Hollow Polymer Nanoparticles Research Articles

Facile Synthesis of Hollow Starch Nanoparticles for the Delivery of Piroxicam, a Poorly Water‐Soluble Drug

AbstractThis paper focuses on the development of hollow starch nanoparticles (HSNPs) as promising carriers for poorly soluble drugs. A new and efficient method is presented, based on an in situ gas‐foaming/salt‐leaching process within individual starch nanoparticles prepared by a solvent displacement technique. Characterization using dynamic light scattering, transmission electron microscopy, and nitrogen adsorption/desorption analysis confirmed the successful preparation of HSNPs. Solid dispersion systems with piroxicam (PRX) as a model drug were formulated to evaluate HSNPs’ potential as poorly water‐soluble drug carriers. Solid‐state properties, dissolution behavior and stability of PRX‐HSNPs solid dispersions were investigated. In vitro dissolution studies revealed that using hydrophilic HSNPs as carriers significantly improved the release of PRX. Solid‐state characterization showed that the main reason for the improved dissolution was the adsorption of PRX on the outer and inner surfaces of the HSNPs in an amorphous state. Stability studies demonstrated that the amorphous nature of loaded PRX remained unaffected even after 12 weeks of storage at 75 % relative humidity. Accordingly, the proposed HSNPs offer a promising alternative for the delivery of poorly water‐soluble drugs. In addition, the synthesis strategy demonstrated for HSNPs is easy, efficient and could be extended to the preparation of other hollow polymeric nanoparticles.

Poly (3-hexylthiophene) (P3HT) Crystalsomes: Tiling 1D Polymer Crystals on a Spherical Surface.

Polymer crystalsomes are a class of hollow crystalline polymer nanoparticles with shells formed by single crystals with broken translational symmetry. They have shown intriguing mechanical, thermal, and biomedical properties associated with spherical packing. Previously reported crystalsomes are formed by quasi-2D lamellae which can readily tile on a spherical surface. In this work, the formation of polymer crystalsomes formed by 1D polymer crystals is reported. Poly (3-hexylthiophene) (P3HT) is chosen as the model polymer because of its 1D growth habit. P3HT crystalsomes are successfully fabricated using a miniemulsion solution crystallization method, as confirmed by scanning electron microscopy and transmission electron microscopy. X-ray diffraction (XRD) and selected area electron diffraction experiments confirm that P3HT crystallized into a Form I crystal structure. XRD, differential scanning calorimetry and UV-Vis results reveal curvature-dependent structural, thermal and electro-optical properties.

Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

Tumor microenvironment-activated self-charge-generable metallosupramolecular polymer nanocapsules for photoacoustic imaging-guided targeted synergistic photothermal-chemotherapy

An integrated nanosystem of target, visualization, high circulation stability, and multi-therapy effects represents the leading direction of next generation anti-cancer strategy. Nevertheless, this normally requires elegant multi-component and hierarchical structure design of nanomaterials, or even a complicated post-treatment procedure, to combine different functions together. Herein, we show that hollow metallosupramolecular polymer nanoparticles (HMPNs) derived from a selective-etching approach based on Kirkendall effect have combined capabilities of (i) facile in-situ guest cargo encapsulation, (ii) reversible surface charge evolution, (iii) excellent photoacoustic property and (vi) highly synergistic photothermal-chemo therapeutic effect. Using DOX as a model drug, we can easily fabricate DOX-HMPNs because the etching process is accompanied with effective matter exchange between outer environment and inner particle, while significantly avoiding the premature drug leakage. Notably, synergistic effect between reversible phenolic hydroxyl ionization and dynamic catechol-FeIII coordination endows DOX-HMPNs with dramatic self-charge generation ability, thus achieving weakly acidic tumor microenvironment-activated reversible surface charge evolution. We have found that DOX-HMPNs with this self-charge generation feature can effectively achieve prolonged circulation and tumor recognition. Moreover, the cleavage of imine bond can induce the disassembly of hollow particles in strongly acidic lysosomes, and thus accelerate the release of DOX. This chemotherapy, in combination with the cascade-responsive behavior and photothermal/photoacoustic properties of HMPNs, makes our DOX-HMPNs exhibit synergistic antitumor efficiency and provide promising potential for cancer theranostic application.

A Versatile Strategy for Unimolecular Micelle-Derived Hollow Polymer Nanoparticles as General Nanoreactors.

We reported the synthesis of a well-defined hollow polymer nanoparticle derived from star-shaped unimolecular micelles. β-Cyclodextrin was first applied as an efficient macroinitiator to prepare a star-shaped PCL via ring-opening polymerization (ROP). Then, the star-shaped PCL was modified to be a macro-RAFT agent for photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization of S-Cl monomers. The prepared unimolecular micelles can be photocross-linked under UV irradiation after a simple nucleophilic substitution reaction, which made -Cl groups to be -N3 groups. After the selective removal of the PCL core, hollow polymer nanoparticles were achieved and exhibited to be a general nanoreactor strategy for the fabrication of nanocrystals with well-controlled architectures. Compared with unimolecular micelle templates, the nanocrystals prepared by hollow templates are absolutely pure as no polymer chains are embedded in the inorganic nanocrystals. In addition, by changing the concentration of the precursor, the structure of the nanocrystal can be changed from a normal spherical structure to a hollow structure.

Size-Controllable, Single-Step, and Scalable Synthesis of Hollow Polymer Nanoparticles.

Hollow polymer nanoparticles are of great importance in various industrial fields such as drug delivery vehicles in pharmaceutics, high thermal insulation materials for heat flow blocking and energy savings, and materials with unique optical properties. While the fabrication methods for hollow polymer nanoparticles have been studied and developed by numerous researchers, most synthesis methods require a rather complicated process, including a thorough core-washing step to formulate pores inside the particles. Single-step synthesis methods were developed to overcome this practical issue by utilizing the sacrificial solvent filling the pores temporarily and having it naturally evaporate without further process; however, such processes could not produce sub-200 nm diameter particles, which limit the application for high surface area applications. Herein, we have developed an innovative synthesis method that can overcome the particle size limitation by utilizing a sacrificial solvent for pore formation and a recondensation inhibitor. Pseudo-state Ostwald ripening was realized by selecting the sacrificial solvent with less affinity to the copolymer of hollow polymer particles, thus inhibiting the particle growth during polymerization. We have successfully obtained 120 nm diameter hollow PS-PMMA copolymer particles in large quantity via the single-step preparation of emulsion polymerization.

Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens.

BackgroundPoultry vaccine has limited choices of adjuvants and is facing severe threat of infectious diseases due to ineffective of widely used commercial vaccines. Thus, development of novel adjuvant that offers safe and effective immunity is of urgent need.Materials and MethodsThe present research engineers a novel chicken adjuvant with potent immune-potentiating capability by incorporating avian toll-like receptor 21 (TLR21) agonist CpG ODN 2007 with a poly(lactic-co-glycolic acid) (PLGA)-based hollow nanoparticle platform (CpG-NP), which subsequently assessed ex vivo and in vivo.ResultsCpG-NPs with an average diameter of 164 nm capable of sustained release of CpG for up to 96 hours were successfully prepared. With the ex vivo model of chicken bone marrow-derived dendritic cells (chBMDCs), CpG-NP was engulfed effectively and found to induce DC maturation, promoting dendrite formation and upregulation of CD40, CD80 and CCR7. In addition to enhanced expression of IL-1β, IL-6, IL-12 and IFN-γ, 53/84 immune-related genes were found to be stimulated in CpG-NP-treated chBMDCs, whereas only 39 of such genes were stimulated in free CpG-treated cells. These upregulated genes suggest immune skewing toward T helper cell 1 bias and evidence of improved mucosal immunity upon vaccination with the CpG-NP. The CpG-NP-treated chBMDCs showed protective effects to DF-1 cells against avian influenza virus H6N1 infection. Upon subsequent coupling with infectious bronchitis virus subunit antigen administration, chickens were immunostimulated to acquire higher humoral immune response and protective response against viral challenge.ConclustionThis work presents a novel hollow CpG-NP formulation, demonstrating effective and long-lasting immunostimulatory ability ex vivo and in vivo for chickens, as systemically compared to free CpG. This enhanced immune stimulation benefits from high stability and controlled release of internal component of nanoparticles that improve cellular delivery, lymphoid organ targeting and sustainable DC activation. CpG-NP has broad application potential in antiviral and vaccine development.

Effects of Lignin-Based Hollow Nanoparticle Structure on the Loading and Release Behavior of Doxorubicin.

Because of their exceptional absorption capacity, biodegradability, and nontoxicity, nanomaterials fabricated from renewable natural resources have recently become an increasingly important research area. However, the mechanism of drug encapsulation by lignin nanoparticles and the role of nanoparticle structure on the stability and loading performance still remain unknown. Herein, lignin hollow nanoparticles (LHNPs) were prepared and applied as promising vehicles for the antineoplastic antibiotic drug doxorubicin hydrochloride (DOX). The hydrogen bonding and π−π interactions contributed to the encapsulation of hydrophilic DOX by LHNPs with hydrophobic cavities. The encapsulation of DOX was enhanced by the pore volume and surface area. In addition, the nanoparticles contributed to the cellular uptake and the accumulation of the drug within HeLa cells. This work provides a scientific basis for future studies on the selective entrapment properties of hollow polymer nanoparticles derived from biomass material as vehicles for overcoming pharmacokinetic limitations.

Reactive Gelation Synthesis of Monodisperse Polymeric Capsules Using Droplet‐Based Microfluidics

AbstractA novel methodology, combining reactive gelation and droplet‐based microfluidics, is described for the synthesis of rigid, porous, and hollow polymeric nanoparticles (NPs). The precursors of such capsules are microfluidically generated latex droplets, with diameters tunable between 20 and 100 µm. The conversion of latex droplets to polymeric capsules involves two steps, namely self‐migration and gelation of the NPs toward the oil–water interface to form a solid‐like shell, and then postpolymerization to covalently fix the shell structure. The hollow structure of the capsules results from the interaction between negatively charged NPs inside the droplet and positive charges present on fluorosurfactant at the droplet interface. Significantly, the porosity and average pore size in the capsule shell can be controlled through variation of the initial NP concentration in the droplet. Based on the analysis of diffusion of fluorescent molecules of known size, it is shown that penetration of molecules into the internal volume of the capsules increases as the initial NP concentration in the droplet decreases, thus the porosity of the formed shell increases. This novel synthetic methodology defines a powerful tool in the generation of hollow capsules of controlled size and morphology, and has significant application in material sciences.

Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus.

The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS‐CoV) calls for the development of novel vaccine technology that offers safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus‐like fashion. STING agonists are first encapsulated into capsid‐like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH‐responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen‐specific T cell responses in mice immunized with a MERS‐CoV nanoparticle vaccine candidate. Using a MERS‐CoV‐permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle‐based MERS‐CoV vaccine are protected against a lethal challenge of MERS‐CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.

Rapid removal of copper ions from aqueous media by hollow polymer nanoparticles

High-performance adsorbents are central to the effective removal of heavy metal ions from aqueous media by adsorption. In this study, novel carboxylate-functionalized hollow polymer nanoparticles (HPPs-COO-) were used to remove Cu(II) from aqueous media. The FT-IR, XPS and EDS results demonstrated that the complexation of Cu(II) with the carboxylate group was in a bidentate bridging form. The optimal pH for adsorption was 5.0, and the adsorption behavior could be described by the Langmuir isotherm and pseudo-second-order kinetics model. HPPs-COO- had a comparable adsorption capacity (145.14 mg/g) with other reported polymeric adsorbents. In addition, the adsorption equilibrium of Cu(II) onto HPPs-COO- could be achieved within 1 min. The superfast adsorption rate allowed the quick removal of Cu (II) from the wastewater, and definitely reduced the operating cost. The application of HPPs-COO- in the treatment of real wastewater showed that not only the main contaminant Cu(II), but other toxic heavy metal ions Ni(II) and Pb(II) in the wastewater could be effectively removed. Additionally, HPPs-COO- exhibited a good reusability in the treatment of the wastewater. The above results revealed that HPPs-COO- had a bright prospect in the application of the wastewater treatment.

Faceted polymersomes: a sphere-to-polyhedron shape transformation.

The creation of "soft" deformable hollow polymeric nanoparticles with complex non-spherical shapes via block copolymer self-assembly remains a challenge. In this work, we show that a perylene-bearing block copolymer can self-assemble into polymeric membrane sacs (polymersomes) that not only possess uncommonly faceted polyhedral shapes but are also intrinsically fluorescent. Here, we further reveal for the first time an experimental visualization of the entire polymersome faceting process. We uncover how our polymersomes facet through a sphere-to-polyhedron shape transformation pathway that is driven by perylene aggregation confined within a topologically spherical polymersome shell. Finally, we illustrate the importance in understanding this shape transformation process by demonstrating our ability to controllably isolate different intermediate polymersome morphologies. The findings presented herein should provide opportunities for those who utilize non-spherical polymersomes for drug delivery, nanoreactor or templating applications, and those who are interested in the fundamental aspects of polymersome self-assembly.

Hollow chitosan nanocomposite as drug carrier system for controlled delivery of ramipril

Hollow biodegradable polymer nanoparticles as drug carrier possess effective low density and higher surface area. Chitosan hollow nanospheres were prepared using poly-D,L-lactide-co-glycolide as template by single emulsion method. The DLS studies showed increase in size from 125 nm to 186 nm for the formation of core@shell structure. The BET surface area increased from 62 m2 g−1 for chitosan@poly-D,L-lactide-co-glycolide to 111 m2 g−1 for hollow chitosan nanospheres. TEM analyses indicated core@shell, chitosan@poly-D,L-lactide-co-glycolide and the hollow morphology of the chitosan nanospheres. Ramipril in acetone (1.5 mg/mL, 3 mg/mL and 5 mg/mL) was physically adsorbed onto hollow chitosan nanospheres and the amount of adsorbed ramipril was determined by HPLC. Higher entrapment efficiency (91%) with 96% of the drug content was observed for the sample with 5 mg/mL of the drug. The in-vitro release of ramipril of 86% and 73% was achieved in acetate (pH-3.3) and phosphate (pH-6.3) buffers respectively while only 48% of ramipril in Tris buffer (pH-8.0) medium. Korsemeyer-Peppas model of drug release indicated the release of ramipril being swelling controlled.

Polymer donors of nitric oxide for enhanced accumulation of anticancer agents in solid tumors

This work reported the design, preparation and characterization of functional hollow polymer nanoparticles with S-nitrosothiol (SNO) as scaffolds for nitric oxide (NO) release in PBS buffer and bovine serum. The thiolated hollow polymer nanoparticles were prepared by distillation precipitation polymerization of ethyleneglycol dimethacrylate (EGDMA) and 2-hydroxyethyl methacrylate (HEMA) in presence of 3-(methacryloxy)propyltrimethoxysilane (MPS)-modified silica as seeds and the selective removal of silica core in hydrofluoric acid (HF) aqueous solution together with the subsequent surface esterification of hydroxyl groups with acryloyl chloride to introduce high density of vinyl groups and further Michael addition of carbon–carbon double bonds with hydrosulfide (HS−) anions. S-Nitrosothiol (SNO) functionalized hollow polymer nanoparticles were prepared via nitrosation of the surface thiol groups with acidified nitrite. The releasing characters of SNO-functionalized hollow polymer nanoparticles as NO scaffolds with capacity of 1.55 μmol/mg were investigated in different media, including PBS buffer exposure to trace copper cations and in real bovine serum.

Hollow double-layered polymer nanoparticles with S-nitrosothiols for tumor targeted therapy.

Tumor targeted hollow double-layered polymer nanoparticles (HDPNs) with S-nitrosothiols for nitric oxide (NO)-release as chemotherapy were described. Via a two-stage distillation precipitation co-polymerization, simple post-treatment and S-nitrosothiol modification, the S-nitroso HDPNs showed pH and glucose dual responsiveness. This would benefit accurate binding with the sialic acid over-expressed cancer cells, providing prerequisites for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO release. Confocal microscopy and cytotoxicity assay with normal versus tumor cells demonstrated in vitro recognition, intracellular delivery ability and tumor cell targeting cytotoxicity. Especially worth mentioning, the inevitable small amount of NO leakage in the transmission would take part in normal physiological activities and not cause serious side effects, providing a possible solution to avoid the intolerable side effects of traditional chemotherapy treatments for cancer.

Novel hollow and yolk-shell structured periodic mesoporous polymer nanoparticles.

The pioneered construction of novel monodisperse hollow and yolk-shell structured periodic mesoporous polymer nanoparticles was reported by the development of an efficient reactive interface-guided co-assembly approach.

A facile method of synthesizing size-controlled hollow cyanoacrylate nanoparticles for transparent superhydrophobic/oleophobic surfaces

A novel method to synthesize size-controllable hollow polymeric nanoparticles is reported. The synthesis process completes in a moment with tunable particle diameters. Coated surfaces show superhydrophobicity/oleophobicity with high transparency.

Hollow polymer nanoparticles with S-nitrosothiols as scaffolds for nitric oxide release

This work reported the design, preparation and characterization of functional hollow polymer nanoparticles with S-nitrosothiol (SNO) as scaffolds for nitric oxide (NO) release in PBS buffer and bovine serum. The thiolated hollow polymer nanoparticles were prepared by distillation precipitation polymerization of ethyleneglycol dimethacrylate (EGDMA) and 2-hydroxyethyl methacrylate (HEMA) in presence of 3-(methacryloxy)propyltrimethoxysilane (MPS)-modified silica as seeds and the selective removal of silica core in hydrofluoric acid (HF) aqueous solution together with the subsequent surface esterification of hydroxyl groups with acryloyl chloride to introduce high density of vinyl groups and further Michael addition of carbon–carbon double bonds with hydrosulfide (HS−) anions. S-Nitrosothiol (SNO) functionalized hollow polymer nanoparticles were prepared via nitrosation of the surface thiol groups with acidified nitrite. The releasing characters of SNO-functionalized hollow polymer nanoparticles as NO scaffolds with capacity of 1.55μmol/mg were investigated in different media, including PBS buffer exposure to trace copper cations and in real bovine serum.

Robust Route to Unimolecular Core–Shell and Hollow Polymer Nanoparticles

Unimolecular core–shell and hollow polymer nanoparticles with well-defined dimensions were crafted using spherical core–shell star-like diblock copolymers as templates. Monodisperse and structurally stable star-like diblock copolymers composed of inner degradable core blocks and outer photo-cross-linkable shell blocks were synthesized via a combination of two living polymerization techniques, namely, coordination–insertion ring opening polymerization (ROP) followed by reversible addition–fragmentation chain-transfer polymerization (RAFT). Subsequently, uniform unimolecular core–shell nanoparticles were successfully produced by photo-cross-linking the shell blocks of star-like diblock copolymers. The core diameter and shell thickness of nanoparticles are determined by molecular weights of inner core block and outer shell block, respectively, thereby rendering nanoparticles with tunable structural characteristics. The cross-linking density of nanoparticles can be readily controlled by varying the exposure time of star-like diblock copolymer templates to UV illumination. The selective degradation of inner core blocks yielded hollow polymer nanoparticles which retained structural integrity. The dye encapsulation and release studies revealed that unimolecular core–shell nanoparticles may be exploited as a new class of nanocarriers and promising drug nanovehicles.

Inverse Miniemulsion Periphery RAFT Polymerization: A Convenient Route to Hollow Polymeric Nanoparticles with an Aqueous Core

The recently developed [Chem. Commun. 2012, 48, 11103−11105] inverse miniemulsion periphery RAFT polymerization (IMEPP) approach to prepare hollow polymeric nanoparticles (∼200 nm) with an aqueous core has been explored in detail. The method is based on an amphiphilic macroRAFT agent acting as stabilizer of water droplets in an organic continuous phase while also mediating cross-linking chain growth in a controlled/living manner on the outer periphery of the droplets. The macroRAFT agent comprised a hydrophilic block of poly(N-(2-hydroxypropyl)methacrylamide) and a hydrophobic block of either polystyrene or poly(methyl methacrylate), and the cross-linked shell was formed on polymerization of styrene/divinylbenzene or methyl methacrylate/ethylene glycol dimethacrylate, respectively. The effects of various reaction parameters on the resulting hollow nanoparticles have been systematically investigated, and it has been demonstrated that the shell thickness can be tuned based on initial stoichiometry and monom...