulated by polymeric surface modification. The mDDS approach is a promising strategy for the pharmacokinetic control of orally administered CsA.

Fabrication of pH-Responsive PDPAEMA Thin Film Using a One-Step Environmentally Friendly Plasma Enhanced Chemical Vapor Deposition

In recent years, there has been growing interest in pH-responsive polymers. Polymers with ionizable tertiary amine groups, which have the potential to be used in many critical application areas due to their pKa values, have an important place in pH-responsive polymers. In this study, poly(2-Diisopropyl aminoethyl methacrylate) (PDPAEMA) thin films were coated on various substrates such as glass, fabric, and silicon wafer using a one-step environmentally friendly plasma enhanced chemical vapor deposition (PECVD) method. The effects of typical PECVD plasma processing parameters such as substrate temperature, plasma power, and reactor pressure on the deposition rate were studied. The highest deposition rate was obtained at a substrate temperature of 40 °C, a reactor pressure of 300 mtorr, and a plasma power of 60 W. The apparent activation energy was found to be 17.56 kJ/mol. Based on the results of this study, uniform film thickness and surface roughness were observed in a large area. The PDPAEMA thin film was exposed to successive acid/base cycles. The results showed that the pH sensitivity of the thin film produced by the PECVD method is permanent and reversible.

Block sequence dependent self-assembly and optoelectronic behavior of thermo- and pH-sensitive Polythiophene-graft-[Poly(diethylene glycol methyl ether methacrylate)-block-Poly(dimethyl amino ethyl methacrylate)] copolymers

To overcome the difficulty of using multistep process we report an one pot synthesis of polythiophene (PT)-graft block copolymers with thermo-sensitive poly(diethyleneglycol methyl ether methacrylate)(PDEGMEM) and pH-sensitive poly(dimethyl amino ethyl methacrylate)(PDMAEMA) using ATRP technique. The polymers PT-g-(PDEGMEM10-b-PDMAEMA3) (P1), PT-g-(PDMAEMA10-b-PDEGMEM3) (P2) and PT-g-(PDMAEMA6-ran-PDEGMEM8) (P3) are characterized by 1H NMR and SEC techniques. HRTEM study shows that P1 and P3 exhibit micellar morphology but P2 shows vesicular morphology, all sizes increase with increasing pH and temperature. UV–vis absorption spectra show pH, temperature and sequence dependent absorbance peak, and dc-conductivity (P2 > P3 > P1) indicates semi-conducting nature. Current-Voltage (I-V) property shows pH dependent memory and OMEIC property following above order. At pH3, on irradiation with white light the photocurrent gains of P2, P3 and P1 are 7.9, 6.6 and 3.5, respectively. Thus PT-graft block copolymers exhibit tunable self-assembly, optoelectronic, transport and photocurrent properties depending on proximity and preponderance of block sequence from PT backbone and also for their pH and thermo-responsivity.

Aggregation-Induced Fluorescence Upconversion of Pyrene under Low Fluence: In Solutions and Polymeric Nanoparticles.

In this study, aggregation-induced photon upconversion (iPUC) is demonstrated in the small polyaromatic molecule, pyrene. In binary-solvent mixtures, water, which induces the aggregation of polyaromatic molecules, assisted in triplet-triplet annihilation-based upconversion. No upconverted emission was observed in a dry solvent. Although upconverted emission in the absence of a triplet sensitizer was assigned to pyrene-aggregate-induced sensitization, the presence of a triplet sensitizer enhanced the upconversion efficiency. This experimental finding was further simulated to explore the possibility of iPUC in the condensed-phase polymer matrix. We studied 2-aminoethyl methacrylate hydrochloride-polystyrene copolymer nanoparticles embedded with the molecular upconversion system. The nanoparticle iPUC agreed with the proposition that water domains were present in polymer nanoparticles and helped aggregate pyrene in the host polymer. Despite the low systemic upconversion efficiency, this study provides a method for achieving fluorescence upconversion in relatively simple systems.

Fabrication of antimicrobial cationic hydrogels driven by physically and chemically crosslinking for wound healing

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.

N,N-Dimethylaminoethyl methacrylate-based core/shell microgels loaded with silver nanoparticles for catalysis.

In this work, poly(styrene)@poly(N-isopropylmethacrylamide-co-2-(N,N-dimethyl)aminoethyl methacrylate [p(sty)@p(NIPMAM-DMAEMA)] core/shell microgel particles were produced by a two-step free-radical precipitation polymerization process. Ag nanoparticles were successfully embedded inside the sieves of a crosslinked network by using silver nitrate as the precursor salt and NaBH4 as the reductant. The synthesized pure and hybrid microgels were analyzed by various characterization tools, including Fourier transform infrared (FTIR) and UV-visible (UV-vis) spectroscopies, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Results indicate the successful fabrication of spherical silver nanoparticles with diameters ranging from 10 to 15 nm within the sieves of the poly(styrene)@poly(N-isopropylmethacrylamide-co-2-(N,N-dimethyl)aminoethyl methacrylate) core/shell microgels, which have a hydrodynamic diameter of 155 ± 25 nm. The Ag nanomaterial exhibited long-term stability in the p(sty)@p(NIPMAM-DMAEMA) system due to the strong donor-acceptor relationship between the lone pair of the amide moiety in the polymer microgels and the Ag nanomaterial. The catalytic activity of the Ag-p(sty)@p(NIPMAM-DMAEMA) material was determined by performing the catalytic reduction of p-nitrophenol (4-NPh) as a model reaction under diverse concentrations of the catalyst. UV-vis spectrophotometry was used to check the progress of the reaction. The apparent rate constant (k app) was measured by applying the pseudo-first-order kinetics model. It was observed that k app increased with increasing catalyst dose, demonstrating occurrence of the reaction on the surface of the catalyst.

A stiff and tough triple-shape memory hydrogel triggered at body temperature by hydrophobic association and electrostatic interaction

While triple-shape memory hydrogels (TSMHs) are considered promising materials for intelligent medical devices, obtaining TSMHs triggered at the human body temperature with adequate mechanical performance remains challenging. Herein, a stiff and tough TSMH with a wide glass transition temperature (Tg) range at approximately 36 °C is constructed by copolymerizing hydrophobic 2-aminoethyl methacrylate isopropyl carbamate (IMA) with zwitterionic sulfobetaine methacrylate (SBMA). While the introduction of SBMA into the poly(2-aminoethyl methacrylate isopropyl carbamate) (PIMA) polymer chain weakens the ultra-strong hydrophobic association, it causes an electrostatic interaction, which increases the flexibility of the copolymer chains and the cross-linking density of the network. Based on these structural characteristics, the poly(2-aminoethyl methacrylate isopropyl carbamate-co- sulfobetaine methacrylate) [P(IMA-co-SBMA)] hydrogels show reasonable triple shape memory effect with wide Tg ranging from 22 °C to 46 °C, Young's modulus from 2.82 MPa to 22.15 MPa, and fracture strain from 43 % to 444 %. This study provides a novel strategy for balancing the mechanical properties and Tg of TSMHs as materials for intelligent medical devices.

Scalable fabrication of amine-functionalized microgel composite membranes and their gas permeation characteristics

Post-combustion carbon dioxide (CO2) separation from exhaust gases is a bridge technology to reduce the emissions of traditional combustion processes. Primary amine-functionalized building blocks enhance the CO2 selectivity of membranes via a facilitated transport mechanism. Microgels are polymer-based colloids that can be functionalized with amine groups. However, to serve as a successful membrane building block, high aminesloading, and a scalable fabrication route are necessary. Here, we report the continuous synthesis of amine-functionalized microgels and apply them as a dense selectivity layer to form thin-film composite membranes (TFC). The synthesis process was successfully scaled up from batch to laminar flow reactor, producing microgels containing up to 50 mol% amine incorporation. Amine incorporation influences microgel water uptake important for their gas separation properties. Porous polyacrylonitrile (PAN) membranes containing a spray-coated microgel layer are tested using a mixture of CO2 and N2, with or without humidity in the feed stream. Both CO2 permeance and selectivity increase with the amine content in the microgels and the moisture in the feed stream. At 95% relative humidity, the CO2 permeance improved from 38 to 100 GPU when the amine incorporation rose from zero to 48% of 2-aminoethyl methacrylate (AEMA). The continuous synthesis allows large-scale fabrication of these microgels for applications such as membrane functionalization. Furthermore, the developed microgel-functionalized gas separation membranes are promising for CO2 removal applications from high-humidity streams, such as flue gas.

A novel block copolymer containing gadolinium oxide nanoparticles in ultrasound assisted-dispersive solid phase microextraction of total arsenic in human foodstuffs: A multivariate optimization methodology

A new poly(3-hydroxy butyrate)-b-poly(dimethyl amino ethyl methacrylate) amphiphilic block copolymer containing gadolinium oxide nanoparticles (PHB-PDMAEMA-Gd2O3-NPs) were synthesized and used as composite adsorbent for extraction of total arsenic. Characterization of the composite adsorbent material PHB-PDMAEMA-Gd2O3-NP was studied using spectroscopic techniques. Plackett-Burman design and central composite design were employed to screening and optimization of the experimental parameters. This composite adsorbent was utilized in ultrasound assisted-dispersive solid phase microextraction (UA-dSPµE) for the determination of total inorganic arsenic in foodstuffs through hydride generation atomic absorption spectrometry (HG-AAS). It demonstrates a linear relationship across arsenic concentration range of 0.07–1.12 µg/L with a correlation coefficient (0.996). It’s showed an enrichment factor of 128 and a limit of detection 0.02 µg/L for total inorganic arsenic determination. Accuracy of the developed method was confirmed through the analysis of certified reference materials with 96.0–98.5% recovery. It proved to be significantly useful UA-dSPµE method for determining total inorganic arsenic in different foodstuffs.

Synthesis and Optimization of Next-Generation Low-Molecular-Weight Pentablock Copolymer Nanoadjuvants.

Polymeric nanomaterials such as Pluronic®-based pentablock copolymers offer important advantages over traditional vaccine adjuvants and have been increasingly investigated in an effort to develop more efficacious vaccines. Previous work with Pluronic® F127-based pentablock copolymers, functionalized with poly(diethyl aminoethyl methacrylate) (PDEAEM) blocks, demonstrated adjuvant capabilities through the antigen presentation and crosslinking of B cell receptors. In this work, we describe the synthesis and optimization of a new family of low-molecular-weight Pluronic®-based pentablock copolymer nanoadjuvants with high biocompatibility and improved adjuvanticity at low doses. We synthesized low-molecular-weight Pluronic® P123-based pentablock copolymers with PDEAEM blocks and investigated the relationship between polymer concentration, micellar size, and zeta potential, and measured the release kinetics of a model antigen, ovalbumin, from these nanomaterials. The Pluronic® P123-based pentablock copolymer nanoadjuvants showed higher biocompatibility than the first-generation Pluronic® F127-based pentablock copolymer nanoadjuvants. We assessed the adjuvant capabilities of the ovalbumin-containing Pluronic® P123-based pentablock copolymer-based nanovaccines in mice, and showed that animals immunized with these nanovaccines elicited high antibody titers, even when used at significantly reduced doses compared to Pluronic® F127-based pentablock copolymers. Collectively, these studies demonstrate the synthesis, self-assembly, biocompatibility, and adjuvant properties of a new family of low-molecular-weight Pluronic® P123-based pentablock copolymer nanomaterials, with the added benefits of more efficient renal clearance, high biocompatibility, and enhanced adjuvanticity at low polymer concentrations.

Synthesis and characterization of stimuli responsive micelles from chitosan, starch, and alginate based on graft copolymers with polylactide-poly(methacrylic acid) and polylactide- poly[2(dimethyl amino)ethyl methacrylate] side chains

The primary objective of this paper is to serve as a comprehensive study on the synthesis of stimulus-sensitive micelles based on polysaccharides. In pursuit of this goal, functionalization with polylactide (PLA) was used as the water-resistance part and poly[2(Dimethyl amino)ethyl methacrylate] (PDMAEMA) or poly(methacrylic acid) (PMA) were employed as the stimulus-sensitive part to create micelles with a simple structure. FTIR and 1HNMR measurements were utilized to characterize the functionalized polysaccharides. Fluorescence spectroscopy was used to determine the critical micelle concentration. The average micelles' diameter, as observed in SEM and TEM pictures, ranges from 50 to 200 nm. To gain a better understanding of the potential of theses micelles for delivering drugs in a stimulus-sensitive manner, drug release tests were conducted. The cytotoxicity of these nano-vehicles was examined using the MTT assay. Utilizing MCF7 cells stained with DAPI and Mito Tracker, cellular uptake studies were also investigated. The results indicate that the behavior of the micelles is nearly same even though they used polysaccharides with various charge densities or different stimulus sensitive polymers. This approach, therefore, demonstrates that a broad range of micelle production is possible by employing diverse polysaccharides functionalized with PLA and polymethacrylates.

Self-Immolative Polymer Nanoparticles with Precise and Controllable pH-Dependent Degradation.

Polymer nanoparticles have generated significant interest as delivery systems for therapeutic cargo. Self-immolative polymers (SIPs) are an interesting category of materials for delivery applications, as the characteristic property of end-to-end depolymerization allows for the disintegration of the delivery system, facilitating a more effective release of the cargo and clearance from the body after use. In this work, nanoparticles based on a pH-responsive polymer poly(ethylene glycol)-b-(2-diisopropyl)amino ethyl methacrylate) and a self-immolative polymer poly[N,N-(diisopropylamino)ethyl glyoxylamide-r-N,N-(dibutylamino)ethyl glyoxylamide] (P(DPAEGAm-r-DBAEGAm)) were developed. Four particles were synthesized based on P(DPAEGAm-r-DBAEGAm) polymers with varied diisopropylamino to dibutylamino ratios of 4:1, 2:1, 2:3, and 0:1, termed 4:1, 2:1, 2:3, and 0:1 PGAm particles. The pH of particle disassembly was tuned from pH 7.0 to pH 5.0 by adjusting the ratio of diisopropylamino to dibutylamino substituents on the pendant tertiary amine. The P(DPAEGAm-r-DBAEGAm) polymers were observed to depolymerize (60-80%) below the particle disassembly pH after ∼2 h, compared to <10% at pH 7.4 and maintained reasonable stability at pH 7.4 (20-50% depolymerization) after 1 week. While all particles exhibited the ability to load a peptide cargo, only the 4:1 PGAm particles had higher endosomal escape efficiency (∼4%) compared to the 2:3 or 0:1 PGAm particles (<1%). The 4:1 PGAm particle is a promising candidate for further optimization as an intracellular drug delivery system with rapid and precisely controlled degradation.