Multifluorescently traceable nanoparticle by a single-wavelength excitation with color-related drug release performance

Monodisperse and nanometer-sized periodic mesoporous organosilicas co-doped with fluorescence resonance energy transfer cascades composed of triple fluorophores at various ratios were prepared. These nanoparticles exhibit multifluorescent emissions by a single-wavelength excitation and were designed for the application as multichannelly traceable drug carriers. Different from the hydrophilic framework of inorganic mesoporous silica and hydrophobic framework of mesoporous carbon, these multifluorescent nanoparticles have intrinsically different and finely tunable pore surface polarities governed by the type and amount of fluorophore inside the framework. When applied as drug carriers, they can achieve synchronous or asynchronous release of different drugs by simply choosing different colored nanoparticles. These colorful mesoporous composites with finely tunable color-related drug release performance provide a strong barcoding system for the potential applications of fluorescent nanoparticles in effective screening of drugs and therapeutic protocols for diseases.     

Supramolecular self-assembly and controllable drug release of thermosensitive hyperbranched multiarm copolymers

A novel temperature-responsive hyperbranched multiarm copolymer with a hydrophobic hyperbranched poly(3-ethyl-3-(hydroxymethyl)oxetane)(HBPO) core and thermosensitive poly(N-isopropylacrylamide)(PNIPAM) arms was synthesized via the atom transfer radical polymerization(ATRP) of NIPAM monomers from a hyperbranched HBPO macroinitiator.It was found that HBPO-star-PNIPAM self-assembled into multimolecular micelles(around 60 nm) in water at room temperature according to pyrene probe fluorescence spectrometry,1H N...     

Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer (H40-star-PLA-SS-PEG) based on Boltorn® H40 core, poly(l-lactide) (PLA) inner-shell, and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction. The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), gel permeation chromatography (GPC), differential scanning calorimeter (DSC), and thermal gravimetric analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm. Interestingly, these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol (DTT), most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds. As a hydrophobic anticancer model drug, doxorubicin (DOX) was encapsulated into these reductive unimolecular micelles. In vitro release studies revealed that under the reduction-stimulus, the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells. Methyl tetrazolium (MTT) assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX. All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.     

Encapsulation and controlled release of a hydrophobic drug using a novel nanoparticle-forming hyperbranched polyester

An amphiphilic, hyperbranched polymer suitable for use in controlled drug delivery is reported. This polymer was obtained by modification of the hyperbranched aliphatic polyester Boltorn H20 (H20) with succinic anhydride and then glycidyl methacrylate, and formed nanoparticles in aqueous solution. The critical association concentration was 7.4 x 10(-3) g . L(-1), as determined by fluorescence spectroscopy using pyrene as a molecular probe. A static/dynamic laser light scattering (LLS) study revealed that the average particle size was 39.4 nm with a low particle size distribution (PDI=0.04), and that each particle was composed of about 350 amphiphilic molecules. Daidzein, a hydrophobic traditional Chinese medicine, was encapsulated during particle formation and the release properties were determined. The optimal feeding concentration of daidzein to hyperbranched polyester was 4.9 x 10(-5) g . mL(-1) to 5.0 x 10(-3) g . mL(-1) with a loading efficiency of 76.1%. In the presence of the enzyme Lipase PS, the drug loaded nanoparticles degraded in a random one-by-one manner and released the drug over a few days. This system is therefore a novel controlled drug release system based on nanoparticles formed of hyperbranched polyester. Encapsulation of daidzein by hyperbranched polyester particles.     

Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems

Recent advancements in controlling the surface properties and particle morphology of the structurally defined mesoporous silica materials with high surface area (>700 m(2) g(-1)) and pore volume (>1 cm(3) g(-1)) have significantly enhanced their biocompatibility. Various methods have been developed for the functionalization of both the internal pore and exterior particle surfaces of these silicates with a tunable pore diameter ranging from 2 to 30 nm and a narrow pore size distribution. Herein, we review the recent research progress on the design of functional mesoporous silica materials for stimuli-responsive controlled release delivery of pharmaceutical drugs, genes, and other chemicals. Furthermore, the recent breakthroughs in utilizing these nanoscale porous materials as sensors for selective detections of various neurotransmitters and biological molecules are summarized.     

Polynuclear Cu(II) complexes with hyperbranched polyester carboxylates

Polydentate carboxylate platforms based on polyester polyol Boltorn H, containing from 8 to 14 carboxy groups in terminal positions were obtained. A method of synthesis of Cu(II) polynuclear complexes with polyester carboxylates Boltorn H with a degree of substitution of 65 and 90% was developed.     

Controlled release of DNA from photoresponsive hyperbranched polyglycerols with oligoamine shells

Two photo-responsive core/shell nanoparticles based on hyperbranched polyglycerol (hPG) are synthesized for controlled release of DNA. The shell is composed either of bis-(3-aminopropyl)methylamine (AMPA) or pentaethylenehexamine (PEHA) derivatives and is attached to the hPG core with a photo-responsive o-nitrobenzyl linker. Ethidium bromide displacement assay, gel electrophoresis, DLS, and ζ-potential measurements are performed with these nanoparticles. Photo-responsive changes within the carrier scaffold are investigated by irradiating the polymer solution with 350 nm monochromatic light. Fully covered APMA-shelled carriers are found to complex the DNA at an N/P ratio of 10 with an average size ranging from 54 to 78 nm depending on the degree of functionalization of the core.     

Synthesis and drug release properties of novel pH- and temperature-sensitive copolymers based on a hyperbranched polyether core

Multi-arm star amphiphilic hyperbranched copolymers with poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) shell and hyperbranched poly(3-ethyl-3-(hydroxymethyl)oxetane) (HBPO) core were synthesized by reversible addition?Cfragmentation chain transfer method. The hyperbranched copolymers were further modified by succinic anhydride (SUC) to obtain the novel pH- and thermosensitive hyperbranched copolymer HBPO-star-PDMAEMAs-SUC. The composition and morphology of synthesized copolymers were investigated by ¹H NMR, dynamic light scattering, and transmission electron microscopy. These copolymers exhibited phase transitions in response to pH and temperature. The pH-dependent release properties of the drug-loaded micelles were also investigated using indomethacin (IND) as a model drug. The IND-loaded micelles displayed a rapid drug release at an alkaline pH.     

Highly efficient intracellular drug delivery with a negatively charged hyperbranched polysulfonamine

Efficient intracellular translocation is achieved using an easily prepared hyperbranched polysulfonamine that remains negatively charged at physiological pH. Investigations on the cellular uptake mechanism and the subcellular distribution of PSA are reported. The in vitro cytotoxicity of PSA is found to be low. Using doxorubicin as a model drug, a PSA/drug complex is prepared by electrostatic interaction with a high drug payload that exhibits a controlled release in response to pH. Efficient intracellular drug delivery, strong growth inhibition of tumor cells, and low cytotoxicity to normal cells are observed. The results suggest a possible way to utilize anionic polymers for intracellular delivery of therapeutic moieties or drugs.     

Aggregation-induced emission-active antibacterial hydrogel with self-indicating ability for real-time monitoring of drug release process

Although antibacterial hydrogels are emerging as promising biomaterials for effective inhibition of bacterial infections, monitoring their dynamic release behaviors in a visual manner remains greatly challenging. Herein, non-conjugated luminescent polymers (NCLPs) with aggregation-induced emission (AIE) characteristics are used for the first time to develop a visualization strategy to monitor the release process of the drug-loaded hydrogel. The novel antimicrobial peptide polymers with intrinsic AIE effect, namely nanoengineered peptide-grafted hyperbranched polymers (NPGHPs), are encapsulated in an anionic polyelectrolyte to construct the AIE-active fluorescent polymeric hydrogel (NPGHPs/SA gel). Interestingly, the rigid environment mediated by hydrogen bonding and electrostatic interaction contributes to promoting the unconventional luminescence of fluorescent clusters. Moreover, the successive drug release process of NPGHPs/SA gel can be tracked in real time by using fluorescence microscopy. The hydrogel also has potent antibacterial activities against Gram-negative bacteria (E. coli, P. aeruginosa) and Gram-positive bacteria (S. aureus, B. subtilis). Overall, this work not only provides an advanced biomedical material with broad-spectrum antibacterial ability but also opens a facile avenue up for the investigation of drug release from gel systems.     

Supramolecular self-assembly of inclusion complexes of a multiarm hyperbranched polyether with cyclodextrins

A new class of crystalline inclusion complexes of a multiarm hyperbranched polyether combined with various cyclodextrins (CDs) was successfully prepared. Using self-condensing ring-opening polymerization, a kind of multiarm polyether with a hyperbranched poly(3-ethyl-3-oxetanemethanol) core and multiple linear poly(ethylene glycol) (PEG) arms was obtained. It has been found that this kind of hyperbranched polyether can be dissolved in water. Adding alpha-CDs to the multiarm hyperbranched polyether solution, molecular recognition results in the formation of crystalline inclusion complexes based on the noncovalent interactions between the linear PEG arms of the polyether particles and the alpha-CDs. These multiarm polyether inclusion complexes have been well characterized. Interestingly, quite different from inclusion complexes of CDs and linear polymeric guests, the complexes of the multiarm hyperbranched polyether with alpha-CDs show a novel lamellar morphology. The experimental results validate that the resultant lamellar crystals have a juxtaposed structure. In addition, the formation mechanism of these inclusion complexes of a multiarm polyether with alpha-CDs has also been well described. Besides the role of displacement of associated water molecules and the presence of hydrogen bonding between CDs in channel structure CD inclusion complexes, the noncovalent intermolecular forces between CDs and polymers also play an important role in the formation of complex architectures.     

Doubly hydrophilic multiarm hyperbranched polymers with acylhydrazone linkages as acid-sensitive drug carriers

A novel type of drug carrier capable of controlled drug release is proposed. It consists of an acid-sensitive doubly hydrophilic multiarm hyperbranched copolymer with a hyperbranched polyamidoamine core and many linear poly(ethylene glycol) arms. Using pH-sensitive acylhydrazone linkages, the polymer forms unimolecular micelles that can encapsulate hydrophobic drugs. Due to their amphiphilicity, the drug-loaded unimolecular micelles can self-assemble into multimolecular micelles that show acid-triggered intracellular delivery of the hydrophobic drugs.     

A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules

An MCM-41 type mesoporous silica nanosphere-based (MSN) controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide (CdS) nanocrystals as chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. We studied the stimuli-responsive release profiles of vancomycin- and adenosine triphosphate (ATP)-loaded MSN delivery systems by using disulfide bond-reducing molecules, such as dithiothreitol (DTT) and mercaptoethanol (ME), as release triggers. The biocompatibility and delivery efficiency of the MSN system with neuroglial cells (astrocytes) in vitro were demonstrated. In contrast to many current delivery systems, the molecules of interest were encapsulated inside the porous framework of the MSN not by adsorption or sol-gel types of entrapment but by capping the openings of the mesoporous channels with size-defined CdS nanoparticles to physically block the drugs/neurotransmitters of certain sizes from leaching out. We envision that this new MSN system could play a significant role in developing new generations of site-selective, controlled-release delivery nanodevices.     

Films of chitosan-based complexes with controlled release of Levomycetin

Complexation between chitosan and Levomycetin antibiotic and the possibility of formation of complexes of stoichiometric composition was studied.     

Preparation of thin polymer films with controlled drug release

Poly(N-isopropylacrylamide) (PAAm) is a thermal responsive polymer that undergoes a structural change in aqueous solution at its lower critical solution temperature (LCST). PAAm-modified silicon substrates were prepared and the effect of PAAm density on the thermal response of the modified surface was examined in terms of changes in the water contact angle as a basis for applying the structural change of the polymer to controlled drug release. Changes with temperature in the ability to load and release of the modified layer for drug were also examined using 2-acetoxybenzoic acid (aspirin) as a model drug. The amount of PAAm was found to greatly affect the thermal response and the ability to load and release of the modified layer for aspirin.     

Effects of topology and size on statics and dynamics of complexes of hyperbranched polymers with linear polyelectrolytes

Brownian dynamics simulations with explicit hydrodynamic interactions have been employed to study generic effects of size and topology in noncovalent (Coulombic-driven) complexes formed by irregular-shaped hyperbranched polymers and linear polyelectrolytes. The behavior of the complexes was explored in detail in terms of static and dynamic properties, both in local and in the entire complex scale. The results were compared to previous studies on perfect dendrimers and other hyperbranched molecules where available. It was found that both molecular weight and structure may impart significant changes to key factors known to be associated with the ability of these systems to take part in relevant nanoscale applications.     

Metal-polymer complexes of cobalt(II) and Copper(II) with hyperbranched polyester polycarboxylic acids

Hyperbranched polyester polycarboxylic acids of the second and third generations for use as high-efficiency complexing agents are synthesized. On the basis of these compounds, new metal-polymer complexes of cobalt(II) and copper(II) are prepared for the first time. As evidenced by IR and ERR studies, the central atom in these metal polycarboxylates occurs in the axially symmetric system MO₆. The thermal stability of polymer copper complexes is improved with increases in the content of metal ions, the degree of functionalization, and the generation number of the polyacid platform.     

Synthesis of pentablock and multibranched copolymers bearing poly(ethylene glycol), hyperbranched polyglycidol,and poly(L‐lactide) with biocompatibility for controlled drug release

A series of multibranched pentablock copolymer (mBr5BlC), poly(L ‐lactide)‐b‐HBP‐b‐poly(ethylene glycol)‐b‐HBP‐b‐poly(L ‐lactide) (HBP = hyperbranched polyglycidol), has been synthesized by ring‐opening multibranching polymerization of glycidol using bifunctional poly(ethylene glycol) [PEG; molecular weight (MW) = 1000] as an initiator, followed by ring‐opening polymerization (ROP) of L ‐lactide in the presence of stannous octoate. The ROP of different amounts of L ‐lactide on HBP‐b‐PEG‐b‐HBP [MW = 2550; polydispersity index (PDI) = 1.08] yielded a series of the targeted mBr5BlCs of the MW range of 4360–15,300 with narrow PDI. All the mBr5BlCs have been well demonstrated to be in possession of good biocompatibility as biomaterials for various applications in biological medicine areas. The mBr5BlCs with tunable MW exhibited promising controllability in self‐assembly into spherical micellar structures with an average diameter range of 59–140 nm, which have no acute and intrinsic cytotoxicity against normal cells and provide a convenient strategy for drug loading. The anticancer drug doxorubicin was demonstrated to have a good affinity with the copolymer system, and its controlled release was performed in various pHs. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Polynuclear copper(II) complexes with polydentate nanoligands on the basis of aminoderivatives of the hyperbranched polyesters

Coordinationally active polydentate nanoplatforms on the basis of amino-modified hyperbranched polyesters containing 7 terminal amino fragments are synthesized. Synthetic procedure is developed and polynuclear Cu(II) complexes with polyesteropolyamines are prepared. Their composition and stability of the complex forms in DMSO-water solutions are evaluated. It is found that all the compounds obtained exhibit biological activity with respect to the induced asparagine proteinase of Candida albicans.