Copolymer Poly Ethylene Glycol Research Articles

Synthetic genomic nanomedicine with triple-responsiveness for systemic anti-tumor therapy

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core–shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.

Influence of PEG-PPG-PEG Block Copolymer Concentration and Coagulation Bath Temperature on the Structure Formation of Polyphenylsulfone Membranes.

The effect of amphiphilic block copolymer polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG concentration in the polyphenylsulfone (PPSU) casting solution and coagulation bath temperature (CBT) on the structure, separation, and antifouling performance of PPSU ultrafiltration membranes was studied for the first time. According to the phase diagram obtained, PPSU/PEG-PPG-PEG/N-methyl-2-pyrrolidone (NMP) systems are characterized by a narrow miscibility gap. It was found that 20 wt.% PPSU solutions in NMP with the addition of 5-15 wt.% of PEG-PPG-PEG block copolymer feature upper critical solution temperature, gel point, and lower critical solution temperature. Membrane composition and structure were studied by Fourier-transform infrared spectroscopy, scanning electron and atomic force microscopies, and water contact angle measurements. The addition of PEG-PPG-PPG to the PPSU casting solution was found to increase the hydrophilicity of the membrane surface (water contact angle decreased from 78° for the reference PPSU membrane down to 50° for 20 wt.%PPSU/15 wt.% PEG-PPG-PEG membrane). It was revealed that the pure water flux increased with the rise of CBT from 18-20 L·m-2·h-1 for the reference PPSU membrane up to 38-140 L·m-2·h-1 for 20 wt.% PPSU/10-15 wt.% PEG-PPG-PEG membranes. However, the opposite trend was observed for 20 wt.% PPSU/5-7 wt.% PEG-PPG-PEG membranes: pure water flux decreased with an increase in CBT. This is due to the differences in the mechanism of phase separation (non-solvent-induced phase separation (NIPS) or a combination of NIPS and temperature-induced phase separation (TIPS)). It was shown that 20 wt.% PPSU/10 wt.% PEG-PPG-PEG membranes were characterized by significantly higher antifouling performance (FRR-81-89%, DRr-26-32%, DRir-10-20%, DT-33-45%) during the ultrafiltration of bovine serum albumin solutions compared to the reference PPSU membrane prepared at different CBTs (FRR-29-38%, DRr-6-14%, DRir-74-89%, DT-88-94%).

Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug. The selection of the nanoformulation was based on synthesis of various chitosan PEG copolymers via formaldehyde-mediated engraftment of PEG onto chitosan to form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties of the copolymer was based on the formaldehyde ratio towards nanoparticles (CP 1-4 NPs). Following the recruitment of PEG onto the chitosan polymer surface, we explored how this process influenced the stiffness of the nanoparticle using atomic force microscopy (AFM), a factor crucial for in vitro and in vivo studies. Our objective was to ensure the full functionality and inherent properties of chitosan as the parent polymer was maintained without allowing PEG to overshadow chitosan's unique cationic properties while improving solubility in neutral pH. Hence, CP 2 NP was chosen. To demonstrate the efficacy of CP 2 NP as a good delivery carrier for auranofin, we administered a dose of 3 mg/kg of auranofin, in contrast to free auranofin, which was given at 5 mg/kg. In vivo studies revealed the potency of encapsulated auranofin against TNBC cells with a severe necrotic effect following treatment superior to that of free auranofin. In conclusion, chitosan-g-PEG nanoparticles have the potential to be an excellent delivery system for auranofin, increasing its effectiveness and potentially reducing its clinical limitations.

Enhancement on electro-response of gelatin hydrogels with grafted polar groups

ABSTRACT In this article, three grafted copolymers, namely gelatin-graft-polypyrrole copolymer (gelatin-g-PPy), gelatin-graft-polyaniline copolymer (gelatin-g-PANI), and gelatin-graft-monomethyl polyethylene glycol copolymer (gelatin-g-MPEG), were successfully synthesized by the introduction of polar groups onto the gelatin matrix. Their chemical compositions were primarily characterized through Fourier Transform Infrared spectroscopy (FT-IR) and Ultraviolet-Visible spectrum (UV-Vis) analyses. The grafted gelatin hydrogels were prepared by utilizing the three grafted gelatin copolymers under an applied electric field ranging from 0 ~ 0.8 kV/mm. The impact of the electric field on the hydrogels was assessed through scanning electron microscopy (SEM), thermogravimetric analysis (TGA), dielectric analysis (DA), and dynamic mechanical analysis (DMA). SEM analysis revealed that the grafted gelatin hydrogels exhibited an ordered microstructure and larger pores when subjected to an electric field. DA testing indicated that all grafted gelatin hydrogels displayed a higher dielectric constant compared to pure gelatin, suggesting an enhanced orientation polarization of the copolymers in response to the electric field. DMA experiments confirmed that, in comparison to pure gelatin hydrogel, all the grafted gelatin hydrogels demonstrated an increased storage modulus in the direction of the applied electric field. The storage modulus increment (ΔG′) and incremental ratio (ΔG′/G′0) of the grafted gelatin hydrogels reached their maximum values at specific grafting levels. These findings suggest that the grafted gelatin hydrogels have excellent electro-responsive property.

Crystallization-driven formation poly (l-lactic acid)/poly (d-lactic acid)-polyethylene glycol-poly (l-lactic acid) small-sized microsphere structures by solvent-induced self-assembly

Improving hydrophobicity through the regulation of surface microstructures has attracted significant interest in various applications. This research successfully prepared a surface with microsphere structures using the Non-solvent induced phase separation method (NIPS). Poly(D-Lactic acid)-block-poly(ethylene glycol)-block-poly(D-Lactic acid) (PDLA-PEG-PDLA) block polymers were synthesized by ring-opening polymerization of D-Lactic acid (D-LA) using polyethylene glycol (PEG) as initiator. PLLA/PDLA-PEG-PDLA membrane with microscale microsphere morphology was fabricated using a nonsolvent-induced self-assembly method by blending the triblock copolymer with a poly(L-lactic acid) (PLLA) solution. In phase separation processes, the amphiphilic block copolymers self-assemble into micellar structures to minimize the Gibbs free energy, and the hydrophilic segments (PEG) aggregate to form the core of the micelles, while the hydrophobic segments (PDLA) are exposed on the outer corona resulting in a core-shell structure. The Stereocomplex Crystalline (SC), formed by the hydrogen bonding between PLLA and PDLA, can facilitate the transition from liquid-liquid phase separation to solid-liquid phase separation, and the PEG chain segments can enhance the formation of SC. The membrane, prepared by adjusting the copolymer content and PEG chain length, exhibited adjustable microsphere quantity, diameter, and surface roughness, enabling excellent hydrophobicity and controlled release of oil-soluble substances.

A Bioartificial Pancreas with "Immune Stealth" and Continuous Oxygen Supply for Islet Transplantation.

Transplantation of microencapsulated islet cells remains a promising strategy for the normalization of glucose metabolism control in type 1 diabetes mellitus. However, vigorous host immunologic rejection, fibrotic overgrowth around the microcapsules, and poor oxygen supply often lead to graft failure. Herein, a bioartificial pancreas is constructed, which incorporates the "stealth effect" based on polyethylene glycol copolymers and the high oxygen-carrying performance of fluorinated nanoparticles. Polycationic poly(l-lysine)-grafted-poly(ethylene glycol) is successfully coated on the surface of alginate microcapsules through electrostatic interaction, which can not only resist fibrinogen adhesion and avoid excessive fibrosis around the microcapsules but also isolate the host immune system from attacking, achieving a "stealth effect" of microencapsulated islet cells. Furthermore, the coloading of fluoride-based O2 nanocarriers gives them enhanced oxygen-carrying and continuous oxygen supply capabilities, thereby effectively prolonging the survival of islet cells. The intracapsular islet cells still display similar cell viability and almost normal insulin secretion function even in long-term culture under hypoxic conditions. Collectively, here a new approach is opened for microencapsulated islets to efficiently evade host immune attack and improve oxygen supply and a promising strategy is provided for islet transplantation in type 1 diabetes mellitus.

Improved copper-based catalysts for alcohol-assisted CO2 hydrogenation: A comparative study between novel nano-stabilized and deposition-precipitation method

A growing awareness of the need to control CO2 concentration in atmosphere spurs the demand for novel technologies to convert CO2 to useful chemicals. The conversion of CO2 into high-quality liquid fuel such as methanol is a primary focus, and using active catalysts is the key to achieving successful methanol synthesis from CO2 hydrogenation under mild conditions. A new way of synthesizing catalysts with highly dispersed nano copper particles, as well as the characteristics of the catalysts are reported in this study. This is the first instance of methanol catalysts being prepared using a combination of copolymer of polyethylene glycol and maleic acid (PEG-MA) as a stabilizer and layered hydrotalcite (HTC) as a support material. This resulted in a significant decrease in particle size and exhibited efficient catalytic performance in a 1-butanol promoted CO2 hydrogenation reaction at 170 °C, 3 MPa. The work also confirms the status of Zn as an influential factor for methanol synthesis. The application of ion-exchange process and stabilizers in catalyst preparation process effectively improves the CO2 conversion rate and methanol selectivity, which also inspires the development of catalysts in various fields.

Unique Dye-Sensitized Solar Cell Using Carbon Nanotube Composite Papers with Gel Electrolyte

We propose a unique form of dye-sensitized solar cells (DSSCs), paper DSSCs based on carbon-nanotube (CNT) composite papers, and the use of a gel electrolyte for the paper DSSC. In our previous study, we succeeded in developing the paper DSSC. However, its performance and lifetime were not sufficient. We considered that the problem was the use of liquid-type electrolyte. To improve the performance of the paper DSSC, a gel electrolyte was introduced to increase safety and durability. Here, a polymer gel electrolyte was synthesized using a copolymer of polyethylene glycol (PEG) and polyvinylidene fluoride (PVDF) as a matrix, mixed with iodine and potassium iodide. The resulting paper DSSC had a fill factor (FF, a performance indicator) of 0.248 and a conversion efficiency of 2.43 × 10−5% with an extended working time (lifetime) of more than 110 min. Further modifications were made to the metallic CNT composite paper and the gel electrolyte, resulting in an increased conversion efficiency of 2.02 × 10−3%. This study suggests the potential of gel electrolytes in enhancing the performance of paper DSSCs, providing new insights for their future applications.

Preparation, characterization, and properties of lutein block polyethylene glycol copolymer loading with lutein nanoparticles

Preparation, characterization, and properties of lutein block polyethylene glycol copolymer loading with lutein nanoparticles

Vinyl Sulfone-functionalized Acetalated Dextran Microparticles as a Subunit Broadly Acting Influenza Vaccine.

Influenza is a global health concern with millions of infections occurring yearly. Seasonal flu vaccines are one way to combat this virus; however, they are poorly protective against influenza as the virus is constantly mutating, particularly at the immunodominant hemagglutinin (HA) head group. A more broadly acting approach involves Computationally Optimized Broadly Reactive Antigen (COBRA). COBRA HA generates a broad immune response that is capable of protecting against mutating strains. Unfortunately, protein-based vaccines are often weekly immunogenic, so to help boost the immune response, we employed the use of acetalated dextran (Ace-DEX) microparticles (MPs) two ways: one to conjugate COBRA HA to the surface and a second to encapsulate cGAMP. To conjugate the COBRA HA to the surface of the Ace-DEX MPs, a poly(L-lactide)-polyethylene glycol co-polymer with a vinyl sulfone terminal group (PLLA-PEG-VS) was used. MPs encapsulating the STING agonist cGAMP were co-delivered with the antigen to form a broadly active influenza vaccine. This vaccine approach was evaluated in vivo with a prime-boost-boost vaccination schedule and illustrated generation of a humoral and cellular response that could protect against a lethal challenge of A/California/07/2009 in BALB/c mice.

Interleukin-10 plasmid delivery by polymeric nanocarrier shows efficient and safe tissue repair in acute muscle damage models in mice

We established a custom-designed nanocarrier for in vivo delivery of an immunomodulatory plasmid capable of facilitating tissue repair in acute muscle damage models in mice. The nanocarrier was constructed by selecting from versatile cationic designs that were used to complex with a negatively charged plasmid, while the excessive positive charge was shielded by the poly (glutamic acid)-polyethylene glycol co-polymer. The best-performing formulation was identified by high throughput screening in macrophages, in which we obtained the hierarchical ranking in terms of reporter gene expression (GFP plasmid, pGFP) and macrophage polarization status (interleukin 10 plasmid, pIL-10). For proof-of-principle, we performed intramuscular (IM) injection of pGFP nanocarrier in a cardiotoxin-induced muscle injury model. After confirming the in vivo GFP transfection, we demonstrated protected delivery of pIL-10 to the injured muscle site, leading to an accelerated tissue repair outcome. Immunophenotyping analysis revealed the increased number of M2 macrophages and regulatory T cells, as well as increased IL-10 production at muscle site. The effectiveness of the pIL-10 carrier was interfered by pharmaceutical macrophage depletion using pre-injected clodronate liposome. When intravenously (IV) injected, our pIL-10 nanocarrier preferentially biodistributed in the injured muscle (owing to transiently decreased blood vessel integrity) and improved tissue repair. Unlike IL-10 protein (that was clinically abandoned), sustained IL-10 production by our nanocarrier dramatically reduced the degree of spleen enlargement and kidney inflammation, suggesting a favorable safety characteristic in vivo.

Exploring structure and dynamics of the polylactic‐co‐glycolic acid–polyethylene glycol copolymer and its homopolymer constituents in various solvents using all‐atom molecular dynamics

AbstractPolylactic‐co‐glycolic acid (PLGA)‐basedpolymers are synthetic materials that are prominent in drug delivery. PLGA homopolymer is biodegradable, biocompatible and is often polymerized to polyethylene glycol (PEG) to form a block copolymer used to form core‐shell nanoparticles. PEG is known for reducing blood clearance and opsonization, in addition to imparting “stealth” properties to various drugs and biomaterials. Current formulation methodologies for PLGA–PEG copolymer nanoparticles can be tuned to control key parameters for improved therapeutic delivery; however, molecular‐level understanding of copolymer‐solvent interactions during nanoparticle formulation is lacking. Therefore, three different PLGA–PEG/solvent pairs are examined, in comparison to their homopolymer constituents, to better understand copolymerization effects and its impact on nanoparticle formulation. Results show that at room temperature PLGA–PEG oligomers in dimethyl sulfoxide are the most rigid in good solvent conditions (Flory exponent >0.5) and have the largest end‐to‐end relaxation times when compared to acetone and water. PEG has a Flory exponent of ~0.5 in both water and acetone, showing that the molecular dynamic model that is employed can reproduce its amphiphilic nature in solution. Knowledge of PLGA–PEG structure and dynamics can be used in the design of novel biomedical technologies that improve drug efficacy and reduce cost of treatment.

Optimization of Melt-mixing Transesterifi cation of Polylactide by Polyethylene Glycol Employing Response Surface Methodology

A process for preparing polylactide-block-polyethylene glycol (PLA-b-PEG) copolymers has been developed and optimized by employing a transesterifi cation reaction in a melt-mixing process. The reaction was carried out in a counter-rotating mixer unit, using polyethylene glycol (PEG) and tetrabutyl titanate (TBT) catalyst. The effects of PEG weight percentage, catalyst contents, temperatures, and rotor speeds on chemical structures of the resulting PLA-b-PEG were examined, in terms of number average molecular weight (Mn), weight average molecular weight (Mw), in-chain PEG contents (wt.% PEG), and specifi c mechanical energy (SME) imparted by the mixer. The process parameters were optimized using a central composite rotatable design (CCRD) response surface methodology (RSM). The CCRD was designed with four variables at three levels of variations (-1, 0, -1), four replicates center point, and a redundancy factor (α) of 2.000. The responses (Mn, Mw, wt.% PEG, and SME) from 28 experimental trials were analyzed by a multiple linear regression fi tting, a second-order equation, and the RSM model. Mn and Mw of the products were determined by gel permeation chromatography (GPC). The in-chain PEG content was examined by nuclear magnetic resonance (1H-NMR) spectroscopy. The results show that the PEG weight percentage and the reaction temperature signifi cantly affect (P< 0.05) Mw and Mn of the products, which are drastically decreased with an increase in the PEG weight percentage and temperature. A quadratic interaction is observed between the PEG weight percentage and temperature, indicating that high reaction temperature leads to lower PEG conversions, due to undesirable competing thermal-oxidative degradations of PEG in the presence of the catalyst. Optimum operating conditions on the PEG weight percentage, catalyst contents, temperatures, and rotor speed for obtaining high Mw with high wt.% PEG was identifi ed. Although the optimal conditions are observed at the boundary level, the model serves as a platform for effective preparation of PLA-b- PEG copolymers with designed molecular weight and chemical structures. Further optimization of the model may be conducted by extending the range of independent factor levels. The resulting fl exible PLA-b-PEG copolymers, with tunable structures and properties, have high potential for use as singlecomponent degradable bioplastics with excellent mechanical properties, plasticizers, or toughening agent for enhancing PLA’s toughness.

Emerging uses of PLA-PEG copolymer in cancer drug delivery.

Traditional therapies need high systematic dosages that not only destroys cancerous cells but also healthy cells. To overcome this problem recent advancement in nanotechnology specifically in nanomaterials has been extensively done for various biological applications, such as targeted drug delivery. Nanotechnology, as a frontier science, has the potential to break down all the obstacles to be more effective and secure drug delivery system. It is possible to develop nanopolymer based drug carrier that can target drugs with extreme accuracy. Polymers can advance drug delivery technologies by allowing controlled release of therapeutic drugs in stable amounts over long duration of time. For controlled drug delivery, biodegradable synthetic polymers have various benefits over non-biodegradable polymers. Biodegradable polymer either are less toxic or non-toxic. Polylactic Acid (PLA) is one of the most remarkable amphipathic polymers which make it one of the most suitable materials for polymeric micelles. Amphiphilic nanomaterial, such as Polyethylene Glycol (PEG), is one of the most promising carrier for tumor targeting. PLA-PEG as a copolymer has been generally utilized as drug delivery system for the various types of cancer. Chemotherapeutic drugs are stacked into PLA-PEG copolymer and as a result their duration time delays, hence medications arrive at specific tumor site.

In silico modeling of emodin’s interactions with serine/threonine kinases and chitosan derivatives

Natural products are quickly gaining relevance as effective anticancer agents, and one example, emodin, possesses inhibitory activity against a broad spectrum of kinases, regulatory enzymes that control biological activity via phosphorylation of other molecules. Herein, through protein-ligand docking, we investigated the effect of the interaction of emodin with serine/threonine kinases, a subclass of kinases that is overexpressed in many cancers, which is implicated in phosphorylation cascades. These cascades act as intracellular messaging systems, and in the case of cancer, modify protein expression in the cell to essentially make it immortal. Thus, competitive inhibition by emodin can reduce the expression of a wide range of proteins required for essential cell function, resulting in cell death. Because the majority of serine/threonine kinases have similar active sites, we have successfully created a blueprint for emodin binding and interactions with active site residues, which include many hydrophobic interactions and minimal amounts of hydrogen bonding. Through molecular dynamics we found that emodin forms favorable interactions with chitosan and chitosan PEG (polyethylene glycol) copolymers, which could aid in loading drugs into nanoparticles (NPs) for targeted delivery to cancerous tissue. Both polymers demonstrated reasonable entrapment efficiencies, which encourages experimental exploration of emodin through targeted drug delivery vehicles and their anticancer activity.

Synthesis, physical and mechanical properties of amphiphilic hydrogels based on polycaprolactone and polyethylene glycol for bioapplications: A review

During the past decades, amphiphilic hydrogels found versatile applications in biomaterial field due to their suitable mechanical properties and control on releasement of hydrophobic substrates. Polyethylene glycol (PEG) and polycaprolactone (PCL) are FDA approved polymers that were used together in lots of research articles due to their complementary properties. This review focused on synthetic methods, physical, and mechanical properties as well as sol–gel-sol phase transition behavior of amphiphilic hydrogels based on polyethylene glycol (PEG) and polycaprolactone (PCL). Physical hydrogels were formed base on the hydrophobic interaction between copolymers of PCL and PEG or based on supramolecular chemistry. Also, chemical hydrogels synthesized via free radical crosslinking and chemical coupling reaction between functionalized prepolymers. Both types of physical and chemical hydrogels are biocompatible and biodegradable. Physical hydrogels are thermo-sensitive and were used as injectable hydrogels that can be sensitive to pH or other triggers. In addition, chemical hydrogels could be used as tissue scaffolds according to their mechanical properties.

Preparation of QDs@SiO2-PEG-LMPET and its influence on crystallization and luminescence of polyethylene terephthalate

The composite particles composed of quantum dots coated with silica and grafted with copolymer of polyethylene glycol and low molecular weight polyethylene terephthalate (QDs@SiO2-PEG-LMPET) are synthesized. The internal QDs provide luminescent performance and combine with SiO2 to form QDs@SiO2 with good dispersion to solve the defect that small-sized SiO2 is prone to agglomerate. The block polymer LMPET-PEG grafted on the surface can make the composite particles better compatible with the PET matrix. In summary, QDs@SiO2-PEG-LMPET not only play the same role as SiO2 to enhance the crystallization performance of PET matrix, but also provide stable luminescence performance, which is multifunctional additive with broad application prospects.

The effect of topology of PEG chain on the stability of micelles in brine and serum

Polymeric micelles are promising vehicles for drug delivery these years. The stability of micelles in blood system is very important for the encapsulated therapeutic agents reaching the targeting area. However, generally, micelles are not stable in the presence of proteins and ions after being injected intravenously. The topology of polymer chain on the surface of micelles plays a key role on the stability of micelles. Here we have prepared flower micelles and the traditional micelles via self-assembly of triblock and diblock copolymer of polyethylene glycol (PEG) and poly(ε-caprolactone) (PCL) in water. The special PEG shell of flower micelles prevents micelles from ions and proteins, which endows the micelles with the ability to resist aggregation. The experiment results show that flower micelles are much more stable in the presence of serum and salt than traditional micelles, which indicates these micelles would be promising in drug delivery in the future.

Mannosylated Cationic Copolymers for Gene Delivery to Macrophages.

Macrophages are desirable targets for gene therapy of cancer and other diseases. Cationic diblock copolymers of polyethylene glycol (PEG) and poly-L-lysine (PLL) or poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (pAsp(DET)) are synthesized and used to form polyplexes with a plasmid DNA (pDNA) that are decorated with mannose moieties, serving as the targeting ligands for the C type lectin receptors displayed at the surface of macrophages. The PEG-b-PLL copolymers are known for its cytotoxicity, so PEG-b-PLL-based polyplexes are cross-linked using reducible reagent dithiobis(succinimidyl propionate) (DSP). The cross-linked polyplexes display low toxicity to both mouse embryonic fibroblasts NIH/3T3 cell line and mouse bone marrow-derived macrophages (BMMΦ). In macrophages mannose-decorated polyplexes demonstrate an ≈8 times higher transfection efficiency. The cross-linking of the polyplexes decrease the toxicity, but the transfection enhancement is moderate. The PEG-b-pAsp(DET) copolymers display low toxicity with respect to the IC-21 murine macrophage cell line and are used for the production of non-cross-linked pDNA-contained polyplexes. The obtained mannose modified polyplexes exhibit ca. 500-times greater transfection activity in IC-21 macrophages compared to the mannose-free polyplexes. This result greatly exceeds the targeting gene transfer effects previously described using mannose receptor targeted non-viral gene delivery systems. These results suggest that Man-PEG-b-pAsp(DET)/pDNA polyplex is a potential vector for immune cells-based gene therapy.

Paclitaxel-loaded polymeric nanoparticles based on α-tocopheryl succinate for the treatment of head and neck squamous cell carcinoma: in vivo murine model

: The prognosis of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC) is generally poor. New treatments are required to supplement the current standard of care. Paclitaxel (PTX), an effective chemotherapeutic for HNSCC, has serious side effects. A polymeric nanocarrier system was developed for the delivery of PTX to improve HNSCC treatment. This study aimed to evaluate the antitumor efficacy of PTX-loaded polymeric nanoparticles based on α-TOS (PTX-NPs) administered by direct intratumoral injection into a Hypopharynx carcinoma squamous cells (FaDu) tumor xenograft mouse model. The nanocarrier system based on block copolymers of polyethylene glycol (PEG) and a methacrylic derivative of α-TOS was synthesized and PTX was loaded into the delivery system. Tumor volume was measured to evaluate the antitumor effect of the PTX-NPs. The relative mechanisms of apoptosis, cell proliferation, growth, angiogenesis, and oxidative and nitrosative stress were detected by Western blotting, fluorescent probes, and immunohistochemical analysis. The antitumor activity results showed that compared to free PTX, PTX-NPs exhibited much higher antitumor efficacy and apoptosis-inducing in a FaDu mouse xenograft model and demonstrated an improved safety profile. Ki-67, EGFR, and angiogenesis markers (Factor VIII, CD31, and CD34) expression were significantly lower in the PTX-NPs group compared with other groups (p < .05). Also, PTX-NPs induced oxidative and nitrosative stress in tumor tissue. Direct administration of PTX-loaded polymeric nanoparticles based on α-Tocopheryl Succinate at the tumor sites, proved to be promising for HNSCC therapy.