Nanogel Dispersions Research Articles

Subcutaneous angiogenesis induced by transdermal delivery of gel-in-oil nanogel dispersion

Subcutaneous transplantation aims to enhance the growth and functionality of transplanted cells for therapeutic outcomes in tissue engineering. However, the limited subcutaneous vascular network poses a challenge. Conventional methods involve co-transplantation with endothelial cells or angiogenic scaffold implantation, but they have drawbacks like tissue inflammation, compromised endothelial cell functionality, and the risk of repeated scaffold transplantation. Effective techniques are needed to overcome these challenges. This study explores the potential of G/O-NGD, a gel-in-oil nanogel dispersion, as a transdermal carrier of proliferative factors to promote angiogenesis in subcutaneous graft beds before cell transplantation. We observed robust subcutaneous angiogenesis by delivering varying amounts of bFGF using the G/O-NGD emulsion. Quantitative analysis of several parameters confirmed the efficacy of this method for building a subcutaneous vascular network. G/O-NGD is a biodegradable material that facilitates localized transdermal delivery of bFGF while maintaining its activity. The findings of this study have significant implications in both medical and industrial fields.

Fluorescent poly[N‐(2‐hydroxypropyl) methacrylamide] nanogel by dispersion polymerization as a contrast agent for live‐cell imaging

AbstractHere, we report a novel dispersion polymerization for the preparation of cross‐linked poly[N‐(2‐hydroxypropyl) methacrylamide] (PHPMA)‐based nanogels in water/2‐methoxyethanol mixture (H2O/MetCel), initiated with potassium persulfate (KPS), and stabilized with poly(vinyl alcohol) 25/140 (PVA) and sodium dodecyl sulfate (SDS). Obtained nanogels were characterized using transmission (TEM) and cryogenic transmission electron microscopy (cryo‐TEM), dynamic light scattering (DLS), asymmetric flow field‐flow fractionation (A4F), nuclear magnetic resonance spectroscopy (NMR), and Raman spectroscopy methods in terms of size, particle size distribution, morphology, and structure. N‐(2‐hydroxypropyl) methacrylamide (HPMA) was copolymerized with 20 wt% ethylene dimethacrylate (EDMA) resulting in 138 nm poly[N‐(2‐hydroxypropyl) methacrylamide‐co‐ethylene dimethacrylate] (PHPMA‐EDMA) nanogel dispersion with irregular shape and core‐shell type structure. Next, we copolymerized HPMA with 20 wt% EDMA and 10 wt% propargyl methacrylate (PMA) to incorporate reactive functionality into the final core‐shell type 120 nm poly[N‐(2‐hydroxypropyl) methacrylamide‐co‐ethylene dimethacrylate‐co‐propargyl methacrylate] (PHPMA‐EDMA‐PMA) nanogel dispersion. Then, the biocompatibility of PHPMA‐EDMA‐PMA nanogel was proved using rat mesenchymal stem cells (rMSC), and human foreskin fibroblasts (BJ). PHPMA‐EDMA‐PMA nanogel was fluorescently labeled with sulfo‐cyanine3 azide resulting in 131 nm nanogel. We performed in vitro uptake studies with fluorescently labeled PHPMA‐EDMA‐PMA nanogel using rMSC showing that the fluorescently labeled PHPMA‐EDMA‐PMA nanogel was well‐distributed in the cytosol and taken up into lysosomes.

Prevention and Repair of Ultraviolet B-Induced Skin Damage in Hairless Mice via Transdermal Delivery of Growth Factors Immobilized in a Gel-in-Oil Nanoemulsion.

Ultraviolet (UV) radiation from the sun or artificial sources is one of the primary causes of skin damage, including sunburns, tanning, erythema, and skin cancer. Among the three different types of UV rays, UVB rays have a medium wavelength that can penetrate the epidermal layer of the skin, resulting in sunburn, suntan, blistering, and melanoma in case of chronic exposure. This study aimed to evaluate the preventive and therapeutic effects of a gel-in-oil nanogel dispersion (G/O-NGD) as a transdermal delivery biomolecular carrier for skin damage caused by UVB light. The efficacy of this carrier against UVB-induced skin damage was investigated in vivo by delivering different growth factors (GFs) encapsulated in a G/O-NGD. Artificial UVB light was used to induce skin damage in nude mice, followed by the transdermal application of five GF [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor (TGF)-1, and insulin-like growth factor (IGF)-α]-immobilized G/O-NGD. Among these GFs, VEGF and bFGF promoted angiogenesis, while EGF, TGF-1, and IGF-α promoted the repair and regeneration of damaged cells. The results showed that G/O-NGD was superior to heparin-immobilized G/O-NGD in reducing UVB-induced skin damage, such as erythema, epidermal water reduction, inflammation, and dermis thickening. In addition, G/O-NGD could prevent and treat abnormal follicle proliferation caused by UVB rays and exhibited potential to repair lipid glands. Overall, our results demonstrate the potential of G/O-NGDs for the treatment of UVB-induced skin damage.

Development of alginate-spermidine micro/nanogels as potential antioxidant and anti-inflammatory tool in peripheral nerve injuries. Formulation studies and physico-chemical characterization

The development of a successful strategy to ensure a full recovery in patients affected by peripheral nerve injury (PNI), one of the most debilitating pathologies, is, still today, a major clinical challenge. Herein, spermidine (SP), an endogenous polyamine, is employed with a dual role: as cross-linking agent for alginate (ALG) and as antioxidant and anti-inflammatory compound. In particular, micro/nanogels based on the ionic interaction between ALG and SP were obtained via ionotropic gelation. Different ALG concentrations and viscosity grades and different SP concentrations were considered. The influence of such variables on micro/nanogels size was investigated by means of a Design of Experiments (DoE) approach (full factorial design). The formation of micro/nanogels was proved by Scanning Electron Microscope (SEM) analysis and by rheological and profilometry measurements. Fourier Transform Infrared (FTIR) measurements performed on nanogels of optimal composition confirmed SP-ALG interaction. The addition of trehalose as cryoprotectant agent to nanogel dispersion was considered in view of the employment of freeze-drying process to obtain a stable product.Moreover, in vitro studies on Schwann cells proved the ability of SP of expressing antioxidant and anti-inflammatory properties, even if involved in the formation of nanogels.

Solution properties of hydrophobic derivatives of poly(ethylene-alt-maleic acid)

A library of hydrophobically modified polyelectrolytes was prepared by reacting linear alkyl amines with poly(ethylene-alt-maleic anhydride), followed by hydrolysis of the residual anhydride groups. Every reacted anhydride gives a pendent alkylamide plus a carboxylic acid group, and the result is a comb architecture. The lengths of the alkyl side chains were 3, 6, 8, or 10 carbons. The density of alkyl side chains was expressed as the fraction of anhydride groups reacted with alkyl amines (25 %, 50 %, and 75 %). The dominant factor influencing the aqueous solution properties is the alkyl chain length. C3 polymers had no pyrene receptive hydrophobic domains. C6 and C8 polymers bound pyrene at pH less than 6 and do not give reliable dynamic light scattering (DLS) results. C10 polymers displayed pyrene binding across the pH range and, based on DLS and AFM data, possibly appear as unimolecular nanogel dispersions from pH 7–9. At pH values > 9, our DLS measurements gave low-quality data, whereas at pH less than 7 both DLS and AFM results indicated nanogel aggregation. The C10 polymer properties were surprisingly insensitive to the degree of hydrophobic substitution over the range of 25–75 %. The nanogels with low alkyl contents were slightly more swollen and had high NaCl critical coagulation concentrations compared to the high alkyl content nanogels. These polymers are of particular interest because the non-derivatized maleic moieties in the polymers can form ester linkages to cellulose in an aqueous, catalyst-free process.

Injectable Thermosensitive Iodine-Loaded Starch-g-poly(N-isopropylacrylamide) Hydrogel for Cancer Photothermal Therapy and Anti-Infection.

Although photothermal therapy (PTT) can effectively eliminate tumors, the normal tissues near tumors are inevitably damaged by heat and infected by bacteria, which greatly limits the therapeutic effect. In this work, an injectable thermosensitive hydrogel based on iodine-loaded starch-g-poly(N-isopropylacrylamide) (PNSI) is developed to overcome this problem. FTIR, 1 H NMR, and UV-vis spectra confirm the graft copolymerization of poly(N-isopropylacrylamide) with starch and the formation of "iodine-starch" complex. Transmission electron microscope images show PNSI polymer self-assembles into regular spherical nanogel with a size of ≈50nm. The concentrated nanogel dispersion is a sol at room temperature and transforms to hydrogel at body temperature. Under NIR laser irradiation for 10min, the ΔT of the nanogel dispersion approachs about 20°C with excellent thermal stability and high cytotoxicity due to the photothermal effect of the "iodine-starch" complex. After intratumor injection, this injectable hydrogel efficiently inhibites the tumor growth under 808nm laser irradiation. Furthermore, it can also suppress Staphylococcus aureus infection in the wound post-PTT due to the release of iodine, which promotes wound healing. Therefore, this injectable thermosensitive "iodine-starch" composite hydrogel with advantages of good biocompatible and easy preparation possesses potential application for tumor photothermal therapy and antibacterial infection.

Gentamicin nanogel films based on Carrageenan-Prosopis africana for improved wound healing

<img src=” https://s3.amazonaws.com/production.scholastica/article/35438/large/prnano_722021ga.jpg?1651243768”> Dermal injuries (e. g., trauma, surgical incisions, and burns) are burdensome health care issues in the world. The delayed healing process can be caused by aerobic and anaerobic bacteria infections, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus and Enterococcus species, Pseudomonas aeruginosa, Peptostreptococcus, and Coliforms. Therefore, reduction of bacterial burden to an acceptable level promotes healing. The rationale for this innovative wound dressing relies on good hydration as the single most important external factor responsible for optimal wound healing. Objective: To study the wound healing potential of GEN nanogel films based on natural polymers using carrageenan (CAR) and Prosopis africana (PRO), a local African plant. Method: Nanogel dispersions and films were characterized by their physical and technological properties, microenvironment, Zeta sizer, Differential Scanning Calorimetry, FTIR spectroscopy, in vitro drug release, and efficacy of wound healing in the rat in a full-thickness excisional model. Results: GEN was dispersed in the polymers, with PROGEN films appearing smoother than CARGEN. Wound closure rate was 88, 76, and 72 % with PROGEN, CARGEN, and GENTA cream, respectively, whereas drug release was sustained in the order of PROGEN (~99 % at 8 h), CARGEN (83 % at 10 h), and pure GENTA powder (81% at 1 h). Topical administration of GEN nanogel-films significantly accelerated (< 15 days) wound closure with no scabbing observed compared to the commercial GENTA cream used. Conclusion: GEN-loaded PROGEN and/or CARGEN films have the potential for developing an improved and affordable topical treatment for cutaneous wound healing.

Poly(N-isopropylacrylamide) copolymer nanogels with thermogelling ability prepared by a single step of dispersion polymerization

The copolymer nanogels composed of two N-substituted acrylamides with different water solubility, N-isopropylacrylamide (NIPAM, water-soluble) and N-t-butylacrylamide (TBAM, water-insoluble), were prepared by free-radical polymerization in the presence of sodium dodecyl sulfate (SDS) as a dispersant and found to exhibit thermogelling ability at very low concentrations. To investigate the structure of the P(NIPAM-TBAM) nanogel and its formation mechanism in dispersion polymerization, we prepared the nanogels by changing the conditioning time, which is the time between the addition of SDS to the monomer solution and the start of polymerization, and compared the thermogelling properties of the resultant nanogels. As the conditioning time increased, (i) the hydrodynamic diameter of the nanogel decreased, (ii) the sol–gel and gel-syneresis transition temperatures of the nanogel dispersion decreased, and (iii) the storage moduli of the nanogel dispersion in a gel state increased. These results indicate that the P(NIPAM-TBAM) nanogel has a block-like structure composed of the TBAM-rich brushes and the NIPAM-rich core with three-dimensional polymer network, and that the TBAM ratio in the brushes increases with an increase in the conditioning time. It should be noted that the critical gelation concentration of the P(NIPAM-TBAM) nanogel dispersion was very low (∼1.3 wt%), compared with other thermogelling polymers reported in literatures. This low gelation concentration can be attributed to the gel structure of the nanogel core because the NIPAM-rich core can retain water inside even when the TBAM-rich brushes are dehydrated and crosslink with each other to induce gelation of the system.

Gel-in-water nanodispersion for potential application in intravenous delivery of anticancer drugs

Organogels are semi-solid systems that can gel organic liquids at low concentrations. The use of organogels in drug delivery has grown rapidly in the last decade owing to their fibrous microstructure and suitability for different routes of administration. The current study is characterized by nanogel dispersion (NGD) development based on emulsion technology. The efficiency of this organogel based NGD as a carrier for anticancer drugs was assessed both invitro and invivo. 12-Hydroxystearic acid formed an organogel with lipiodol and encapsulated the anticancer drug paclitaxel. The gel-in-water (G/W) nanodispersion was prepared via ultrasonication and stabilized by a nonionic surfactant. The results showed that the organogel enabled sustained drug release from G/W nanodispersion over time, along with enhanced cellular uptake. The prepared G/W nanodispersion was found to be biocompatible with mouse hepatocytes and fibroblast cells invitro, whereas paclitaxel-loaded G/W nanodispersion showed cytotoxicity (p <0.05) against lung cancer (A549) cell lines. Similarly, intravenous administration of paclitaxel-loaded G/W nanodispersion exerts an anticancer effect against lung cancer invivo, with a significant decrease in tumor volume (p <0.05). Therefore, the proposed G/W nanodispersion could be a promising carrier for chemotherapy agents with sustained drug release and better therapeutic outcomes against cancer.

Thermo- and UV-responsive amphiphilic nanogels via reversible [4+4] photocycloaddition of PEG/PCL-based polyurethane dispersions

Amphiphilic nanogels are emerging as promising materials for several applications due to their high loading capacity of hydrophobic substances. In this context, a thermoresponsive anthracene end-capped hyperbranched polyurethane (HPU-AM) based on poly(ethylene glycol), polycaprolactone-triol, and isophorone diisocyanate, was used as a platform for nanogel preparation. Both polymer synthesis and functionalization with anthracene were one-pot and controlled. HPU-AM self-assembled in aqueous solutions to form micelles, while heating above the solution cloud point (Tcp) led to phase separation and globule formation, as verified by 1H nuclear magnetic resonance and dynamic light scattering experiments. Nanogel dispersions were prepared by UV-irradiation of the globule dispersions. The UV-light (λ = 365 nm) triggers the [4+4] cycloaddition of the anthracene chain-ends, yielding chemically cross-linked nanogels. Their hydrodynamic radius was tuned from 28 to 50 nm by varying the quench temperature (T > Tcp) and HPU-AM concentration. Evidence of nanogel softness, spherical morphology, narrow size distributions, and phase-segregated inner structure was provided by microscopy, light scattering, and Nile-red loading experiments. The hydrodynamic volume of the nanogels was reversibly reduced up to 85% by heating from 15 to 45 °C. Finally, irradiation of the nanogel dispersions at λ = 280 nm cleaved the anthracene dimer, partially reverting the crosslinking, and promoting nanogel disaggregation into micelles of hydrodynamic radius of 7 nm.

Injectable Adhesive Hydrogel as Photothermal‐Derived Antigen Reservoir for Enhanced Anti‐Tumor Immunity

AbstractLow vaccine immunogenicity and tumor heterogenicity greatly limit the therapeutic effect of tumor vaccine. In this study, a novel injectable adhesive hydrogel, based on thermosensitive nanogels containing catechol groups and loaded with in situ‐forming MnO2 nanoparticles, is constructed to overcome these issues. The concentrated nanogel dispersion transforms into an adhesive hydrogel in situ after intratumoral injection. The photothermal effect of the loaded MnO2 nanoparticles induces immunogenic cell death to release mass autologous tumor‐derived protein antigens under near‐infrared irradiation, which act as ideal immune stimulating substances avoiding the problem of tumor heterogenicity and are captured by the in situ‐forming adhesive hydrogel. The antigens‐captured adhesive hydrogel acts as an “antigen reservoir” and releases these captured antigens to recruit more dendritic cells to stimulate an intensive and lasting anti‐tumor immune response mediated by CD8+ T cells. The primary tumors can be almost completely disappeared within 4 days without relapse, and the growth of the distal tumors and rechallenged tumors are also effectively inhibited by the treatment with the injectable adhesive hydrogel‐based photothermal therapy. Therefore, the proposed “antigen reservoir” strategy shows the great potential application as an in situ‐forming personalized vaccine to enhancing the cancer immune therapy.

Understanding the Phase and Morphological Behavior of Dispersions of Synergistic Dual-Stimuli-Responsive Poly(N-isopropylacrylamide) Nanogels.

This work represents a detailed investigation into the phase and morphological behavior of synergistic dual-stimuli-responsive poly(N-isopropylacrylamide) nanogels, a material that is of considerable interest as a matrix for in situ forming implants. Nanogels were synthesized with four different diameters (65, 160, 310, and 450 nm) as monodispersed particles. These different samples were then prepared and characterized as both dilute (0.1 wt %) and concentrated dispersions (2–22 wt %). In the dilute form, all of the nanogels had the same response to the triggers of the physiological temperature and ionic strength. In water, the nanogels would deswell when heated above 32 °C, while they would aggregate if heated above this temperature at the physiological ionic strength. In the concentrated form, the nanogels exhibited a wide range of morphological changes, with liquid, swollen gel, shrunken gel, and aggregate structures all possible. The occurrence of these structures was dependent on many factors such as the temperature, ionic strength of the solvent, size and ζ-potential of the nanogel, and dispersion concentration. We explored these factors in detail with techniques such as visual studies, rheology, effective volume fraction, and shape factor measurement. The different-sized nanogels displayed differing phase and morphological behavior, but generally higher concentrations of the nanogels (>7 wt %) yielded gels in water with the transitions depending on the temperature. The smallest nanogel (65 nm diameter) exhibited the most unique behavior; it did not form a swollen gel at any concentration tested. Shape factor measurement for the nanogel samples showed that two of the larger three samples (160 and 310 nm) had core–shell structures with denser core cross-linking, while the smallest nanogel sample displayed a homogeneous cross-linked structure. We hypothesize that the smallest nanogels are able to undergo more extensive interpenetration compared to the larger nanogels, which meant that the smallest nanogel was not able to form a swollen gel. In the presence of salt at 12 wt %, all of the nanogels formed aggregates when heated above 35 °C due to the screening of the electrostatic stabilization by the salt. This work revealed unique behavior of the smallest nanogel with a homogeneous cross-linked structure; its phase and morphological behavior were unlike a particle dispersion, rather these were more similar to those of a branched polymer solution. In total, these findings can be used to provide information about the design of poly(N-isopropylacrylamide) nanogel dispersions for different applications where highly specific spatiotemporal control of morphology is required, for example, in the formation of in situ forming implants or for pore blocking behavior.

Nanogel-Based Filler-Matrix Interphase for Polymerization Stress Reduction

A novel filler-resin matrix interphase structure was developed and evaluated for dental composite restoratives. Nanogel additives were chemically attached to the filler surface to use this created interphase as a potential source of compliance to minimize stress development during polymerization. In addition, we evaluated the effects of free nanogel dispersion into the resin matrix, combined or not with nanogel-modified fillers. Nanogels with varied characteristics were synthesized (i.e., size, 5 and 11 nm; glass transition temperature, 28 °C to 65 °C). Glass fillers were treated with trimethoxyvinylsilane and further reacted with thiol-functionalized nanogels via a free radical thiol-ene reaction. γ-Methacryloxypropyltrimethoxysilane-surface treated fillers were used as a control. Composites were formulated with BisGMA/TEGDMA resin blend with 60 wt% fillers with nanogel-modified fillers and/or free nanogel additives at 15 wt% in the resin phase. Polymerization kinetics, polymerization stress, volumetric shrinkage, and rheological and mechanical properties were evaluated to provide comprehensive characterization. Nanogel-modified fillers significantly reduced the polymerization stress from 2.2 MPa to 1.7 to 1.4 MPa, resulting in 20% stress reduction. A significantly greater nanogel content was required to generate the same magnitude stress reduction when the nanogels were dispersed only in the resin phase. When the nanogel-modified filler surface treatment and resin-dispersed nanogel strategies were combined, there was a stress reduction of 50% (values of 1.2 to 1.1 MPa). Polymerization rate and volumetric shrinkage were significantly reduced for systems with nanogel additives into the resin. Notably, the flexural modulus of the materials was not compromised, although a slight reduction in flexural strength associated with the nanogel-modified interphase was observed. Overall, modest amounts of free nanogel additives in the resin phase can be effectively combined with a limited nanogel content filler-resin interphase to lower volumetric shrinkage and dramatically reduce overall polymerization stress of composites.

Temperature-responsive Pickering foams stabilized by poly(N-isopropylacrylamide) nanogels

Poly(N-isopropylacrylamide) (PNIPAM) nanogels were synthesized by emulsion polymerization using sodium dodecyl sulfate (SDS). After removal of SDS by dialysis, the surface tensions of the PNIPAM nanogel aqueous dispersions were measured at various temperatures by the pendant-drop method, and it was found that the surface tensions of the nanogel dispersion below the lower critical solution temperature (LCST) of PNIPAM were much smaller than those of water and comparable to those of the SDS aqueous solution. The stability of the aqueous foams generated by nitrogen bubbling thorough the PNIPAM nanogel dispersion was investigated below and above the LCST of PNIPAM. The foam prepared below the LCST was stable in some degree, whereas almost no foam was formed above the LCST. Moreover, the foam prepared below the LCST was quickly collapsed by changing the temperature above the LCST. This rapid defoaming represents that the surface activity of the PNIPAM nanogel can be switched off by the temperature increase across the LCST.

Synthesis of polyacid nanogels: pH-responsive sub-100 nm particles for functionalisation and fluorescent hydrogel assembly.

Nanogels are crosslinked polymer particles with a swollen size between 1 and 100 nm. They are of major interest for advanced surface coatings, drug delivery, diagnostics and biomaterials. Synthesising polyacid nanogels that show triggered swelling using a scalable approach is a key objective of polymer colloid chemistry. Inspired by the ability of polar surfaces to enhance nanoparticle stabilisation, we report the first examples of pH-responsive polyacid nanogels containing high -COOH contents prepared by a simple, scalable, aqueous method. To demonstrate their functionalisation potential, glycidyl methacrylate was reacted with the -COOH chemical handles and the nanogels were converted to macro-crosslinkers. The concentrated (functionalised) nanogel dispersions retained their pH-responsiveness, were shear-thinning and formed physical gels at pH 7.4. The nanogels were covalently interlinked via free-radical coupling at 37 °C to form transparent, ductile, hydrogels. Mixing of the functionalised nanogels with polymer dots enabled covalent assembly of fluorescent hydrogels.

The stimuli-responsive multiphase behavior of core–shell nanogels with opposite charges and their potential application in in situ gelling system

Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol–gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sol–gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core–shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to −0.33 and 0.082mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value=1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9–2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0wt%, 4-times lower than that of NIA and PND nanogels (about 8.0wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free-standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system.

Developing Cutaneous Applications of Paromomycin Entrapped in Stimuli-Sensitive Block Copolymer Nanogel Dispersions

A new paromomycin micellar nanogel based on poloxamer 407 was developed. In vitro release and ex vivo permeation/retention studies were conducted. In vivo tolerance was assayed by transepidermal water loss. Ex vivo cytotoxicity on RAW and VERO cells and antileishmanial activity on Leishmania promastigotes was tested. The particle size was 9.19 nm (99% loading efficiency) exhibiting Newtonian behavior at 4°C and was pseudoplastic at 25 and 40°C. Drug release followed a Weibull model and the drug remaining in the skin was 31.652 µg/g/cm(2). In vivo tolerance achieved excellent results with negligible cellular toxicity and the best antileishmanial efficiency. The nanogel provided controlled, effective and safe delivery of paromomycin for the treatment of cutaneous leishmaniasis.

Construction of Monomer-free, Highly Crosslinked, Water-compatible Polymers

Polymeric dental adhesives require the formation of densely crosslinked network structures to best ensure mechanical strength and durability in clinical service. Monomeric precursors to these materials typically consist of mixtures of hydrophilic and hydrophobic components that potentially undergo phase separation in the presence of low concentrations of water, which is detrimental to material performance and has motivated significant investigation into formulations that reduce this effect. We have investigated an approach to network formation based on nanogels that are dispersed in inert solvent and directly polymerized into crosslinked polymers. Monomers of various hydrophilic or hydrophobic characteristics were copolymerized into particulate nanogels bearing internal and external polymerizable functionality. Nanogel dispersions were stable at high concentrations in acetone or, with some exceptions, in water and produced networks with a wide range of mechanical properties. Networks formed rapidly upon light activation and reached high conversion with extremely low volumetric shrinkage. Prepolymerizing monomers into reactive nanostructures significantly changes how hydrophobic materials respond to water compared with networks obtained from polymerizations involving free monomer. The modulus of fully hydrated networks formed solely from nanogels was shown to equal or exceed the modulus in the dry state for networks based on nanogels containing a hydrophobic dimethacrylate and hydrophilic monomethacrylate, a result that was not observed in a hydroxyethyl methacrylate (HEMA) homopolymer or in networks formed from nanogels copolymerized with HEMA. These results highlight the unique approach to network development from nanoscale precursors and properties that have direct implications in functional dental materials.

Synthesis and Characterization of Surfactant-Free PDEA/PMAA of IPN Nanogel

Based on the hydrogen bonding between MAA and PDEA, the synthesis of surfactant-free PDEA/PMAA interpenetrating (IPN) nanogels was studied in ultrapure water with N, N-methylene acrylamide (BIS) as a crosslinker, ammonium peroxodisulfate (APS) as an initiator, N,N,N',N'-Tetramethylethylenediamine (TEMED) as an accelerator. First, poly (N, N-diethyl acrylamide) (PDEA) nanogels were synthesized using emulsion precipitation polymerization. As MAA was polymerized in the aqueous dispersion of PDEA nanogels as seeds, PDEA nanogels got interpenetrated with poly (methacrylic acid) (PMAA) due to the effect of the hydrogen bonding between PDEA and PMAA. The chemical structure of the PDEA/PMAA nanogels was studied with Fourier transform infrared (FTIR) spectroscopy. The nanogels morphology was characterized with transmission electron microscopy (TEM) and atomic force microscopy (AFM). And the volume phase transition behaviors and swelling properties were studied with dynamic light scattering (DLS). The experimental results show that the interpenetrating nanogels were very sensitive to temperature. As the amount of MAA increased, the volume of the neutralized PDEA/PMAA nanogels changed less above phase transition temperature and was finally no change. The temperature responsive PDEA/PMAA nanogels will promise to have significant influence on fundamental studies and real applications.

The studies on highly concentrated complex dispersions of gold nanoparticles and temperature-sensitive nanogels and their application as new blood-vessel-embolic materials with high-resolution angiography.

Recently temperature sensitive polymers have been developed as novel embolization materials. However, their flowability and embolization have been seriously impacted by iodine-based X-ray contrast agents. In order to resolve the drawbacks of these contrast agents, highly concentrated complex (HCC) dispersions of gold nanoparticles (GNPs) with p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogels were developed as new blood-vessel-embolic materials with high-resolution angiography. Although GNPs have better X-ray attenuation than iodinated compounds, their poor dispersion stability limits their application in digital subtraction angiography (DSA). HCC dispersions show excellent X-ray attenuation ability which is 2.6 times higher than Omnipaque at 0.31 mol L-1. This can be attributed to the fact that the sol-gel transition of nanogel dispersions improves the colloid stability of GNPs. In the two sol-gel transition temperatures (Tg-s and T's-g) of nanogel dispersions, GNPs have no influence on T's-g, and a great influence on Tg-s. The in vivo experimental data indicate that HCC dispersions show high angiographic ability and good blood-vessel embolization, and can be used for postoperative examination for long periods owing to the entrapment of GNPs into the embolic sites. The HCC dispersions have potential to be developed as new blood-vessel-embolic materials with high-resolution angiography.