Modulation of Methoxyfenozide Release from Lignin Nanoparticles Made of Lignin Grafted with PCL by ROP and Acylation Grafting Methods.

An efficient and sustainable agriculture calls for the development of novel agrochemical delivery systems able to release agrochemicals in a controlled manner. This study investigated the controlled release of the insecticide methoxyfenozide (MFZ) from lignin (LN) nanoparticles (LNPs). LN-grafted poly(ε-caprolactone) (LN-g-PCL) polymers were synthesized using two grafting methods, ring-opening polymerization (ROP)(LN-g-PCLp) and acylation reaction (LN-g-PCLa), creating polymers capable of self-assembling into nanoparticles of different properties, without surfactants. The LN-g-PCLp polymers exhibited a degree of polymerization (DP) from 22 to 101, demonstrating enhanced thermal stability after LN incorporation. LNPs loaded with MFZ exhibited a spherical core-shell structure with a hydrophilic LN outer layer and hydrophobic PCL core, with sizes affected by grafting methods and DP. LNPs controlled MFZ release, displaying variation in release profiles depending on the grafting methodology used, LN-g-PCLp DP, and temperature variations (23 to 30 °C). LNPs formulated with LN-g-PCLa showed a cumulative release of MFZ of 36.78 ± 1.23% over 196 h. Comparatively, increasing the DP of the LN-g-PCLp polymers, a reduction of the LNPs release rate from 92.39 ± 1.46% to 70.59 ± 2.40% was achieved within the same time frame. These findings contribute to identifying ways to modulate the controlled release of agrochemicals by incorporating them in renewable-based LNPs.

Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin.

In this study, we aim to quantify coating uniformity and correlate fluorescence intensity to drug loading for drug-coated angioplasty balloons (DCB) coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin. Uniformity was quantified from histograms and horizontal line profiles of microscopic fluorescent images acquired with sample specific parameters, and cracks in the coating were measured and counted. The fluorescence of images acquired with global parameters was correlated with quercetin loading measured via gravimetric/HPLC analysis. More layers on DCBs may be associated with less uniform coatings, as indicated by differences in histogram standard deviations. The line profile percent deviation from average for each sample was <20%. Cracks were present on all balloons, but their length was not significantly different between samples. The 5-layer DCBs had the fewest cracks, whereas the 15-layer DCBs had the most cracks. A strong positive correlation (R = 0.896) was identified between fluorescence intensity and drug loading. A relationship between the number of layers and coating uniformity seems to exist, but further investigations are required for confirmation. Fluorescence intensity appears to strongly predict drug loading, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.

Effect of Polymeric Nanoparticles with Entrapped Fish Oil or Mupirocin on Skin Wound Healing Using a Porcine Model.

The utilization of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) loaded in collagen-based scaffolds for cutaneous wound healing using a porcine model is unique for the present study. Full-depth cutaneous excisions (5 × 5 cm) on the pig dorsa were treated with pure collagen scaffold (control, C), empty PLGA NPs (NP), FO, mupirocin (MUP), PLGA NPs with entrapped FO (NP/FO) and PLGA NPs with entrapped MUP (NP/MUP). The following markers were evaluated on days 0, 3, 7, 14 and 21 post-excision: collagen, hydroxyproline (HP), angiogenesis and expressions of the COX2, EGF, COL1A1, COL1A3, TGFB1, VEGFA, CCL5 and CCR5 genes. The hypothesis that NP/FO treatment is superior to FO alone and that it is comparable to NP/MUP was tested. NP/FO treatment increased HP in comparison with both FO alone and NP/MUP (day 14) but decreased (p < 0.05) angiogenesis in comparison with FO alone (day 3). NP/FO increased (p < 0.05) the expression of the CCR5 gene (day 3) and tended (p > 0.05) to increase the expressions of the EGF (day 7, day 14), TGFB1 (day 21) and CCL5 (day 7, day 21) genes as compared with NP/MUP. NP/FO can be suggested as a suitable alternative to NP/MUP in cutaneous wound treatment.

Fate of Biodegradable Engineered Nanoparticles Used in Veterinary Medicine as Delivery Systems from a One Health Perspective.

The field of veterinary medicine needs new solutions to address the current challenges of antibiotic resistance and the need for increased animal production. In response, a multitude of delivery systems have been developed in the last 20 years in the form of engineered nanoparticles (ENPs), a subclass of which are polymeric, biodegradable ENPs, that are biocompatible and biodegradable (pbENPs). These platforms have been developed to deliver cargo, such as antibiotics, vaccines, and hormones, and in general, have been shown to be beneficial in many regards, particularly when comparing the efficacy of the delivered drugs to that of the conventional drug applications. However, the fate of pbENPs developed for veterinary applications is poorly understood. pbENPs undergo biotransformation as they are transferred from one ecosystem to another, and these transformations greatly affect their impact on health and the environment. This review addresses nanoparticle fate and impact on animals, the environment, and humans from a One Health perspective.

Topical nanodelivery system of lutein for the prevention of selenite-induced cataract.

Cataracts are responsible for half of the world blindness, surgery being the only viable treatment. Lutein, a naturally occurring carotenoid in the eye, has the potential to reduce cataract progression by protecting the eye from photo-oxidative stress. To restore the eye's natural line of defense against photo-oxidative stress, a formulation was developed using zein and poly(lactic-co-glycolic acid) nanoparticles (NPs) embedded in an optimized bioadhesive thermosensitive gel for the delivery of lutein via topical application. Cataracts were induced in Crl:WI rats via selenite injection at 13 days post-partum, followed by 7 days of treatment with free lutein or lutein-loaded NPs administered orally or topically. Cataract severity was significantly reduced in rats treated with topical applications of lutein-loaded NPs compared to the positive control, while no significant differences were observed in rats treated with other lutein formulations including oral and topically applied free lutein.

Zein Nanoparticles Uptake by Hydroponically Grown Soybean Plants.

In the interest of developing and characterizing a polymeric nanoparticle pesticide delivery vehicle to soybeans, zein nanoparticle (ZNP) uptake by the roots and biodistribution to the leaves of soybean plants was measured. Zein was tagged with fluorescein isothiocyanate (FITC) and made into nanoparticles (135 ± 3 nm diameter. 0.202 ± 0.034 PDI and 81 ± 4 mV zeta-potential at pH 6) using an emulsion-diffusion method. After 10 days of hydroponic exposure, association between particles and roots of plants was found to vary based on bulk nanoparticle concentration. While 0.37 mg NP/mg dry weight were detected in roots immersed in 0.88 mg NP/mL nanoparticle suspension, 0.58 mg NP/mg dry weight associated with roots immersed in a high dose nanoparticle suspension of 1.75 mg NP/mL at 10 days. Nanoparticle root uptake followed second order kinetics. A small amount of increased fluorescence was detected in the hydroponically exposed plant's leaves, suggesting that either small amounts of particles or other fluorescent contaminants of zein were up taken by the roots and biodistributed within the plant. To the authors' knowledge, this is the first study in which the uptake and time-dependent association between polymeric nanoparticles and soybeans are quantified.

Delivery of florfenicol in veterinary medicine through a PLGA-based nanodelivery system: improving its performance and overcoming some of its limitations.

As is the case with other veterinary antibiotics, florfenicol (FFC) faces certain limitations, such as low solubility in water, or the fact that it is reported to interfere with the immune response after some immunoprofilactic actions in livestock. Aiming to improve its efficacy and overall performance, FFC was loaded into a polymeric nanobased delivery system by succesfully using the emulsion-evaporation technique. The poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with FFC were characterized in terms of size (101 ± 0.52 nm), zeta potential (26.80 ± 1.30 mV) and poly-dispersity index (0.061 ± 0.019). The achieved loading was 2.24 µg FFC/mg of NPs, with an entrapment efficiency of 7.9%. The antimicrobial effect, the anti-biofilm formation and the cytotoxicity properties of the NPs were evaluated. The results indicated a MIC decreased by ~97.13% for S. aureus, 99.33% for E.coli and 64.1% for P. aeruginosa when compared to free FFC. The minimum inhibitory concentration (MIC) obtained indicated the potential for using a significantly lower dose of florfenicol. The delivery system produced biofilm inhibition while showing no cytotoxic effects when tested on porcine primary fibroblasts and horse mesenchymal stem cells. These findings suggest that florfenicol can be improved and formulations optimized for use in veterinary medicine through its incorporation into a nanobased delivery system designed to release in a controlled manner over time.

Method for assessing coating uniformity of angioplasty balloons coated with poly(lactic-co-glycolic acid) nanoparticles loaded with quercetin.

Significance: Drug-coated angioplasty balloons (DCBs) are used to treat peripheral artery disease, and proper dosage depends on coating characteristics like uniformity and number of layers. Aim: Quantify coating uniformity and correlate fluorescence intensity to drug loading for DCBs coated with 5, 10, 15, or 20 layers of poly(lactic-co-glycolic acid) nanoparticles (NPs) entrapped with quercetin. Approach: Images of DCBs were acquired using fluorescence microscopy. Coating uniformity was quantified from histograms and horizontal line profiles, and cracks on the balloons were measured and counted. Fluorescence intensity was correlated with the drug loading of quercetin found from gravimetric analysis coupled with high-performance liquid chromatography (HPLC). Results: Higher numbers of coating layers on DCBs may be associated with less uniform coatings. Cracks in the coating were present on all balloons, and the length of cracks was not significantly different between balloons coated with different numbers of layers or balloons coated with the same number of layers. A strong positive correlation was identified between fluorescence intensity and drug loading. Conclusion: There may be a relationship between the number of NP layers and the uniformity of the coating, but further investigation is needed to confirm this. Fluorescence intensity appears to be a strong predictor of drug loading on DCBs coated with quercetin-entrapped NPs, demonstrating that fluorescent imaging may be a viable alternative to drug release studies.

Elucidating the insecticidal mechanisms of zein nanoparticles on Anticarsia gemmatalis (Lepidoptera: Erebidae).

Previous research suggested that positively charged zein nanoparticles [(+)ZNP] were toxic to neonates of Anticarsia gemmatalis Hübner and deleterious to noctuid pests. However, specific modes of action for ZNP have not been elucidated. Diet overlay bioassays attempted to rule out the hypothesis that A. gemmatalis mortality was caused by surface charges from component surfactants. Overlay bioassays indicated that negatively charged zein nanoparticles [(-)ZNP] and its anionic surfactant, sodium dodecyl sulfate (SDS), exhibited no toxic effects when compared to the untreated check. Nonionic zein nanoparticles [(N)ZNP] appeared to increase mortality compared to the untreated check, though larval weights were unaffected. Overlay results for (+)ZNP and its cationic surfactant, didodecyldimethylammonium bromide (DDAB), were found to be consistent with former research indicating high mortalities, and thus, dosage response curves were conducted. Concentration response tests found the LC50 for DDAB on A. gemmatalis neonates was 208.82 a.i./ml. To rule out possible antifeedant capabilities, dual choice assays were conducted. Results indicated that neither DDAB nor (+)ZNP were antifeedants, while SDS reduced feeding when compared to other treatment solutions. Oxidative stress was tested as a possible mode of action, with antioxidant levels used as a proxy for reactive oxygen species (ROS) in A. gemmatalis neonates, which were fed diet treated with different concentrations of (+)ZNP and DDAB. Results indicated that both (+)ZNP and DDAB decreased antioxidant levels compared to the untreated check, suggesting that both (+)ZNP and DDAB may inhibit antioxidant levels. This paper adds to the literature on potential modes of action by biopolymeric nanoparticles.

Injectable Antioxidant and Oxygen-Releasing Lignin Composites to Promote Wound Healing.

The application of engineered biomaterials for wound healing has been pursued since the beginning of tissue engineering. Here, we attempt to apply functionalized lignin to confer antioxidation to the extracellular microenvironments of wounds and to deliver oxygen from the dissociation of calcium peroxide for enhanced vascularization and healing responses without eliciting inflammatory responses. Elemental analysis showed 17 times higher quantity of calcium in the oxygen-releasing nanoparticles. Lignin composites including the oxygen-generating nanoparticles released around 700 ppm oxygen per day at least for 7 days. By modulating the concentration of the methacrylated gelatin, we were able to maintain the injectability of lignin composite precursors and the stiffness of lignin composites suitable for wound healing after photo-cross-linking. In situ formation of lignin composites with the oxygen-releasing nanoparticles enhanced the rate of tissue granulation, the formation of blood vessels, and the infiltration of α-smooth muscle actin+ fibroblasts into the wounds over 7 days. At 28 days after surgery, the lignin composite with oxygen-generating nanoparticles remodeled the collagen architecture, resembling the basket-weave pattern of unwounded collagen with minimal scar formation. Thus, our study shows the potential of functionalized lignin for wound-healing applications requiring balanced antioxidation and controlled release of oxygen for enhanced tissue granulation, vascularization, and maturation of collagen.

Life History of Chrysodeixis includens (Lepidoptera: Noctuidae) on Positively Charged Zein Nanoparticles.

Research indicates that nanoparticles can be an effective agricultural pest management tool, though unintended effects on the insect must be evaluated before their use in agroecosystems. Chrysodeixis includens (Walker) was used as a model to evaluate chronic parental and generational exposure to empty, positively charged zein nanoparticles ((+)ZNP) and methoxyfenozide-loaded zein nanoparticles (+)ZNP(MFZ) at low-lethal concentrations. To determine concentration limits, an acute toxic response test on meridic diet evaluated (+)ZNP(MFZ) and technical grade methoxyfenozide using two diet assay techniques. No differences in acute toxicity were observed between the two treatments within their respective bioassays. With these results, population dynamics following chronic exposure to low-lethal concentrations were evaluated. Parental lifetables evaluated cohorts of C. includens reared on diet treated with LC5 equivalents of (+)ZNP, (+)ZNP(MFZ), or technical grade methoxyfenozide. Compared to technical grade methoxyfenozide, (+)ZNP(MFZ) lowered both the net reproductive rate and intrinsic rate of increase, and was more deleterious to C. includens throughout its lifespan. This was contrasted to (+)ZNP, which showed no differences in population dynamics when compared with the control. To evaluate chronic exposure to (+)ZNP, generational lifetables reared cohorts of C. includens on LC5 equivalent values of (+)ZNP and then took the resulting offspring to be reared on either (+)ZNP or untreated diet. No differences in lifetable statistics were observed between the two treatments, suggesting that (+)ZNP at low ppm do not induce toxic generational effects. This study provides evidence into the effects of nanodelivered methoxyfenozide and the generational impact of (+)ZNP.

Distinguishing nanoparticle drug release mechanisms by asymmetric flow field-flow fractionation.

This research demonstrates the development, application, and mechanistic value of a multi-detector asymmetric flow field-flow fractionation (AF4) approach to acquire size-resolved drug loading and release profiles from polymeric nanoparticles (NPs). AF4 was hyphenated with multiple online detectors, including dynamic and multi-angle light scattering for NP size and shape factor analysis, fluorescence for drug detection, and total organic carbon (TOC) to quantify the NPs and dissolved polymer in nanoformulations. The method was demonstrated on poly(lactic-co-glycolic acid) (PLGA) NPs loaded with coumarin 6 (C6) as a lipophilic drug surrogate. The bulk C6 release profile using AF4 was validated against conventional analysis of drug extracted from the NPs and complemented with high performance liquid chromatography - quadrupole time-of-flight (HPLC-QTOF) mass spectrometry analysis of oligomeric PLGA species. Interpretation of the bulk drug release profile was ambiguous, with several release models yielding reasonable fits. In contrast, the size-resolved release profiles from AF4 provided critical information to confidently establish the release mechanism. Specifically, the C6-loaded NPs exhibited size-independent release rate constants and no significant NP size or shape transformations, suggesting surface desorption rather than diffusion through the PLGA matrix or erosion. This conclusion was supported through comparative experimental evaluation of PLGA NPs carrying a fully entrapped drug, enrofloxacin, which showed size-dependent diffusive release, along with density functional theory (DFT) calculations indicating a higher adsorption affinity of C6 onto PLGA. In summary, the development of the size-resolved AF4 method and data analysis framework fulfills salient analytical gaps to determine drug localization and release mechanisms from nanomedicines.

Nanoparticle coatings for controlled release of quercetin from an angioplasty balloon.

Peripheral artery disease (PAD) is a systemic vascular disease of the legs that results in a blockage of blood flow from the heart to the lower extremities. Now one of the most common causes of mortality in the U.S., the first line of therapy for PAD is to mechanically open the blockages using balloon angioplasty. Coating the balloons with antiproliferative agents can potentially reduce vessel re-narrowing, or restenosis after surgical intervention, but current drug-coated balloons releasing chemotherapy agents like paclitaxel have in some cases shown increased mortality long-term. Our aim was to design a novel drug-coated balloon using a polymeric nanodelivery system for a sustained release of polyphenols that reduce restenosis but with reduced toxicity compared to chemotherapy agents. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles with entrapped quercetin, a dimethoxy quercetin (rhamnazin), as well as quercetin covalently attached to PLGA, were developed. Balloon catheters were coated with polymeric nanoparticles using an ultrasonic method, and nanoparticle characteristics, drug loading, coating uniformity and drug release were determined. The adhesion of nanoparticles to vascular smooth muscle cells and the antiproliferative effect of nano-delivered polyphenols were also assessed. Of the nanoparticle systems tested, those with covalently attached quercetin provided the most sustained release over a 6-day period. Although these particles adhered to cells to a smaller extent compared to other nanoparticle formulations, their attachment was resistant to washing. These particles also exhibited the greatest anti-proliferative effect. In addition, their attachment was not altered when the cells were grown in calcifying conditions, and in PAD tissue calcification is typically a condition that impedes drug delivery. Moreover, the ultrasonic coating method generated a uniform balloon coating. The polymeric nanoparticle system with covalently attached quercetin developed herein is thus proposed as a promising platform to reduce restenosis post-angioplasty.

Stability and ocular biodistribution of topically administered PLGA nanoparticles.

Polymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye.

Asymmetric flow field-flow fractionation (AF4) with fluorescence and multi-detector analysis for direct, real-time, size-resolved measurements of drug release from polymeric nanoparticles.

Polymeric nanoparticles (NPs) are typically designed to enhance the efficiency of drug delivery by controlling the drug release rate. Hence, it is critical to obtain an accurate drug release profile. This study presents the first application of asymmetric flow field-flow fractionation (AF4) with fluorescence detection (FLD) to quantify release profiles of fluorescent drugs from polymeric NPs, specifically poly(lactic-co-glycolic acid) NPs loaded with enrofloxacin (PLGA-Enro NPs). In contrast to conventional measurements requiring separation of the NPs and dissolved drugs (typically by dialysis) prior to quantification, AF4 provides in situ removal of unincorporated drugs, while the judicious combination of online FLD and UV detection selectively provides the entrapped drug and PLGA NP concentrations, respectively, and hence the drug loading. NP size and shape factors are simultaneously obtained by online dynamic and multi-angle light scattering (DLS, MALS) detectors. The AF4 and dialysis approaches were compared to evaluate drug release from PLGA-Enro NPs containing a high proportion (≈ 94%) of unincorporated (burst release) drug at three temperatures spanning the glass transition temperature (Tg ≈ 33 °C) of the NPs. The AF4 method clearly captured the temperature dependence of the drug release relative to Tg (from no release at 20 °C to rapid release at 37 °C). In contrast, dialysis was not able to distinguish differences in the extent or rate of release of the entrapped drug because of interferences from the burst release, as well as the dialysis lag time, as supported through a diffusion model and validation experiments on purified NPs with low burst release. Finally, the multi-detector AF4 analysis yielded unique size-dependent release profiles across the entire NP size distribution, with smaller NPs showing faster release consistent with radial diffusion from the NPs. Overall, this study demonstrates the novel application and advantages of multi-detector AF4 methods, particularly AF4-FLD, to obtain direct, size-resolved release profiles of fluorescent drugs from polymeric NPs.

Prevention of infection caused by enteropathogenic E. coli O157:H7 in intestinal cells using enrofloxacin entrapped in polymer based nanocarriers.

Poor bioavailability of antibiotics, toxicity, and development of antibiotic-resistant bacteria jeopardize antibiotic treatments. To circumvent these issues, drug delivery using nanocarriers are highlighted to secure the future of antibiotic treatments. This work investigated application of nanocarriers, to prevent and treat bacterial infection, presenting minimal toxicity to the IPEC-J2 cell line. To accomplish this, polymer-based nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and lignin-graft-PLGA (LNP) loaded with enrofloxacin (ENFLX) were synthesized, yielding spherical particles with average sizes of 111.8 ± 0.6 nm (PLGA) and 117.4 ± 0.9 nm (LNP). The releases of ENFLX from PLGA and LNP were modeled by a theoretical diffusion model considering both the NP and dialysis diffusion barriers for drug release. Biocompatible concentrations of ENFLX, enrofloxacin loaded PLGA(Enflx) and LNP(Enflx) were determined based on examination of bacterial inhibition, toxicity, and ROS generation. Biocompatible concentrations were used for treatment of higher- and lower-level infections in IPEC-J2 cells. Prevention of bacterial infection by LNP(Enflx) was enhanced more than 50% compared to ENFLX at lower-level infection. At higher-level infection, PLGA(Enflx) and LNP(Enflx) demonstrated 25% higher prevention of bacteria growth compared to ENFLX alone. The superior treatment achieved by the nanocarried drug is accredited to particle uptake by endocytosis and slow release of the drug intracellularly, preventing rapid bacterial growth inside the cells.

Effects of engineered lignin-graft-PLGA and zein-based nanoparticles on soybean health.

The majority of published research on the effect of engineered nanoparticles on terrestrial plant species is focused on inorganic nanoparticles, with the effects of organic polymeric nanoparticles (NP) on plants remaining largely unexplored. It is critical to understand the impact of polymeric NPs on plants if these particles are to be used as agrochemical delivery systems. This study investigates the effect of biodegradable polymeric lignin-based nanoparticles (LNPs) and zein nanoparticles (ZNP) on soybean plant health. The LNPs (114 ± 3.4 nm, -53.8 ± 6.9 mV) were synthesized by emulsion evaporation from lignin-graft-poly(lactic-co-glycolic) acid, and ZNPs (142 ± 3.9 nm and + 64.5 ± 4.7 mV) were synthesized by nanoprecipitation. Soybeans were grown hydroponically and treated with 0.02, 0.2, and 2 mg/ml of LNPs or ZNPs at 28 days after germination. Plants were harvested after 1, 3, 7 and 14 days of particle exposure and analyzed for root and stem length, chlorophyll concentration, dry biomass of roots and stem, nutrient uptake and plant ROS. Root and stem length, chlorophyll and stem biomass did not differ significantly between treatments and controls for LNPs-treated plants at all concentrations, and at low doses of ZNPs. At 2 mg/ml ZNPs, the highest concentration tested, after 7 days of treatment chlorophyll levels and root biomass increased and stem length was reduced in comparison to the control. Nutrient uptake was largely unaffected at 0.02 and 0.2 mg/ml NPs. A concentration-dependent increase in the oxidative stresss was detected, especially in the ZNP treated plants. Overall, LNPs and ZNPs had a minimum impact on soybean health especially at low and medium doses. To our knowledge this is the first study to show the effect of zein and lignin based polymeric NPs designed for agrochemical delivery on soybean plant health.

Elucidating Efficacy of Ingested Positively Charged Zein Nanoparticles Against Noctuidae.

A meridic diet overlay bioassay using empty, positively charged zein nanoparticles ((+)ZNP) was performed on soybean looper (Chrysodeixis includens (Walker)), tobacco budworm (Heliothis virescens (F.)), and velvetbean caterpillar (Anticarsia gemmatalis Hübner) (Lepidoptera: Noctuidae). Assessment of effects on mortality and development weights 7 d after ingestion of (+)ZNP were evaluated on larvae of each species. Treatments involved different concentrations, with H. virescens and A. gemmatalis offered 0 and 3,800 ppm (+)ZNP, whereas C. includens colonies were offered 0, 630, 1,260, and 2,520 ppm (+)ZNP. Mortality of A. gemmatalis and C. includens increased after ingestion of the highest (+)ZNP concentrations, while H. virescens neonate mortality was unaffected. Neonate and third-instar weights of A. gemmatalis and C. includens, and neonate H. virescens, decreased with high (+)ZNP concentrations. Following mortality results from A. gemmatalis neonates, a concentration response test was performed using a range of (+)ZNP concentrations. The LC50 for A. gemmatalis was 1,478 ppm. The potential of (+)ZNP as a pest management tactic is discussed.

Lignin-Graft-Poly(lactic-co-glycolic) Acid Biopolymers for Polymeric Nanoparticle Synthesis.

A lignin-graft-poly(lactic-co-glycolic) acid (PLGA) biopolymer was synthesized with two types of lignin (LGN), alkaline lignin (ALGN) and sodium lignosulfonate (SLGN), at different (A/S)LGN/PLGA ratios (1:2, 1:4, and 1:6 w/w). 1H NMR and Fourier-transform infrared spectroscopy (FT-IR) confirmed the conjugation of PLGA to LGN. The (A/S)LGN-graft-PLGA biopolymers were used to form nanodelivery systems suitable for entrapment and delivery of drugs for disease treatment. The LGN-graft-PLGA NPs were generally small (100-200 nm), increased in size with the amount of PLGA added, monodisperse, and negatively charged (-48 to -60 mV). Small-angle scattering data showed that particles feature a relatively smooth surface and a compact spherical structure with a distinct core and a shell. The core size and shell thickness varied with the LGN/PLGA ratio, and at a 1:6 ratio, the particles deviated from the core-shell structure to a complex internal structure. The newly developed (A/S)LGN-graft-PLGA NPs are proposed as a potential delivery system for applications in biopharmaceutical, food, and agricultural sectors.

Lignin-graft-PLGA drug-delivery system improves efficacy of MEK1/2 inhibitors in triple-negative breast cancer cell line.

Aim: Few targeted therapies are available for triple-negative breast cancer (TNBC) patients. Here, we propose a novel alkaline-lignin-conjugated-poly(lactic-co-glycolic acid) (L-PLGA) nanoparticle drug delivery system to improve the efficacy of targeted therapies. Materials & methods: L-PLGA nanoparticles (NPs) loaded with the MEK1/2 inhibitor GDC-0623 were characterized, tested in vitro on MDA-MB-231 TNBC cell line and compared with loaded PLGA NPs. Results: Loaded L-PLGA NPs were less than half the size of PLGA NPs, had slower drug release and improved the efficacy of GDC-0623 when tested in vitro. We demonstrated that GDC-0623 reversed epithelial-to-mesenchymal transition in TNBC. Conclusion: Our findings indicate that L-PLGA NPs are superior to PLGA NPs in delivering GDC-0623 to cancer cells for improved efficacy in vitro.