Nanoprecipitation Method Research Articles

Recyclable Biomass-Derived Polyethylene-Like Materials as Functional Coatings for Commercial Fabrics: Toward Upcycling of Waste Textiles

Bio-based polymers are recognized as promising alternatives to fossil-based counterparts. However, the inferior material performance of bio-based polymers is a serious restriction to their application fields. Herein, renewable polyethylene-like materials (PLMs) are used as surface coatings for commercial fabrics. First, α,ω-diene monomers were synthesized by the downstream products of sugar and castor oil derivatives. Subsequently, biomass-derived polymers were generated via acyclic diene metathesis (ADMET) (co)polymerization of these monomers followed by exhaustive hydrogenation. The obtained long-chain aliphatic polyesters are considered remarkable polyethylene mimics in that these hydrophobic and semicrystalline materials show unique features such as hydrolysis resistance and recyclability. On the other hand, PLM nanoparticles were prepared by the nanoprecipitation method and then drop-cast on commercial fabric surfaces. Hydrophobically modified fabrics show repellency to various water droplets and the capability of oil/water separation as well as anti-icing and anticorrosive characteristics. Moreover, photoinduced contaminant removal and wettability change are realized by fabrics with a hybrid coating layer composed of PLM and titanium dioxide (TiO2) nanoparticles. These polyethylene-mimetic materials not only meet the requirements of sustainability in terms of renewability and recyclability but also show great prospects in surface functionalization of commercial fabrics and upcycling of waste textiles.

Preparation of Wide-Domain pH Color-Changing Nanocapsules and Application in Hydrogel Fibers.

In recent years, there has been an increase in demand for pH color-changing materials. These materials can visually communicate signals to people by connecting pH changes with color information. Embedding pH indicators into fibers to create flexible color-changing materials is an effective way to develop daily wearable products. For the stability of the indicator and the indirect contact of the indicator with the human body, it is usually necessary to encapsulate it in capsules. In this study, different pH indicators (Thymol Blue-TB, Bromocresol Green-BCG, and Bromocresol Purple-BCP) were mixed into a wide-domain pH color-changing indicator and encapsulated with ethyl cellulose (EC) by the flash nanoprecipitation (FNP) method using a new-type droplet-shaped confined impinging jet mixer. The effects of flow rate, core-to-wall ratio, and mixed solution concentration on the formation of the nanocapsules were investigated. In addition, the morphology, particle size, size distribution, dispersion stability, and encapsulation efficiency were systematically studied. At a core-to-wall ratio of 1:2, a mixed solution with a concentration of 6 mg/mL and a feed flow rate of 40 mL/min produced nanocapsules with an average particle size of 141.83 ± 0.98 nm and a PDI of 0.125 ± 0.01. Furthermore, a zeta potential with a range of -31.83 ± 0.23 mV and an encapsulation efficiency of 75.20 ± 1.72% were observed at 1:2 core-to-wall ratios. It was concluded that the color of the nanocapsules continuously changed from yellow to green and green to blue when the pH range was increased from 3 to 10. The color-changing nanocapsules were then embedded into sodium alginate hydrogel fibers, resulting in the same color-changing trend (pH 3-10) as that obtained for the nanocapsules. This study can be useful for the pH monitoring of various body fluids, such as wound exudate, urine, and sweat.

Polylactide Nanoparticles as a Biodegradable Vaccine Adjuvant: A Study on Safety, Protective Immunity and Efficacy against Human Leishmaniasis Caused by Leishmania Major.

Leishmaniasis is the 3rd most challenging vector-borne disease after malaria and lymphatic filariasis. Currently, no vaccine candidate is approved or marketed against leishmaniasis due to difficulties in eliciting broad immune responses when using sub-unit vaccines. The aim of this work was the design of a particulate sub-unit vaccine for vaccination against leishmaniasis. The poly (D,L-lactide) nanoparticles (PLA-NPs) were developed in order to efficiently adsorb a recombinant L. major histone H2B (L. major H2B) and to boost its immunogenicity. Firstly, a study was focused on the production of well-formed nanoparticles by the nanoprecipitation method without using a surfactant and on the antigen adsorption process under mild conditions. The set-up preparation method permitted to obtain H2B-adsorbed nanoparticles H2B/PLA (adsorption capacity of about 2.8% (w/w)) with a narrow size distribution (287 nm) and a positive zeta potential (30.9 mV). Secondly, an in vitro release assay performed at 37 °C, pH 7.4, showed a continuous release of the adsorbed H2B for almost 21 days (30%) from day 7. The immune response of H2B/PLA was investigated and compared to H2B + CpG7909 as a standard adjuvant. The humoral response intensity (IgG) was substantially similar between both formulations. Interestingly, when challenged with the standard parasite strain (GLC94) isolated from a human lesion of cutaneous leishmaniasis, mice showed a significant reduction in footpad swelling compared to unvaccinated ones, and no deaths occurred until week 17th. Taken together, these results demonstrate that PLA-NPs represent a stable, cost-effective delivery system adjuvant for use in vaccination against leishmaniasis.

Synthesis of Organic Semiconductor Nanoparticles with Different Conformations Using the Nanoprecipitation Method.

In recent years, nanoparticulate materials have aroused interest in the field of organic electronics due to their high versatility which increases the efficiency of devices. In this work, four different stable conformations based on the organic semiconductors P3HT and PC71BM were synthesized using the nanoprecipitation method, including blend and core-shell nanoparticles. All nanoparticles were obtained free of surfactants and in aqueous suspensions following the line of ecologically correct routes. The structural and optoelectronic properties of the nanoparticles were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-visible absorption spectroscopy and UV-visible photoluminescence (PL). Even in aqueous media, the blend and core-shell nanoparticles exhibited a greater light absorption capacity, and these conformations proved to be effective in the process of dissociation of excitons that occurs at the P3HT donor/PC71BM acceptor interface. With all these characteristics and allied to the fact that the nanoparticles are surfactant-free aqueous suspensions, this work paves the way for the use of these colloids as a photoactive layer of organic photovoltaic devices that interface with biological systems.

Nanotechnology approach for exploring the enhanced bioactivities, biochemical characterisation and phytochemistry of freshly prepared Mentha arvensis L. nanosuspensions.

Mentha arvensis L. is the most valuable medicinal plant that possesses anti-inflammatory, hepatoprotective, antimicrobial, and antioxidant properties. There are few studies available in the literature about M. arvensis L nanoparticles, but their nanosuspensions-based information remains unclear and needs further study. This study was designed to explore the nanotechnology approach for biochemical characterisation, enhanced bioactivities, and photochemistry of freshly prepared M. arvensis L. nanosuspensions. Nanosuspensions of M. arvensis L. leaves were prepared by following the nanoprecipitation method. In this study, we performed structural and biochemical characterisation through analyses of Fourier-transform infrared (FTIR) spectroscopy, high-performance liquid chromatography (HPLC), phase contrast microscopy and enhanced bioactivities; antioxidant, alpha-amylase inhibition, glycation inhibition and cytotoxicity assays. FTIR analysis revealed the presence of phenols, amines hydroxyl, carboxylic acid, alkenes, alkenes and alkynes. HPLC analysis revealed the presence of chlorogenic acid, a principal phenolic component. Biofilm inhibition activity revealed that the growth formation of Escherichia coli inhibited up to 62.4% and 53.35% by leaves extract and nanosuspension, respectively. However, the growth of Staphylococcus aureus was not inhibited by nanosuspension and extract. Nanosuspension and extract exhibited 155.92 mg, 108.11 mg gallic acids per 100 g of dry weight total phenolic content and 233.44 mg, 163.933 mg catechin per 100 g of dried weight total flavonoid content in extract and nanosuspension, respectively. Antioxidant activity revealed the scavenging potential of nanosuspensions and extract was 41.01% and 12.07%, respectively. Alpha-amylase inhibiting activity of nanosuspension and extract was 36% and 33%, while, the antiglycation potential of nanosuspension and extract were 41.68% and 35.18%, respectively. Nanosuspensions and extract showed maximum hemolytic activity at 12.91% and 17.18%, respectively. These cost-effective nanoformulations could serve as a platform for therapeutic purposes in controlling the high risk of infectious diseases and designing efficient plant nanosuspensions by discovering novel bioactive compounds in an adequate manner.

Vitamin E-loaded polymeric nanoparticles from biocompatible adipate-based copolymer obtained using the nanoprecipitation method

An enzymatic synthesis of new aliphatic biopolyesters - poly(butylene adipate)-co-(dilinol adipate) (PBA-DLA) with the use of monomers obtained from natural sources was carried out. Lipase B from the strain Candida antarctica (CALB) was used as a biocatalyst. The chemical structure of the PBA-DLA copolyester was confirmed by 1H NMR. In vitro biological studies did not show its cytotoxic effect on mouse fibroblast cells. PBA-DLA nanoparticles obtained in a single-stage nanoprecipitation process were used to encapsulate hydrophobic α-tocopherol (α-TP), the main component of vitamin E, obtaining an encapsulation efficiency of 48−74% (EE%) depending on the concentration of α-TP (2.5 ; 5; 10 mg/ml), which was confirmed by dynamic light scattering (DLS) analysis, ultraviolet spectroscopy (UV-VIS) and 1H NMR.

Formation and Characterization of Oregano Essential Oil Nanocapsules Applied onto Polyester Textile

Oregano essential oil was encapsulated in poly-ϵ-caprolactone nanoparticles by a nanoprecipitation method using glycerin as a moisturizer. Nanocapsule characterization was performed by measuring the particle size, colloidal stability and encapsulation efficiency using dynamic light scattering, UV-Vis spectrophotometry and scanning electron microscopy (SEM). The nanoparticles had a mean particle size of 235 nm with a monomodal distribution. In addition, a low polydispersity index was obtained, as well as a negative zeta potential of -36.3 mV and an encapsulation efficiency of 75.54%. Nanocapsules were applied to polyester textiles through bath exhaustion and foulard processing. Citric acid and a resin were applied as crosslinking agents to improve the nanocapsules' adhesion to the fabric. The adsorption, desorption, moisture content and essential oil extraction were evaluated to determine the affinity between the nanocapsules and the polyester. The adsorption was higher when the citric acid and the resin were applied. When standard oregano nanocapsules were used, almost all of the impregnated nanoparticles were removed when washed with water. The moisture content was evaluated for treated and non-treated textiles. There was a significant increase in the moisture content of the treated polyester compared to the non-treated polyester, which indicates that the polyester hydrophilicity increased with an important absorption of the essential oil nanocapsules; this can improve fabric comfort and probably promote antibacterial properties.

Uptake of Cationic PAMAM-PLGA Nanoparticles by the Nasal Mucosa

Nanoparticles provide promising advantages in advanced delivery systems for enhanced drug delivery and targeting. The use of a biodegradable polymer such as PLGA (poly lactic-co-glycolic acid) promotes improved nanoparticle safety and, to some extent, provides the ability to modify nanoparticle surface properties. This study compared the effect of altering the surface charge on the translocation of PLGA nanoparticles across excised nasal mucosal tissues. Nanoparticles (average diameter of 60–100 nm) loaded with Nile Red (lipophilic fluorescent dye) were fabricated using a nanoprecipitation method. The effects of nanoparticle surface charge were investigated by comparing the transfer of untreated nanoparticles (negatively charged) and positively charged PLGA nanoparticles, which were modified using PAMAM dendrimer (polyamidoamine, 5th generation). All nanoparticles were able to be transferred in measurable quantities into both nasal respiratory and olfactory mucosae within 30 min. The total nanoparticle uptake was less than 5% of the nanoparticle mass exposed to the tissue surface. The cationic nanoparticles showed a significantly lower transfer into the mucosal tissues where the amount of nanoparticles transferred was 1.8–4-fold lower compared to the untreated negatively charged nanoparticles. The modification of the nanoparticle surface charge can alter the nanoparticle interaction with the nasal epithelial surface, which can result in decreasing the nanoparticle transfer into the nasal mucosa.

Water-dispersed semiconducting polymer for NIR-II fluorescence imaging and NIR-II laser-triggered photothermal therapy

Fluorescence imaging in the second near-infrared (NIR-II) window has emerged as a promising imaging method for cancer diagnosis because of its superior properties such as deep penetration depth and high signal to background ratio. The integration of NIR-II imaging and NIR-II photothermal therapy (PTT) has shown great potential in the field of biomedical research and preclinical practice. Semiconducting polymers have several featured advantages, such as easily tunable optical properties, high photostability, and reliable biocompatibility. However, most semiconducting polymer nanoparticles (SPNs) formed using nanoprecipitation method have high accumulation in reticulum endoplasmic system (RES), and their maximum absorption is located in the first near-infrared (NIR-I) window. Therefore, it is required to develop new NIR-II emissive SPNs with the absorption peaks over 1000 nm, which can be triggered by NIR-II light for deep tissue PTT. Herein, we develop an amphiphilic semiconducting polymer (ASP) with the maximum absorption located in the NIR-II window. The amphiphilic feature of ASP drives it to self-assemble into nanoparticles in aqueous media, which show excellent optical properties, low toxicity, and proper size. ASP exhibits not only bright NIR-II fluorescence but also prominent photothermal performance under 1064 nm laser irradiation. Impressively, ASP shows superior accumulation ability in the tumor compared with that in liver or spleen. Taken together, the overall properties of ASP make it a promising NIR-II phototheranostic agent for cancer diagnosis and treatment.

Galactosylated Polymer/Gold Nanorods Nanocomposites for Sustained and Pulsed Chemo-Photothermal Treatments of Hepatocarcinoma.

In this paper, we propose a rational design of a hybrid nanosystem capable of locally delivering a high amount of hydrophobic anticancer drugs (sorafenib or lenvatinib) and heat (hyperthermia) in a remote-controlled manner. We combined in a unique nanosystem the excellent NIR photothermal conversion of gold nanorods (AuNRs) with the ability of a specially designed galactosylated amphiphilic graft copolymer (PHEA-g-BIB-pButMA-g-PEG-GAL) able to recognize hepatic cells overexpressing the asialoglycoprotein receptor (ASGPR) on their membranes, thus giving rise to a smart composite nanosystem for the NIR-triggered chemo-phototherapy of hepatocarcinoma. In order to allow the internalization of AuNRs in the hydrophobic core of polymeric nanoparticles, AuNRs were coated with a thiolated fatty acid (12-mercaptododecanoic acid). The drug-loaded hybrid nanoparticles were prepared by the nanoprecipitation method, obtaining nanoparticles of about 200 nm and drug loadings of 9.0 and 5.4% w/w for sorafenib and lenvatinib, respectively. These multifunctional nanosystems have shown to convert NIR radiation into heat and release charged drugs in a remote-controlled manner. Then, the biocompatibility and synergistic effects of a chemo-phototherapy combination, as well the receptor-mediated internalization, were evaluated by an in vitro test on HepG2, HuH7, and NHDF. The results indicate that the proposed nanoparticles can be considered to be virtuous candidates for an efficient and selective dual-mode therapy of hepatocarcinoma.

Characterization of controlled-release Eucalyptus citriodora oil/Zinc ions nanoparticles with enhanced antibacterial properties against E. coli O157:H7 in fruit juice

Eucalyptus citriodora oil (ECO) has excellent antibacterial properties, but its application is limited due to its volatility and lack of antimicrobial targeting properties. Zinc ions are metal ions on which the active center of metalloproteinases depend and have antibacterial functions. This study aimed to prepare nanoparticles against Escherichia coli O157:H7 (E. coli O157:H7) by encapsulating ECO in zein with nano-precipitation method, and chelating zinc metal ions with electrostatic interaction to improve the stability, controlled-release ability and antibacterial ability of nanoparticles. Herein, the antibacterial mechanism of ECO against E. coli O157:H7 was investigated from the molecular level. The results of molecular docking showed that ECO inhibited the activity of G6PDH in respiratory metabolism pathway (hexose monophophate pathway), and also inhibited the DNA polymerase. Furthermore, we demonstrated that the controlled-release nanoparticles (ECO/Zn2+-loaded NPT) possessed suitable particle size (275.43 nm), poly dispersity index (PDI, 0.254), zeta potential (-31.12 mV) and chelation rate (42.3 %). The results of Fourier Transform Infrared spectrometer (FT-IR), and Raman spectrum confirmed that ECO was successfully encapsulated in the nanoparticles. Meanwhile, the results of antibacterial experiments showed that ECO/Zn2+-loaded NPT possessed better antibacterial activity than ECO/zein nanoparticles. Finally, the test of application in fruit juice indicated that ECO/Zn2+-loaded NPT had no significant effect on physico-chemical properties and exhibited potential application in juice preservation.

The Novel Nano-Formulation of the HDAC Inhibitor, Romidepsin, for the Treatment of Relapsed, Refractory Peripheral T-Cell Lymphoma

Background: The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of diseases often associated with a poor outcome. Since conventional chemotherapy fails to produce cure in the majority of patients, there is a lack of accepted standard of care for most PTCL subtypes. The PTCL appear to be a group of diseases characterized by gross epigenetic dysregulation with a unique vulnerability to epigenetic modulation. Recurring mutations in IDH2, TET2 and DNMT3A, which create a hypermethylator phenotype, coupled with mutations in genes that control histone acetylation such as EP300 and CREBBP, have been identified as recurrent in several subtypes of PTCL. Despite the approval of several drugs for patients with relapsed or refractory disease, the prognosis for patients with PTCL are dismally low. The approval of histone deacetylase inhibitors (HDACi) coupled with recent evidence suggesting that combinations of epigenetically targeted drugs induce clinically meaningful results has created a drug development strategy that offers an innovative approach to these complex diseases. The HDACi exhibit a lineage selective activity against the PTCL, with 4 HDACi (Belinostat, Romidepsin, Vorinostat and Chidamide) approved for Relapsed/Refractory (R/R) TCL patients around the world. Although Romidepsin was approved by the FDA for the treatment of cutaneous TCL and R/R PTCL, its indication in R/R PTCL was recently withdrawn due to the negative result of the Phase 4 commitment study. Objectives: We aim to develop a novel nano-encapsulated formulation of Romidepsin (Romi) with a superior safety and efficacy profile with a more convenient dosing schedule. Methods: Using a combinatorial strategy of solvent screening and polymer chemistries, we developed a first-in-class nano-romidepsin (NanoRomi). We utilized Dynamic Light Scattering (DLS), Cryo-EM to characterize the size and morphology of the nanoparticles and LC-MS-defined drug loading to "lock down” a nanoparticle formulation for in vitro testing. Cell viability, flow cytometry and western blotting (WB) assays were performed to determine the NanoRomi mediated cell death, apoptosis and histone acetylation in TCL cell lines. To determine maximum tolerated dose of the NanoRomi vs free Romi, in vivo single-dose toxicity study was performed. The clinical score and weight loss of the mice were considered endpoints. For pharmacokinetics study, mice were treated at the ½ MTD and plasma was isolated from blood collected at time points following a single treatment for mass spectrometry based quantification of drug levels. Results: We developed NanoRomi by nanoprecipitation or solvent displacement method using a specific Drug/Polymer/Surfactant ratio. Cryo-EM and DLS confirmed that NanoRomi had a poly-dispersity index between 0.16 to 0.27 and a z-average of 60-70 nm, indicating uniform size and homogenous particle distribution. At 60 hours, the TCL cell lines were consistently sensitive to NanoRomi (IC50: 0.7-1.9 nM), which was comparable to Romi (Fig 1A). Flow cytometry for cleaved PARP demonstrated that treatment with NanoRomi induced apoptosis similar to Romi. WB analysis showed increased acetylation of histone H3 and H4 in a time and concentration-dependent manner. In vivo single-dose toxicity assay showed a clear correlation between dose and weight loss and/or clinical score in both free Romi and NanoRomi treated groups. Mice reached humane endpoints at 8 mg/kg treatment for intraperitoneal route of administration for both the drugs. Preliminary PK analysis indicated that the t1/2 of Romi (plasma) is comparable between free Romi and NanoRomi treatments while the Cmax and AUC for NanoRomi is 3 to 4-fold higher compared to the free Romi. The plasma-concentration time courses of Romi after the intraperitoneal administration of the free Romi and NanoRomi showed that the drug reached maximum concentration after 6 hours and 3 hours for free Romi and NanoRomi, respectively (Fig 1B). Conclusions: These studies confirm that NanoRomi effectively targets tumor cells producing the same constellation of effects seen with free Romi. In addition, the in vivo studies suggest a likely superior safety and pharmacokinetic profile. NanoRomi may represent a valuable asset with unique properties that favorably distinguish it from free Romi. Ongoing studies are focused on the in vivo therapeutic efficacy, as we translate the development of this agent to Phase 1 studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Antimicrobial Activity of Azithromycin Encapsulated into PLGA NPs: A Potential Strategy to Overcome Efflux Resistance.

Antimicrobial resistance represents a public health problem with a major negative impact on health and socioeconomic development, and is one of the biggest threats in the modern era. This requires the discovery of new approaches to control microbial infections. Nanomedicine could be one of the promising strategies to improve the treatment of microbial infections. Polymer nanoparticles (PNPs) were reported to overcome the efflux-resistant mechanism toward chemotherapeutic agents. However, to the best of our knowledge, no studies were performed to explore their ability to overcome the efflux-resistant mechanism in bacteria. In the current study, azithromycin (AZI), a macrolide antibiotic, was encapsulated into a biocompatible polymer, poly (lactic-co-glycolic acid) (PLGA) using the nano-precipitation method. The effect of the drug to polymer ratio, surfactant, and pH of the aqueous medium on particle size and drug loading percentage (DL%) were investigated in order to maximize the DL% and control the size of NPs to be around 100 nm. The antibacterial activity of AZI-PLGA NPs was investigated against AZI-resistant bacteria; Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis (E. faecalis), where the efflux mechanism was demonstrated to be one of the resistant mechanisms. AZI-PLGA NPs were safer than free AZI, as revealed from the cytotoxicity test, and were able to overcome the efflux-resistant mechanism, as revealed by decreasing the MIC of AZI-PLGA NPs by four times than free AZI. The MIC value reduced from 256 to 64 µg/mL and from >1000 to 256 µg/mL for MRSA and E. faecalis, respectively. Therefore, encapsulation of AZI into PNPs was shown to be a promising strategy to overcome the efflux-resistant mechanism towards AZI and improve its antibacterial effect. However, future investigations are necessary to explore the effect (if any) of particle size, surface charge, and material composition of PNPs on antibacterial activity. Moreover, it is essential to ascertain the safety profiles of these PNPs, the possibility of their large-scale manufacture, and if this concept could be extended to other antibiotics.

Engineering and Validation of a Peptide-Stabilized Poly(lactic-co-glycolic) Acid Nanoparticle for Targeted Delivery of a Vascular Disruptive Agent in Cancer Therapy.

Developing a biocompatible and biodegradable nanoparticle (NP) carrier that integrates drug-loading capability, active targeting, and imaging modality is extremely challenging. Herein, we report an NP with a core of poly(lactic-co-glycolic) acid (PLGA) chemically modified with the drug combretastatin A4 (CA4), a vascular disrupting agent (VDA) in clinical development for ovarian cancer (OvCA) therapy. The NP is stabilized with a short arginine-glycine-aspartic acid-phenylalanine x3 (RGDFFF) peptide via self-assembly of the peptide on the PLGA surface. Importantly, the use of our RGDFFF coating replaces the commonly used polyethylene glycol (PEG) polymer that itself often induces an unwanted immunogenic response. In addition, the RGD motif of the peptide is well-known to preferentially bind to αvβ3 integrin that is implicated in tumor angiogenesis and is exploited as the NP's targeting component. The NP is enhanced with an optical imaging fluorophore label via chemical modification of the PLGA. The RGDFFF-CA4 NPs are synthesized using a nanoprecipitation method and are ∼75 ± 3.7 nm in diameter, where a peptide coating comprises a 2-3 nm outer layer. The NPs are serum stable for 72 h. In vitro studies using human umbilical cord vascular endothelial cells (HUVEC) confirmed the high uptake and biological activity of the RGDFFF-CA4 NP. NP uptake and viability reduction were demonstrated in OvCA cells grown in culture, and the NPs efficiently accumulated in tumors in a preclinical OvCA mouse model. The RGDFFF NP did not induce an inflammatory response when cultured with immune cells. Finally, the NP was efficiently taken up by patient-derived OvCA cells, suggesting a potential for future clinical applications.

Folate receptor-targeted PLGA-PEG nanoparticles for enhancing the activity of genistein in ovarian cancer

Genistein (GEN), a natural isoflavone possesses a wide range of pharmacological properties and nutraceutical applications. GEN has been studied for its anticancer activity against different types of cancers, but its use in clinical practice is limited due to its low water solubility, rapid metabolism and excretion, lack of cancer cell targeting and poor bioavailability. In the present study, we investigated folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles (PLGA-PEG-FA NPs) containing GEN for targeted delivery to ovarian cancer cells. PLGA-PEG and PLGA-PEG-FA polymer conjugates were synthesized and characterized. Nano-precipitation method was employed for the fabrication of NPs of PLGA, PLGA-PEG and PLGA-PEG-FA containing GEN. GEN containing PLGA-PEG and PLGA-PEG-FA NPs prepared were small (104.17 ± 1.61 and 125.41 ± 3.11 nm, respectively) and exhibited sustained release of GEN for around six days. Folate-decorated PLGA-PEG NPs showed increased cellular uptake in comparison to non-targeted PLGA-PEG NPs. The GEN containing PLGA-PEG-FA NPs showed superior anticancer activity than non-targeted PLGA and PLGA-PEG NPs in folate receptor-overexpressing ovarian cancer cell line, SKOV-3. The IC50 of GEN, GEN encapsulated NPs of PLGA, PLGA-PEG and PLGA-PEG-FA were 51.48, 26.70, 23.43 and 11.98 µg/ml, respectively. Folate-targeted PLGA nanoparticles could be developed for potential target-specific delivery of GEN in the treatment of ovarian cancer.

Chitosan Nanoparticles Loaded Poloxamer 407 Gel for Transungual Delivery of Terbinafine HCl.

The current study aimed to develop chitosan nanoparticles (CSNP) loaded poloxamer 407 (P407) gel formulation for transungual delivery of terbinafine HCl (TBN). TBN-CSNP were prepared by nanoprecipitation method and optimized by face-centered central composite design (FCCCD). Optimized TBN-CSNP formulation exhibited a spherical shape with hydrodynamic diameter; zeta potential and entrapment efficiency (EE) of 229 ± 5 nm; 37 ± 1.5 mV; and 75 ± 2% respectively. The solid state of TBN and its compatibility with formulation ingredients were confirmed through XRD and FTIR analysis respectively. TBN-CSNP loaded P407 gel exhibited pseudoplastic rheological behavior having a spreadability of 11 ± 2 g·cm/s. The washability study showed that 40 ± 2% of the gel was eroded after washing 12 times. Drug release from TBN-CSNP- and TBN-CSNP-loaded gel was 84 ± 5% and 57 ± 3%, respectively. The cumulative quantity of TBN permeated from TBN-CSNP-loaded P407 gel and TBN-loaded P407 gel was 25 ± 8 and 27 ± 4 µg/cm2, respectively. The nail uptake study showed that 3.6 ± 0.7 and 2.1 ± 0.3 µg of rhodamine was uptaken by the nail following 2 h topical application of TBN-CSNP loaded P407 gel and TBN loaded P407 gel, respectively. Hence, the developed CSNP-based P407 gel formulation can be a potential carrier for transungual delivery of TBN to topically treat onychomycosis.

Physicochemical characterisations of nanoencapsulated Eucalyptus globulus oil with gum Arabic and gum Arabic nanocapsule and their biocontrol effect on anthracnose disease of Syzygium malaccense Fruits

Nanoencapsulated E. globulus oil (NP and NC) and gum Arabic (NNP and NC) were prepared using nanoprecipitation (NP and NNP) and nanocapsule elaboration (NC and NNC) methods. Gas chromatography and gas chromatography-mass spectrometry (GC/GC-MS) were used to analyse the oil used in this study. Dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), loading capacity (LC), and encapsulation efficiency (EE) were used to characterise the nanoencapsulated oil. In addition to characterisation, an in-vitro kinetics study of the nanoencapsulated oil was carried out. Fungi were also isolated from rotten S. malaccense, and the pathogenicity of the fungi was determined. Furthermore, the nanoencapsulated oil was used to determine the in-vitro and in-vivo control of anthracnose in the fruits. The GC/GC-MS analysis revealed that eucalyptol (63.81%) was the most abundant constituent of the Eucalyptus oil. The DLS revealed that the average particle size of NP (219±280.94nm) increased compared to NNP (51.8768.44nm), while the average particle size of NC (516±165.21nm) decreased compared to NNC (548±73.73nm). Similarly, the average particle size as measured by TEM followed the same pattern as DLS, NP (7.52±3.54nm), NNP (4.43±1.18nm), NC (6.24±2.13nm), and NNC (8.89±1.54nm). Furthermore, there were additional FTIR peaks with the incorporation of the oil (NP) via the nanoprecipitation method; however, there was no peak with the incorporation of the oil (NC) via the nanocapsule elaboration method. The oil's (NP and NC) incorporation with the gum Arabic's (NNP and NP) LC, EE, and in-vitro release were all affected. Fungi isolated from rotten S. malaccense fruits revealed the presence of Rhizopus stolonifer, Colletotrichum gloeosporioides, and Aspergillus niger; C. gloeosporioides was also confirmed to be the cause of the rot in S. malaccense fruits. The nanoencapsulated oil's antifungal activities indicated that it could be used to control anthracnose disease in S. malaccense fruits.

Chemorepellent-Loaded Nanocarriers Promote Localized Interference of Escherichia coli Transport to Inhibit Biofilm Formation.

To mitigate antimicrobial resistance, we developed polymeric nanocarrier delivery of the chemorepellent signaling agent, nickel, to interfere with Escherichia coli transport to a surface, an incipient biofilm formation stage. The dynamics of nickel nanocarrier (Ni NC) chemorepellent release and induced chemorepellent response required to effectively modulate bacterial transport for biofilm prevention were characterized in this work. Ni NCs were fabricated with the established Flash NanoPrecipitation method. NC size was characterized with dynamic light scattering. Measured with a zincon monosodium salt colorimetric assay, NC nickel release was pH-dependent, with 62.5% of total encapsulated nickel released at pH 7 within 0-15 min, competitive with rapid E. coli transport to the surface. Confocal laser scanning microscopy of E. coli (GFP-expressing) biofilm growth dynamics on fluorescently labeled Ni NC coated glass coupled with a theoretical dynamical criterion probed the biofilm prevention outcomes of NC design. The Ni NC coating significantly reduced E. coli attachment compared to a soluble nickel coating and reduced E. coli biomass area by 61% compared to uncoated glass. A chemical-in-plug assay revealed Ni NCs induced a chemorepellent response in E. coli. A characteristic E. coli chemorepellent response was observed away from the Ni NC coated glass over 10 μm length scales effective to prevent incipient biofilm surface attachment. The dynamical criterion provided semiquantitative analysis of NC mechanisms to control biofilm and informed optimal chemorepellent release profiles to improve NC biofilm inhibition. This work is fundamental for dynamical informed design of biofilm-inhibiting chemorepellent-loaded NCs promising to mitigate the development of resistance and interfere with the transport of specific pathogens.

Imaging of Primary and Metastatic Tumors Treated with Radiotherapy-Directed Antigen-Capturing Nanoparticles, Reducing Metastasis-Seeding and Colonization, under PDL-1 Blockade

<h3>Purpose/Objective(s)</h3> We tested a treatment combining radiotherapy with antigen-capturing nanoparticles (AC-NPs; 112 ± 73 nm) containing digitoxin and anti-STAT-3 inhibitor (HJC0152) encapsulated in nanocapsules (545 ± 24 nm), which release their contents upon radiation exposure. We conducted two radiotherapy sessions: 1) treatment of primary tumor and metastases by immuno-radiotherapy and abscopal effect with PDL-1 blockade, respectively, and 2) reduction of new metastasis seeding and colonization by dissociation of circulating tumor cell (CTC)-clusters using digitoxin, and by impairing premetastatic niche (PMN) formation using a STAT-3 inhibitor (HJC0152), respectively. <h3>Materials/Methods</h3> In session one, nanocapsules were generated by mixing iopamiron, 400 mg of an anti-PD-L1 antibody (Ab), and 10 µg/mL HJC0152 with a 1.0 mL solution containing 4.0% alginate, 3.0% hyaluronate, and 1 µg/mL P-selectin. This mixture was sprayed into 0.5 mmol/l FeCl₂ supplemented with 1 µg/mL anti-VEGFR-1/2 Ab. In session two, 400 nM digitoxin was encapsulated in poly lactic-co-glycolic acid (PLGA) AC-NPs using the nanoprecipitation method. The particles were mixed with the above cocktail and sprayed into 0.5 mmol/L FeCl₂ with 1 µg/mL anti-P-selectin Ab. This yielded encapsulated PLGA AC-NPs containing digitoxin. In session one, 1 × 10¹⁰ nanocapsules were intravenously injected into BALB/c mice exhibiting a primary 4TI mammary carcinoma in the left hind leg and lung metastases. Tumor accumulation was monitored by computed tomography (CT). Subsequently, 10 or 20 Gy ⁶⁰Co γ-radiation was locally administered to primary tumors and lung metastasis. In session two, 1 × 10¹⁰ nanocapsules were injected i.v. and allowed to interact with P-selectin for 9 h; additionally, 10 or 20 Gy ⁶⁰Co γ-radiation was administered solely to the primary tumor. <h3>Results</h3> In session one, CT imaging of the accumulation of anti-VEGFR-1/2 nanocapsules around the primary and metastatic tumors improved their diagnosis. The nanocapsules released P-selectin, anti-PD-L1 Ab, and HJC0152 in response to the initial radiation dose. After session two, the nanocapsules accumulated around the primary tumor via a P-selectin Ag-Ab reaction. PLGA AC-NPs captured tumor-derived protein antigens released by the second radiation dose and intensified DC-mediated CD8⁺ T-cell priming. The primed CD8⁺ T-cells attacked PD-L1-suppressed primary and metastatic tumors. PLGA AC-NPs also released digitoxin, which dissociated CTC-clusters and reduced new metastasis seeding; the colonization of seeded tumor cells was subsequently inhibited through impaired PMN formation by HJC0152. Additionally, HJC0152 intensified DC-mediated CD8⁺ T-cell priming. These treatments significantly increased the antitumor effect (EF 1.7) and reduced metastasis by 88.8%. <h3>Conclusion</h3> Our CT-detectable nanocapsules will lead to better diagnosis and tumor treatment.

Molecular Cocrystals with Hydrogen-Bonded Polymeric Structures and Polarized Luminescence.

Crystalline materials with appealing luminescent properties are attractive materials for various optoelectronic applications. The in situ bicomponent reaction of 1,2-ethylenedisulfonic acid with 1,4-di(pyrid-2-yl)benzene, 1,4-di(pyrid-3-yl)benzene, or 1,4-di(pyrid-4-yl)benzene affords luminescent crystals with hydrogen-bonded polymeric structures. Variations in the positions of the pyridine nitrogen atoms lead to alternating polymeric structures with either a ladder- or zigzag-type of molecular arrangement. By using a nanoprecipitation method, microcrystals of these polymeric structures are prepared, showing polarized luminescence with a moderate degree of polarization.