Copolymer Nanoparticles Research Articles

Fabrication of a novel hybrid poly(amide-co-arylate)/MOF thin film membranes for organic solvent nanofiltration: optimization of membrane separation performance

Introducing a high separation performance membrane is one of the most essential requirements of an efficient polymeric membrane-based technology. In this regard, we employed different weight ratio of cardo-structured 9,9-bis(4-hydroxyphenyl)fluorene monomer (BHPF) to fabricate the novel polyacrylonitrile (PAN)-based poly(amide- co -arylate) thin film composite membranes through interfacial polymerization for use in organic solvent nanofiltration (OSN) field. In addition, the prepared poly(amide- co -arylate) thin films were filled with different content of porous metal organic framework (MOF) nanoparticles in order to attain high permeable polymeric membranes. Besides, the organically modified MOF nanoparticles and poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide-co-poly(2-hydroxyethyl methacrylate) (PMSA- co -PHEMA) copolymer nanoparticles containing zwitterionic groups were synthesized for further investigation. It was found that the designed poly(amide- co -arylate) thin film composite membrane fabricated by equal ratios of m -phenylenediamine (MPD) and BHPF monomers showed the highest tetrahydrofuran (THF) flux value compared with other thin film composite (TFC) membranes. Moreover, incorporating 0.003 wt% of MOF nanoparticles within this poly(amide- co -acrylate) thin film led to a good retention up to 90, 88 and 98% for bromophenol blue (BPB), acid blue 7 (ACB) and methyl green (MG) dyes, respectively. Furthermore, this thin film nanocomposite (TFN) membrane displayed an acceptable pure THF flux as high as 2 Lm-2h-1bar-1 at 10 bar. Also, evaluating long-term stability application of this TFN membranes demonstrated a slight reduction in THF flux, indicating that this membrane is highly efficient for use in the OSN field. • The novel hybrid PAN-based poly(amide- co -arylate)/MOF thin film membranes were fabricated. • The modified MOF nanoparticles and PMSA- co -PHEMA copolymer nanoparticles comprising zwitterionic groups were synthesized. • The TFN membrane containing 0.003 wt% MOF exhibited the pure THF flux around 2 Lm-2h-1bar-1. • The high rejection value around 90, 88 and 98% was observed for BPB, ACB and MG dyes, respectively.

Abstract P059: Exploiting mutant PPM1D-induced metabolic defects with nanoparticle-encapsulated NAMPT inhibitors

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a leading cause of death in pediatric cancer, with an abysmal <1% 5-year survival rate due to lack of effective treatment options. A significant effort is needed to understand the genetic landscape of this disease to develop novel therapeutic strategies and modalities. Recently, the Bindra laboratory found that a truncation mutation in the gene PPM1D, found in ~30% of DIPG cases, causes global epigenetic alterations that lead to therapeutic vulnerabilities. They found that mutant PPM1D activity results in loss of the NAD+ biogenesis protein NAPRT that can be therapeutically targeted by inhibitors of another protein in the NAD+ biogenesis pathway NAMPT (NAMPTi), providing a viable therapeutic strategy for these cancers. Some NAMPTis have been FDA-approved for clinical usage, but present with systemic and retinal toxicity. Moreover, while there are few NAMPTis that can pass the blood brain barrier through systemic delivery, studies show diminished concentrations at the target site. Together, current studies show that the use of NAMPTis for precision targeting of CNS cancers such as DIPG with mutant PPM1D status is a promising therapeutic strategy, but impractical given the limitations of these drugs. However, recent developments in drug delivery systems offer a chance to overcome these issues. Tools such as nanoparticle (NP) drug delivery and unique injection set-ups such as convection-enhanced delivery (CED) allow for drugs such as NAMPTis to be reconsidered for clinical usage. To circumvent the challenges presented by these drugs, we have developed and characterized nanoparticles that encapsulate NAMPTis (NAMPTi-NP) and use CED for sustained intratumoral delivery. Thus far, we have fabricated and optimized PLA-PEG copolymeric nanoparticles capable of encapsulating the NAMPTi, GMX-1778. We characterized these nanoparticles based on (1) hydrodynamic diameter, (2) zeta potential, and (3) stability within an artificial cerebrospinal fluid solution. We have performed both in vitro and in vivo assays to determine the functionality of the NAMPTi-NPs through (1) cellular uptake studies via immunofluorescence, (2) functional analysis via NAD+ quantification, (3) short- and long-term cell viability assays to determine sensitivity to the NAMPTi-NP, and (4) in vivo biodistribution studies to assess sustained retention of NAMPTi-NP with CED intracranial injections. We find that NAMPTi-NPs have immediate and sustained cellular uptake, loss of NAD+ post-treatment indicating effective targeting, and enhanced sensitivity in long-term viability studies in mutant PPM1D models. Lastly, these NAMPTi-NP display prolonged retention in brain tissue compared to free drug injection over time. With further in vivo validation, this NP-based strategy will be a powerful tool for targeting mutant PPM1D DIPG and other cancers. Citation Format: Matthew A. Murray, Yazhe Wang, Ranjini Sundaram, Jason Beckta, Mark Saltzman, Ranjit Bindra. Exploiting mutant PPM1D-induced metabolic defects with nanoparticle-encapsulated NAMPT inhibitors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P059.

A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity. To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named “PLGA-PEG-poly(I:C)” (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4+ T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1, IgG2c in serum, and sIgA in lung washings. Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses.

Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.

The methacrylic acid–ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/− 9.14 nm with a PDI of 0.37085 +/− 0.014 and a zeta potential of −13.7125 +/− 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

Synthesis of High-Performance Aqueous Fluorescent Nanodispersions for Textile Printing-A Study of Influence of Moles Ratio on Fastness Properties.

Aqueous fluorescent dispersions containing dyed acrylic-based copolymer nanoparticles possess significant credentials concerning green technology as compared to those prepared with the conventional vinyl-based monomers in textile and garment sectors; however, their essential textile fastness properties are yet to achieve. In the present work, a series of acrylic nanodispersions were synthesized by varying the moles ratio of benzyl methacrylate (BZMA), methyl methacrylate (MMA), and 2-hydroxypropyl methacrylate (HPMA) monomers. This was done to study their effect on dye aggregation and dyed polymer particles agglomeration. FT-IR spectral analysis showed the formation of polymer structures, while Malvern Analyzer, Transmission Electron Microscopy, and Scanning Electron Microscopy analysis suggested that the particles are spherical in shape and their size is less than 200 nm. The obtained nanodispersions were later applied on cotton fabrics for the evaluation of wash fastness and colour migration. Premier color scan spectrophotometer and zeta potential measurement studies suggested that colour migration of printed cotton fabrics increased with an increasing agglomeration of particles and it was also observed to increase with the moles ratio of MMA and zeta potentials.

Horseradish peroxidase-triggered direct in situ fluorescent immunoassay platform for sensing cardiac troponin I and SARS-CoV-2 nucleocapsid protein in serum

Direct in situ fluorescent enzyme-linked immunosorbent assay (ELISA) is rarely investigated and reported. Herein, a direct in situ high-performance HRP-labeled fluorescent immunoassay platform was constructed. The platform was developed based on a rapid in situ fluorogenic reaction between Polyethyleneimine (PEI) and p-Phenylenediamine (PPD) analogues to generate fluorescent copolymer nanoparticles (FCNPs). The formation mechanism of FCNPs was found to be the oxidation of •OH radicals, which was further proved by nitrogen protection and scavenger of •OH radicals. Meantime, the fluorescence wavelength of FCNPs could be adjusted from 471 to 512 nm by introducing various substitution groups into the PPD structure. Using cardiac troponin I (cTnI) and SARS-CoV-2 nucleocapsid protein (N-protein) as the model antigens, the proposed fluorescent ELISA exhibited a wide dynamic range of 5–180 ng/mL and a low limit of detection (LOD) of 0.19 ng/mL for cTnI, and dynamic range of 0–120 ng/mL and a LOD of 0.33 ng/mL for SARS-CoV-2 N protein, respectively. Noteworthy, the proposed method was successful applied to evaluate the cTnI and SARS-CoV-2 N protein levels in serum with satisfied results. Therefore, the proposed platform paved ways for developing novel fluorescence-based HRP-labeled ELISA technologies and broadening biomarker related clinical diagnostics.

Effect of Solvophilic Chain Length in PISA Particles on Pickering Emulsion†

Main observation and conclusionThe morphology of polymeric nanoparticles prepared by polymerization‐induced self‐assembly (PISA) is depended on the degree of polymerization of the solvophilic and solvophobic blocks. Herein, a series of poly (N,N‐dimethylaminoethyl methacrylate)‐b‐poly (benzyl methacrylate) (PDMA‐b‐PBzMA) diblock copolymer spherical nanoparticles were synthesized via reversible addition‐fragmentation chain transfer (RAFT) mediated PISA. These diblock copolymer nanoparticles are with nearly the same hydrodynamic size and solvophobic chain length, but with different solvophilic chain length. We used these nanoparticles to stabilize the oil‐in‐water Pickering emulsion. We find that the stability of Pickering emulsion increases with the length of solvophilic chain of the nanoparticles. Moreover, the droplet size of the Pickering emulsion can be tailored by varying the oil/water ratio and concentration of nanoparticles.

Transformation of nanoparticles into compacts: A study on PLGA and celecoxib nanoparticles

Oral delivery of nanoparticles possesses many advantages for delivery of active pharmaceutical ingredients (APIs) to the gastrointestinal tract. However, the poor physical stability of nanoparticles in liquid state is often a challenge. Removing water from the nanosuspensions and transforming the nanoparticles into solid particulate matter in the form of, e.g., tablets could be a potential approach to increase the stability of nanoparticles. The aim of this study was to transform nanoparticles into compacts and to investigate the redispersion of nanoparticles from compacts as well as the dissolution behavior of these compacts. DL-lactide-co-glycolide copolymer (PLGA) nanoparticles and celecoxib (CLX) nanoparticles were used as two model nanoparticle systems and fabricated into nano-embedded microparticles (NEMs) and subsequently compressed into compacts. The compacts were evaluated with respect to the redispersibility of the nanoparticles, as well as the dissolution characteristics of CLX. The results showed that the NEMs could be readily compressed into compacts with sufficient mechanical strength. The size of the redispersed PLGA nanoparticles from the compacts using 2-hydroxypropyl-β-cyclodextrin (HPβCD) as stabilizer was comparable to the original nanoparticles. In contrast, the redispersibility of CLX nanoparticles from the compacts was not as effective as for the PLGA nanoparticles evidenced by a significant increase in the size and polydispersity index (PDI) of the redispersed nanoparticles. Nonetheless, an obvious enhancement in dissolution rate of CLX was observed from the compacts with CLX nanoparticles. It is concluded that transforming polymeric nanoparticles into compacts via NEMs provides stabilization and allows redispersion into original nanoparticles. Despite the reduced redispersibility, compacts loaded with nanoparticles exhibited improved dissolution rate compared with the crystalline drug. Loading of nanoparticles into compacts is a promising approach to overcome the poor stability of nanoparticle within oral drug delivery of nanoparticles.

How a family of nanostructured amphiphilic block copolymers synthesized by RAFT-PISA take advantage of thiol groups to direct the in situ assembly of high luminescent CuNCs within their thermo-responsive core

• Multithiolated block copolymer nanoparticles (P-NPs) were synthesized by RAFT-PISA. • Monodisperse P-NPs with tunable size are formed under uncontrolled RAFT polymerization. • P-NPs with thermo-responsive core and hydrophilic shell exhibit high water stability. • Thiolated P-NPs serve as template for in situ assembly of luminescent CuNCs in water. • Fluorescent nanohybrids exhibit pH/thermo-response, photostability and oxidation resistance. The development of fluorescent water stable copper nanoclusters (CuNCs) deserves the scientific interest due to their outstanding properties and low-cost. These fluorescent CuNCs can be synthesized using natural or synthetic polymers with thiol groups. Herein, for the first time, we propose the use of novel amphiphilic block copolymer nano-objects, synthesized by polymerization induced self-assembly (PISA) via reversible-addition fragmentation chain transfer (RAFT), as templates for the synthesis and water stabilization of CuNCs. The polymeric NPs provide water-stability due to the poly(hydroxyethyl acrylate) corona and the thermos-responsive core, based on 2-(2-methoxyethoxy) ethyl methacrylate (MEO 2 MA) and 2-(acetylthio) ethyl methacrylate (AcSEMA) decorated with protected thiol groups, drive the “ in situ ” reduction of copper ions into copper nanocrystals and their assembling in high luminescent nanohybrids in water. In order to optimize the fluorescence properties a methodical study was carried out varying polymers composition and architecture, thiol content and nanoparticle size. All the polymeric nanoparticles synthesized by PISA and decorated with thiol groups induce the formation of luminescent CuNCs in their hydrophobic core. The sizes of the hydrophilic/hydrophobic block, as well as, thiol content are key factors in the emission properties of the CuNC nanohybrids that offer high colloidal stability in water, pH- and thermo-response, significance photostability and strong resistance to oxidation.

Novel nanofiltration membrane prepared by amphiphilic random copolymer nanoparticles packing for high-efficiency biomolecules separation

Nanofiltration (NF) as a promising candidate is widely used in charge-based separation of ampholytic biomolecules. Construction of strongly charged permeation channel of NF membrane is one of the key factors for this process. In this work, random amphiphilic copolymer (RACP) nanoparticles were first packed to prepare nanoscale permeation channel. The RACP emulsion was firstly prepared by soap-free emulsion polymerization between [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride (DMC) and methyl methacrylate (MMA), and then directly depositing onto porous substrate to form nanochannel selective layer of NF membrane. The optimal NF membrane shows a relatively large pore structure (i.e., cut-off pore size is 1.43 nm) and high pure water permeance (PWP) of 13.3 L·m−2·h−1·bar−1. Moreover, it shows a desirable rejection of basic amino acids and biopeptides (i.e., ∼95%) and allows neutral or acidic ones with similar molecule weight to permeate through. This work provides an innovative and facile method directly from RACP emulsion to construct NF membrane via nanoparticle packing, which greatly simplifies the preparation procedure for NF membrane. In addition, this novel NF membrane also demonstrates great potential in charge-based separation of biomolecules.

In Vivo Delivery of siRNAs Targeting EGFR and BRD4 Expression by Peptide-Modified Redox Responsive PEG-PEI Nanoparticles for the Treatment of Triple-Negative Breast Cancer.

The study aims to investigate the in vivo distribution, antitumor effect, and safety of cell membrane-penetrating peptide-modified disulfide bond copolymer nanoparticles loaded with small-interfering RNA (siRNA) targeting epidermal growth factor receptor (EGFR) and bromodomain-containing protein 4 (BRD4) in triple-negative breast cancer (TNBC). Polyethylene glycol disulfide bond-linked polyethylenimine (PEG-SS-PEI) was modified with peptides GALA and CREKA and used as vectors to prepare siRNA nanoparticles. The GALA- and CREKA-modified PEG-SS-PEI nanoparticles (GC-NPs) were prepared by mixing siEGFR and siBRD4 (1:1) with GALA-PEG-SS-PEI and CREKA-PEG-SS-PEI (1:1) in an aqueous solution at an N/P ratio of 30:1. Nanoparticles loaded with scrambled siRNA were prepared with the same method. The gene silencing effect on EGFR and BRD4 in vitro was evaluated by Western blotting analysis. TNBC xenograft models were established by subcutaneous injection of MDA-MB-231 cells into female nude mice. At 1, 3, 6, 12, and 24 h after administration of five formulations of Cy5-siRNA (133 μg/10 g) via the tail vein, the mice were observed and imaged for a biodistribution study using an in vivo imaging system. In the pharmacodynamics experiment, tumor-bearing mice were treated with respective siRNA preparations at a dose of 133 μg/10 g for 18 days, and the body weight and tumor size were recorded every other day. The protein expression levels of EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt, BRD4, and c-Myc were determined using Western blotting analysis. Hematological and serum biochemical parameters, organ indices, and HE staining results for the heart, liver, spleen, lung, and kidney were analyzed to evaluate the safety of the nanoparticles. GC-NPs loaded with siEGFR and siBRD4 significantly inhibited the expression of EGFR and BRD4 in vitro. The strongest fluorescence signals were observed in the GC-NP group, especially in tumors, indicating the excellent tumor-targeted delivery of GC-NPs we constructed. Tumor growth was significantly inhibited in the GC-NP-treated group, and the expression of EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt, BRD4, and c-Myc in the tumors decreased by 71%, 68%, 61%, 68%, 48%, 58%, 59%, and 74% compared to the control group, respectively. There was no significant change in hematological parameters, biochemical indices, or tissue morphology in GC-NP-treated mice. SiRNA cotargeting EGFR and BRD4 delivered by GALA- and CREKA-modified PEG-SS-PEI had favorable antitumor effects in vivo toward TNBC with tumor-targeting efficacy and good biocompatibility.

Discovery and Validation of a Compound to Target Ewing's Sarcoma.

Ewing’s sarcoma, characterized by pathognomonic t (11; 22) (q24; q12) and related chromosomal ETS family translocations, is a rare aggressive cancer of bone and soft tissue. Current protocols that include cytotoxic chemotherapeutic agents effectively treat localized disease; however, these aggressive therapies may result in treatment-related morbidities including second-site cancers in survivors. Moreover, the five-year survival rate in patients with relapsed, recurrent, or metastatic disease is less than 30%, despite intensive therapy with these cytotoxic agents. By using high-throughput phenotypic screening of small molecule libraries, we identified a previously uncharacterized compound (ML111) that inhibited in vitro proliferation of six established Ewing’s sarcoma cell lines with nanomolar potency. Proteomic studies show that ML111 treatment induced prometaphase arrest followed by rapid caspase-dependent apoptotic cell death in Ewing’s sarcoma cell lines. ML111, delivered via methoxypoly(ethylene glycol)-polycaprolactone copolymer nanoparticles, induced dose-dependent inhibition of Ewing’s sarcoma tumor growth in a murine xenograft model and invoked prometaphase arrest in vivo, consistent with in vitro data. These results suggest that ML111 represents a promising new drug lead for further preclinical studies and is a potential clinical development for the treatment of Ewing’s sarcoma.

Sunlight-induced photo-thermochromic smart window based spiropyran-functionalized copolymer for UV shielding and sunlight management

Energy efficient smart windows that automatically regulate the transmission of solar energy are one of the most promising ways to reduce energy consumption in buildings. However, current thermochromic smart windows based on Poly (N-isopropylacrylamide) (PNIPAm) only focus on the modulation of solar light through the phase transition of the material, while the contribution in UV modulation and energy storage are weak. Herein, we report a liquid thermo-responsive smart window Poly (NIPAm-co-SPMA7%) with UV resistance, light modulation and energy storage constructed by self-assembled amphiphilic block copolymer nanoparticles dispersed in water. Poly (NIPAm-co-SPMA7%) smart window has excellent thermal response solar modulation (Tlum, 20°C = 90.07% and ΔTsol = 87.59%), excellent energy absorption and storage capacity in aqueous solution, and strong absorption of UV light. In addition, this liquid smart window has a simple structure, good uniformity and scalability, which opens up a new way for energy-saving smart windows.

Hydroxypropyl methacrylamide-based copolymeric nanoparticles loaded with moxifloxacin as a mucoadhesive, cornea-penetrating nanomedicine eye drop with enhanced therapeutic benefits in bacterial keratitis

Bacterial keratitis (BK) is a leading cause of visual impairment. The fluoroquinolone antibiotic moxifloxacin (Mox), being highly water-soluble, suffers from poor corneal penetration leading to unsatisfactory therapeutic outcomes in BK. Here, we prepared Mox-loaded co-polymeric nanoparticles (NPs) by entrapping the drug in co-polymeric NPs constituted by the self-assembly of a water-soluble copolymer, poly(ethylene glycol)-b-p(hydroxypropyl) methacrylamide (mPH). The polymer (mPH) was prepared using a radical polymerization technique at different mPEG: HPMA ratios of 1:70/100/150. The polymer/nanoparticles were characterized by GPC, CAC, DLS, SEM, XRD, DSC, FTIR, % DL, % EE, and release studies. The ex vivo muco-adhesiveness and corneal permeation ability were judged using a texture analyzer and Franz Diffusion Cells. In vitro cellular uptake, cytotoxicity, and safety assessment were performed using HCE cells in monolayers, spheroids, and multilayers in transwells. The DOE-optimized colloidal solution of Mox-mPH NPs (1:150) displayed a particle size of ~116 nm, superior drug loading (8.3%), entrapment (83.2%), robust mucoadhesion ex vivo, and ocular retention in vivo (~6 h) (judged by in vivo image analysis). The non-irritant formulation, Mox-mPH NPs (1:150) (proven by HET-CAM test) exhibited intense antimicrobial activity against P. aeruginosa, S. pneumoniae, and S. aureus in vitro analyzed by live-dead cells assay, zone of inhibition studies, and by determining the minimum inhibitory and bactericidal concentrations. The polymeric nanoparticles, mPH (1:150), decreased the opacity and the bacterial load compared to the other treatment groups. The studies warrant the safe and effective topical application of the Mox-mPH NPs solution in bacterial keratitis.

Molecular simulation of molecular and surface properties of random copolymer nanoparticle

Random copolymer nanoparticles were studied by Monte Carlo simulation of coarse-grained models on the high coordination lattice. Molecular and surface properties of free-standing nanoparticle were characterized at fixed 50% co-monomer content as a function of the interaction strength between co-monomer units. Intramolecular interaction for all copolymer chains were treated by the Rotational Isomeric State (RIS) model of polyethylene (PE). To simulate the copolymer model, the non-bonded interactions for comonomer units were described by different parameter sets of the Lennard-Jones energy. When the co-monomer interaction was stronger, the bulk densities of nanoparticles were increased and the interfacial widths were narrower. Near the surface, end beads of copolymer chains were segregated and the bond orientation was preferably perpendicular to the surface. Molecular shape and molecular size of copolymer chains were slightly changed as a function of co-monomer interaction strength and most of which occurs close to the surface. For chain orientation, the largest principal axis tended to orient parallelly to the surface, and then changed toward randomly isotropic orientation for weaker co-monomer interaction. The intrachain energies were decreased at the surface region implying more trans conformation while the non-bonded energies were increased due to better monomer packing at the surface region. The change of system energetics was more apparent as a function of the co-monomer interaction.

Synthesis of ultra‐high molecular weight core cross‐linked star (CCS) polymer using high molecular weight spherical nanoparticles and arm‐first method

AbstractP (N,N‐Dimethylacrylamide) ‐b‐P (2‐methoxyethyl acrylate) (PDMA‐b‐PMEA) and Poly (poly (ethylene glycol) methyl ether methacrylate) ‐b‐P (2‐methoxyethyl acrylate) (PPEGMA‐b‐PMEA) di‐block copolymer nanoparticles are prepared by RAFT dispersion polymerization in water at 35°C. By changing the degree of polymerization (DP) of PMEA and the solid content of the reaction solution, only spherical nanoparticles are obtained. Using PDMA and PPEGMA as macromolecular chain transfer agents (Macro‐CTA), the actual DP of PMEA block can be up to 11,520 and 17,000, respectively, the size of the obtained spherical nanoparticles can be close to 600 nm, and the molecular weight of the block copolymer can reach 106. Such large spheres may serve as model sterically stabilized particles for analytical centrifugation studies. In the mixed solvent of ethanol and water (1:1, v/v), we synthesize ultra‐high molecular weight CCS polymer by the arm‐first method. Star polymer with such high molecular weight and small particle size can be used for emulsification.

Follicular-targeted delivery of spironolactone provided by polymeric nanoparticles

This study proposes developing a topical formulation based on poly-ε-caprolactone (PCL) or methacrylic acid/methyl methacrylate copolymer (EL100) nanoparticles to enable a safer and more effective therapy of alopecia and acne with spironolactone. The effect of the size of the nanoparticle on follicular-targeted drug delivery is also verified. Compatibility studies based on thermal analyses and complementary techniques showed a small interaction of the drug with excipients, which may not compromise the drug stability. PCL nanoparticles of 180.0 ± 1.6 and 126.8 ± 1.0 nm, and EL100 nanoparticles of 102.7 ± 7.1 nm were then prepared. All nanoparticles entrapped more than 75 % of spironolactone, were physically stable, and stabilized the drug for at least 90 days. They were also non-irritant according to HET-CAM tests. Drug release from the nanoparticles was reduced in aqueous buffer media but fast when in contact with oil. Finally, in vitro skin penetration experiments revealed the largest nanoparticles (of 180 nm) targeted drug delivery to the hair follicles 5-fold (p < 0.05) more than the control solution, 2.1-fold (p < 0.05) more than nanoparticles produced with the same polymer (PCL) but with smaller size (123 nm), and 4.9-fold (p < 0.05) more than the 102-nm E100 nanoparticles. In conclusion, follicular targeting can be adjusted according to nanoparticle size, and this work succeeded in obtaining polymeric nanoparticles adequate to enable topical treatment of acne and alopecia with spironolactone.

Expanding the Scope of Polymerization‐Induced Self‐Assembly: Recent Advances and New Horizons

Over the past decade or so, polymerization-induced self-assembly (PISA) has become a versatile method for rational preparation of concentrated block copolymer nanoparticles with a diverse set of morphologies. Much of the PISA literature has focused on the preparation of well-defined linear block copolymers by using linear macromolecular chain transfer agents (macro-CTAs) with high chain transfer constants. In this review, a recent process is highlighted from an unusual angle that has expanded the scope of PISA including i) synthesis of block copolymers with nonlinear architectures (e.g., star block copolymer, branched block copolymer) by PISA, ii) in situ synthesis of blends of polymers by PISA, and iii) utilization of macro-CTAs with low chain transfer constants in PISA. By highlighting these important examples, new insights into the research of PISA and future impact these methods will have on polymer and colloid synthesis are provided.

Ciprofloxacin-Releasing ROS-Sensitive Nanoparticles Composed of Poly(Ethylene Glycol)/Poly(D,L-lactide-co-glycolide) for Antibacterial Treatment.

Since urinary tract infections (UTIs) are closely associated with oxidative stress, we developed ROS-sensitive nanoparticles for ciprofloxacin (CIP) delivery for inhibition of UTI. Poly(D,L-lactide-co-glycolide) (PLGA)- selenocystamine (PLGA-selenocystamine) conjugates were attached to methoxypoly(ethylene glycol) (PEG) tetraacid (TA) (TA-PEG) conjugates to produce a copolymer (abbreviated as LGseseTAPEG). Selenocystamine linkages were introduced between PLGA and TA to endow reactive oxygen species (ROS) sensitivity to nanoparticles. CIP-incorporated nanoparticles of LGseseTAPEG copolymer were fabricated by W/O/W/W emulsion method. CIP-incorporated nanoparticles responded to H2O2 and then their morphologies were disintegrated by incubation with H2O2. Furthermore, particle size distribution of nanoparticles was changed from mono-modal distribution pattern to multi-modal distribution pattern by addition of H2O2. CIP release from nanoparticles of LGseseTAPEG copolymer was faster in the presence of H2O2 than in the absence of it. In antibacterial study using Escherichia coli (E. coli), free CIP and free CIP plus empty nanoparticles showed dose-dependent inhibitory effect against growth of bacteria while CIP-incorporated nanoparticles have less antibacterial activity compared to free CIP. These results were due to that CIP-incorporated nanoparticles have sustained release properties. When free CIP or CIP-incorporated nanoparticles were introduced into dialysis membrane to mimic in vivo situation, CIP-incorporated nanoparticles showed superior antibacterial activity compared to free CIP. At cell viability assay, nanoparticles of LGseseTAPEG copolymer have no acute cytotoxicity against L929 mouse fibroblast cells and CCD986sk human skin fibroblast cells. We suggest LGseseTAPEG nanoparticles are a promising candidate for CIP delivery.

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) with zinc oxide nanoparticles for food packaging

AbstractPoly(3‐hydroxybutyrate) (PHB) is a biodegradable biopolyester synthesized via bacterial fermentation from renewable resources that has received great attention over the last years for medicine and food packaging applications. However, it shows several shortcomings such as narrow processing window and a high crystallinity (&gt;50%), which leads to brittleness and low impact resistance. To solve these drawbacks, the hydroxybutyrate units can be copolymerized with other monomers like 3‐hydroxyhexanoate to yield poly(3‐hydroxybutyrate‐co‐3‐hydroxy‐hexanoate) (PHBHHx), a copolymer with higher ductility, improved impact strength, and lower melting point. However, PHBHHx displays lower crystallinity than PHB, hence reduced stiffness, and poorer barrier properties against moisture and gases, which is a disadvantage for its use as food packaging material. In this regard, (PHBHHx)‐based bionanocomposites incorporating 0.5, 1.0, 2.0, and 5.0 wt% zinc oxide (ZnO) nanoparticles were synthesized via solution casting technique. Their morphology, mechanical, thermal, barrier, and antibacterial properties were investigated via transmission electron microscopy, tensile and impact strength tests, thermogravimetric analysis, water vapor, and oxygen permeability measurements as well as antibacterial tests. In terms of gas permeability, the optimum performance was attained at 5.0 wt% ZnO loading, with reductions in the water vapor and oxygen permeability of 45 and 33%, respectively. Conversely, the impact strength decreased with increasing ZnO concentration, leading to 25% reduction for the highest ZnO loading tested. The bionanocomposite with 5.0 wt% ZnO is a promising alternative to synthetic plastics, with an optimal balance of toughness, barrier, and antibacterial properties to be used in packaging and disposable applications such as beverage and food containers.Practical applicationsThis study analyzes the morphology, thermal, mechanical, barrier, and antibacterial properties of biodegradable nanocomposites based on PHBHHx copolymer and ZnO nanoparticles. These safe and environmentally friendly nanomaterials can be used as a sustainable alternative to synthetic plastics for food and beverage containers.