Release Rate Of Doxorubicin Research Articles

Polymer microspheres with high drug-loading capacity via dual-modal drug-loading for modulating controlled release property in pH/reduction dual-responsive tumor-specific intracellular triggered doxorubicin release

pH/Reduction dual-responsive poly(4-formylphenyl acrylate-co-acryloyl-β-cyclodextrin) (P(FPA-co-ACD)) microspheres were synthesized as multi-functional vehicle for tumor-specific intracellular triggered doxorubicin (DOX) release, via emulsion copolymerization of acryloyl-β-cyclodextrin (ACD) and 4-formylphenyl acrylate (FPA), with N,N-bis(acryloyl)cystamine (BACy) as crosslinker. In comparison with the drug delivery system (DDS) via mono-modal drug-loading, the DOX/P(FPA-co-ACD)C via only covalent conjugation, or the DOX/P(FPA-co-ACD)N via only host-guest inclusion, the dual-modal drug-loaded DDS, DOX/P(FPA-co-ACD)C+N, were fabricated with a higher drug-loading capacity (DLC) of >53% via both acid-labile Schiff-base conjugation and host-guest inclusion complexation. Furthermore, the DOX release rate from the DOX/P(FPA-co-ACD)C+N was faster than the DOX/P(FPA-co-ACD)C but slower than the DOX/P(FPA-co-ACD)N in the simulated tumor intracellular microenvironment, demonstrating the controlled release behavior of such DDS could be modulated with dual-modal drug-loading.

Dual Responsive Polymersomes for Gold Nanorod and Doxorubicin Encapsulation: Nanomaterials with Potential Use as Smart Drug Delivery Systems.

In the present study, poly(ethylene glycol)-b-poly(N,N-diethylaminoethyl methacrylate) (PEG-b-PDEAEM) amphiphilic block copolymers were synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization using two different macro chain transfer agents containing PEG of 2000 and 5000 g/mol and varying the length of the PDEAEM segment. From the obtained block copolymers, polymersome type nanometric aggregates were obtained by two different techniques. By direct dispersion, particle diameters around 200 nm were obtained, while by solvent exchange using THF and water, the obtained diameters were around 100 nm. These block copolymers were used to encapsulate gold nanorods and doxorubicin (DOX) with good efficiencies to obtain nanomaterials with potential use as dual stimuli-sensitive drug delivery systems for combined anticancer therapies. Drug delivery studies showed that the release rate of DOX was accelerated when the pH was lowered from 7.4 to 5.8 and also when the systems were irradiated with a NIR laser at pH 7.4. The combination of lower pH and near infrared (NIR) irradiation resulted in higher drug release only in the case of polymersomes with lower molecular weight PEG.

Nanocarriers of Fe3O4 as a Novel Method for Delivery of the Antineoplastic Agent Doxorubicin Into HeLa Cells in vitro.

Here we report the synthesis and in vitro characterization of a redox-sensitive, magnetically inducible nanoparticle carrier system based on the doxorubicin (DOX) drug delivery model. Each quantal nanocarrier unit consists of a magnetite Fe3O4 nanoparticle core that is further encapsulated in self-assembled micelles of the redox-responsive polyethylene glycol derivative, DSPE-SS-mPEG. The nanocarrier system was prepared using a combination of ultrasonication and dialysis to produce the microenvironment sensitive delivery system. The final synthesized and DOX-loaded magnetic nanocarriers had an average size of ~150 nm when assembled with a 6.9% DOX payload. The release rate of DOX from these redox-responsive magnetic nanocarriers was shown to be accelerated in vitro when in the presence of glutathione (GSH). Furthermore, we demonstrated that more redox-responsive magnetic nanocarriers could be taken up by HeLa cells when a local magnetic field was applied. Once internalized within a cell, the micelles of the outer nanocarrier complex were broken down in the presence of higher concentrations of GSH, which accelerated the release of DOX. This produces a particle with dual operating characteristics that can be controlled via a specific cellular environment coupled with an exogenously applied signal in the form of a magnetic field triggering release.

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol copolymer based shell cross‐linked micelles for controlled release of drug

Amphiphilic block poly(propylene carbonate)‐block‐allyloxypolyethyleneglycol (PPC‐b‐APEG) copolymer was synthesized by the click chemistry, and its structure were characterized. PPC‐b‐APEG can self‐assemble into micelles without emulsifier in water. Shell cross‐linked micelles were obtained by the reaction of the allyloxy groups, which were exposed on the outer of the PPC‐b‐APEG micelles, and N‐vinylpyrrolidone (NVP). The morphology and size of the micelles before and after cross‐link reactions were characterized. The research result shows that the shell cross‐linking could improve the stability of micelles. The particle size of uncross‐linked micelle was about 800 nm. The size of cross‐linked micelles increased with increasing amount of cross‐linking degree. To better evaluate the release behavior of PPC‐b‐PEG copolymer, doxorubicin (DOX)‐loaded micelles were synthesized using DOX as the model drug. Results showed that the DOX releasing rate decreased with increasing of NVP. The shell cross‐linking do decrease the burst release behaviours of DOX and reduce the DOX release rate.

Functionalized Large-Pore Mesoporous Silica Microparticles for Gefitinib and Doxorubicin Codelivery.

Large-pore coralline mesoporous silica microparticles (CMS) were synthesized using the triblock polymer PEG-b-PEO-b-PEG and a hydrothermal method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the coralline morphology of the fabricated materials. The Brunauer–Emmett–Teller (BET) method and the Barrett–Joyner–Halenda (BJH) model confirmed the existence of large pores (20 nm) and of a tremendous specific surface area (663.865 m2·g−1) and pore volume (0.365 cm3·g−1). A novel pH-sensitive multiamine-chain carboxyl-functionalized coralline mesoporous silica material (CMS–(NH)3–COOH) was obtained via a facile “grafting-to” approach. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) validated the effective interfacial functionalization of CMS with carboxyl and multiamine chains. The encapsulation and release behavior of the dual drug (gefitinib (GB) and doxorubicin (DOX)) was also investigated. It was found that CMS–(NH)3–COOH allows rapid encapsulation with a high loading capacity of 47.36% for GB and 26.74% for DOX. Furthermore, the release profiles reveal that CMS–(NH)3–COOH can preferably control the release of DOX and GB. The accumulative release rates of DOX and GB were 32.03% and 13.66%, respectively, at a low pH (pH 5.0), while they reduced to 8.45% and 4.83% at pH 7.4. Moreover, all of the modified silica nanoparticles exhibited a high biocompatibility with a low cytotoxicity. In particular, the cytotoxicity of both of these two drugs was remarkably reduced after being encapsulated. CMS–(NH)3–COOH@GB@DOX showed tremendously synergistic effects of the dual drug in the antiproliferation and apoptosis of A549 human cancer cells in vitro.

Rod-Shaped Micelles Based on PHF-g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake

A biodegradable brush-type copolymer PHF- g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.

Multimodality imaging-guided local injection of eccentric magnetic microcapsules with electromagnetically controlled drug release.

In the past decade, trackable smart drug delivery systems have played important roles in the treatment of many diseases such as cancer because the drug carriers can be visualized through their distinct physical properties. However, it is still difficult to achieve precise drug delivery because such systems usually rely on a single imaging system. This study aimed to present a novel type of multimodality imaging-guided strategy to visualize the drug carriers of eccentric magnetic microcapsule (EMM) designed for potential treatment of hepatocellular carcinoma (HCC). The EMMs were prepared by using a three-phase microfluidic device. The as-prepared EMMs embedded with Fe3O4 nanoparticles are magnetic, with high density and acoustic impedance, allowing for visualization by magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US) imaging during local injection. The release of drug from these EMMs can be further controlled by an external electromagnetic field (EMF). As a proof of concept, we demonstrated the process of multimodality imaging to guide local injection and the controlled release of doxorubicin (DOX) from the EMMs in a phantom. We showed that the release rate of DOX was directly correlated to the strength of the EMF. In addition, we cocultured green fluorescent protein (GFP)-transfected HeLa cancer cells with the DOX-loaded EMMs and documented their apoptosis by DOX following the release triggered by EMF. The results suggest that these EMMs serve both as contrast agents that can be visualized by multimodality imaging techniques and as smart drug delivery systems, with great potential for precision medicine.

Green one-pot synthesis of carboxymethylcellulose/Zn-based metal-organic framework/graphene oxide bio-nanocomposite as a nanocarrier for drug delivery system

The aim of present work is to improve the solubility, surface charged and capacity of drug loading of graphene oxide (GO) by modification of GO with carboxymethylcellulose (CMC) and Zinc-based metal-organic framework (MOF-5) to realize and control accurately the release manner. To achieve this aim, carboxymethylcellulose/Zinc-based metal-organic framework/graphene oxide bio-nanocomposite (CMC/MOF-5/GO) as a new drug delivery system was synthesized in one-pot through the solvothermal technique. The prepared CMC/MOF-5/GO was characterized and used as a carrier to encapsulate the doxorubicin (DOX) as an anticancer drug. The obtained compounds were characterized using SEM, AFM, XRD, FTIR, EDX spectroscopy, BET and Zeta potentials-DLS analysis. The AFM images of GO and CMC/MOF-5/GO illustrated that the sheet thickness of GO was around 30 nm, which increased to ˜80 nm after modification with CMC and MOF-5.In addition, the drug delivery evaluation showed that the DOX-loaded bio-nanocomposites enhanced anticancer properties. Under tumor cell microenvironment at pH 5, the DOX release rate was significantly higher than that under physiological conditions at pH 7.4. The MTT results showed that DOX@CMC/MOF-5/GO exhibits notable cytotoxicity to K562 cells. The resulted bio-nanocomposite showed that this carrier system could be potentially used in anticancer drug delivery systems.

Iron oxide-pluronic F127 polymer nanocomposites as carriers for a doxorubicin drug delivery system

A multifunctional magnetic drug delivery system made up of an iron oxide nanoparticles (IONPs) core and a Pluronic F127 shell to carry Doxorubicin (DOX) was developed for neuroblastoma treatment. Several analytical techniques were then conducted to characterize the components of this system. The results showed that the prepared nanoparticles were nearly spherical ultrafine particles of 10–30 nm in diameter. Cryo–TEM images revealed the formation of a core-shell structure with different polydispersities and particle number densities. The hydrodynamic radius of the nanoparticles increased with increasing polymer concentration. The spectra of IONPs showed Fe2p and O1 s peaks at 700 and 530 eV, respectively, with binding energies associated with magnetite. The XANES spectra of the Fe atom in the different samples demonstrated an absorbance feature (Fe = 7112 eV) of a 1s to 3d transition. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results proved that the prepared nanocarriers were nontoxic when tested on BE–2–M17 cells. Moreover, the UV–vis spectra of DOX confirmed the successful conjugation of DOX with F127–IONPs. The in vitro drug release profile showed that the drug release from the F127–IONPs was pH sensitive, with a faster DOX release rate in acidic conditions than in a neutral environment.

Effects of surface modifications on the physicochemical properties of iron oxide nanoparticles and their performance as anticancer drug carriers

The feature of the surface coating can affect important properties of iron oxide nanoparticles (IONPs), it is therefore critical for further understanding how these materials react to physiological conditions, which is still needed to fully exploit the potential of IONPs for their theranostic applications. In this work, we prepared IONPs which surface were modified with citric acid (CA), chitosan (CS) and folic acid conjugated chitosan (FA-g-CS), respectively. Their physicochemical properties were investigated using FT-IR, TEM, powder XRD, VSM, TGA, DLS and zeta potential. We found that CA-IONP dispersion was composed of monocrystalline particles while CS-IONP and FA-g-CS-IONP were composed of polycrystalline aggregates. All IONPs retained the crystalline structure of magnetite and exhibited the superparamagnetic behavior. Their saturation magnetization decreased with the increase in the amount of their organic coatings. Their drug loading capacities, drug release patterns and in vitro anticancer efficiencies were studied by using doxorubicin (DOX) as a model drug. DOX@CS-IONP and DOX@FA-g-CS-IONP exhibited lower drug loading while showing higher water dispersity when compared with DOX@CA-IONP. All IONPs were surface charged and they tended to agglomerate in medium with high pH value and ionic strength. In the presence of chitosan or FA-g-CS coatings, their DOX release rate was slowed down compared with that of DOX@CA-IONP. Unloaded IONPs exhibited nearly no cytotoxicity on both cancer cells and normal cells in the presence of chitosan and FA-g-CS when compared with CA-IONP which presented high cytotoxicity. However, DOX@FA-g-CS-IONP showed significantly cytotoxicity on folate receptors (FRs) positive breast cancer cells while exhibiting nearly no cytotoxicity on FRs negative normal cells. Results presented in this study were valuable to the design and fabrication of IONPs-based system for better theranostic applications.

A perfect stimuli-responsive magnetic nanocomposite for intracellular delivery of doxorubicin

Iron oxide nanoparticles (IONs) have been extensively applied in cancer therapy and theranostics due to their admissible magnetic properties, excellent chemical stability and biocompatibility. Herein, a novel stimuli-responsive magnetic nanocomposite was synthesized for cancer therapy; thereby, the triblock copolymer of poly[(2-succinyloxyethylmethacrylate)-b-(N-isopropylacrylamide)-b-dimethylaminoethylmethacrylate) [poly(SEMA-b-NIPAM-b-DMAEMA)] was prepared by reversible addition of fragmentation chain transfer (RAFT) polymerization. This triblock copolymer with carboxylic groups of succinyloxyethylmethacrylate was adsorbed onto the surface of Fe3O4 nanoparticles. The morphology, nanocomposite properties and stimuli-responsive behaviours were investigated by field emission scanning electron microscopy, X-ray diffraction, dynamic light scattering, vibrating sample magnetometer (VSM) and thermogravimetric analysis. Doxorubicin (DOX) encapsulation efficacy was 94.3%. Release behaviours of DOX from the magnetic nanocomposite exhibited that the rate of DOX release could be efficiently controlled through temperature and pH. The cytotoxicity of the drug was investigated in vitro against breast cancer cell line (MCF7) using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assays, 4′,6-diamidino-2-phenylindole (DAPI) staining and cellular uptake. In conclusion, the synthesized DOX@nanocomposite can be applied in theranostic applications and anticancer drug delivery owing to admissible properties.

PH-Responsive fluorescent dye-labeled metal-chelating polymer with embedded cadmium telluride quantum dots for controlled drug release of doxorubicin

This paper describes the synthesis and characterization of a pH-responsive drug release system based on cadmium telluride quantum dots capped by fluorescent dye-labeled poly (N-(2-(2-amino-ethylamino)-ethyl methacrylamide) metal-chelating polymer. Fluorescent dye is a model for an active molecule which shows our polymer can be attached to bioactive agents such as antibody or a functional drug. Furthermore, it indicates the success of ligand exchange between anchor groups on polymer surface and QDs. The polymer was synthesized using reversible addition fragmentation chain transfer polymerization, resulting in polymers with controllable molecular weights and low polydispersities. The use of diethylenetriamine allows obtaining hydrophilic polymers with amine functional groups available for conjugation with QDs. Furthermore, the amine moieties of the polymer guarantee the pH sensitivity of the system. The obtained nano carrier was monodispersed with very small diameter around 4.5 nm which confirmed by TEM. The obtained nanoparticles show low cytotoxicity in cell viability studies. The release rates of doxorubicin (DOX) anticancer drug conjugates were studied at pH 5.4 and pH 7.4. The release behavior for DOX in pH 7.4 (pH of normal cells) is <1%, while it is high at pH 5.4 (pH of cancer cells).

Multifunctional Dendrimer-Entrapped Gold Nanoparticles Conjugated with Doxorubicin for pH-Responsive Drug Delivery and Targeted Computed Tomography Imaging.

Novel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

ABSTRACTTemperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46714.

Effective pH-Activated Theranostic Platform for Synchronous Magnetic Resonance Imaging Diagnosis and Chemotherapy

Current magnetic resonance imaging (MRI)-guided pH-switching therapeutic platforms have encountered problems such as low relaxation rates, poor pH-switching efficiencies, and a lag in the drug release behind the MRI. Herein, we designed a nanoplatform with tunable pore size, which could match the size of drug molecules for pH-switching MRI and chemotherapy via ultrasmall manganese oxide-capped mesoporous silica nanoparticles (USMO@MSNs). USMO@MSN could quickly dissolve under weakly acidic conditions and leach abundant Mn2+ ions (leaching ratio: 76%), enhancing the MR contrast. The longitudinal relaxation rate ( r1) of USMO@MSNs significantly increased from 0.65 to 5.61 mM-1 s-1 as the pH decreased from 7.4 to 4.5, showing an ultrahigh-efficiency pH-switching T1-weighted MR contrast ability for in vivo tumor. Meanwhile, the matching pore structure allowed effective loading of doxorubicin (DOX) on USMO@MSNs to form smart therapeutic system (USMO@MSNs-DOX). The DOX release rate was strongly proportional to the pH-switching MRI signal of USMO@MSNs-DOX, allowing the release of DOX to be efficiently monitored by MRI. Confocal observations indicated that USMO@MSNs-DOX could be effectively internalized by HSC3 cells, and the entire system showed a good pH-switching theranostic performance for HSC3 cells. Therefore, this simple pH-switching system provides a new avenue for timely cancer diagnosis and personalized therapy.

Reduction/temperature/pH multi-stimuli responsive core cross-linked polypeptide hybrid micelles for triggered and intracellular drug release

The high toxicity, poor stability, premature drug release, and lack of intracellular stimuli responsibility of current polymeric micelles still hinder them for potential clinical applications. To address these challenges, a novel type of multi-stimuli responsive, core cross-linked polypeptide hybrid micelles (CCMs) was developed for triggered anticancer drug delivery in tumor microenvironment. The CCMs was prepared via free radical copolymerization by using N,N'-methylene-bis-acylamide (BACy) as the cross-linking agent, 2,2-azobisisobutyronitrile (AIBN) as the initiator, where poly (γ-benzyl-L-glutamate) (PBLG) and N-isopropylacrylamide (NIPPAM) as comonomers. The doxorubicin (DOX) was then introduced into the CCMs by hydrazone bond to prepare the drug-incorporated core cross-linked micelles (CCMs-DOX). By the experimental results, the CCMs showed reduction responsibility due to the degradable disulfide bond in the polymer network. The hydrazone bond can be broken under acidic condition causing a controllable drug release for CCMs-DOX. Compared to only 7.7% DOX release under pH 7.4 at 37°C, a much higher DOX release rate up to 85.3% was observed under 10 mM GSH (pH 5.0, 42°C). In vitro cell assays showed that the blank CCMs showed almost no toxicity against HUVEC cells while the CCMS-DOX exhibited significant cancer cell killing effect. These experimental results suggested that the prepared multi-stimuli responsive polymeric micelles could serve as a smart and promising drug delivery candidate for anti-cancer therapy.

Preparation and characterization of pectin/chitosan beads containing porous starch embedded with doxorubicin hydrochloride: A novel and simple colon targeted drug delivery system

The objective of this study was to design a simple, colon targeted drug delivery system by using porous starch (PS), pectin and chitosan. Porous maize starch was prepared by hydrolysis with a combination of α-amylase and amyloglucosidase, and it was characterized by scanning electron microscopy, revealing the formation of porous structures in the starch granules. A Brunauer-Emmett-Teller (BET) specific surface area analysis indicated that the specific surface area of the PS (0.8768–0.9448 m2/g) was 19.88–21.42 times larger than that of native maize starch (0.0441 m2/g). The average pore diameter of the PS granules, as calculated by the Barrett-Joiner-Halenda (BJH) method, was 40.52–62.42 nm. A favorable adsorptive potential of the PS granules was verified by water and soybean oil tests. Doxorubicin was loaded into PS granules, which were then coated with a pectin/chitosan complex solution. The results of confocal laser scanning microscopy (CLSM) demonstrated that doxorubicin was successfully absorbed into the PS granules. In addition, an in vitro simulated digestion method demonstrated the effectiveness of this delivery design, as only a 13.80% release rate of doxorubicin was observed in the upper gastrointestinal tract, whereas release rates of 17.56% and 67.04% were observed for pectin/PS/doxorubicin and pectin/doxorubicin beads, respectively. It was concluded that the use of PS and a pectin/chitosan coating is an effective method for colon targeted drug delivery compared with the simple polysaccharide system.

Thermo/pH/magnetic-triple sensitive poly(N-isopropylacrylamide-co-2-dimethylaminoethyl) methacrylate)/sodium alginate modified magnetic graphene oxide nanogel for anticancer drug delivery

Herein, thermo/pH/magnetic-triple sensitive nanogel comprised of poly(N-isopropylacrylamide), poly(2-dimethylaminoethyl) methacrylate), sodium alginate, and magnetic graphene oxide were synthesized using N,N-methylenebisacrylamide as a crosslinking agent, sodium dodecylsulfate as a surfactant, and ammonium persulfate as an initiator. The size, chemical structure, thermal stability, and morphology of the prepared nanogel were characterized using different methods. Transmittance of the obtained nanogel was investigated at varying pH and temperature in the presence and absence of magnet. The drug loading ability of synthesized nanogel was examined at different times and concentrations of doxorubicin. Additionally, the release rate of doxorubicin as an anticancer drug from the loaded nanogel was studied at different pH and temperature in the presence and absence of magnet. The biological performance of the formed nanogel was evaluated by seeding it onto MCF-7 cells at different times and concentrations. It was found that this triple responsible nanogel might provide a perfect basis for controlled drug delivery systems.

Hypoxia-Responsive Mesoporous Nanoparticles for Doxorubicin Delivery.

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper portion of CD-HR-MSNs disintegrated through bioreduction of the hydrophobic NI state to the hydrophilic NI state. Under hypoxic conditions, the release rate of doxorubicin (DOX) from DOX-loaded CD-HR-MSNs (DOX-CD-HR-MSNs) increased along with the disintegration of the gatekeeper. Conversely, DOX release was retarded under normoxic conditions. In vitro experiments confirmed that DOX-CD-HR-MSNs exhibit higher toxicity to hypoxic cells when compared to normoxic cells. Confocal microscopy images indicated that DOX-CD-HR-MSNs effectively release DOX into SCC-7 cells under hypoxic conditions. These results demonstrate that CD-HR-MSNs can release drugs in a hypoxia-responsive manner, and thus are promising drug carriers for hypoxia-targeted cancer therapy.

Simulation of Stimuli-Responsive and Stoichiometrically Controlled Release Rate of Doxorubicin from Liposomes in Tumor Interstitial Fluid.

To simulate the stimuli-responsive and stoichiometrically controlled doxorubicin (DOX) release from liposomes in in vivo tumor interstitial fluid (TIF), the effect of ammonia concentration and pH on the DOX release from liposomes in human plasma at 37°C was quantitatively evaluated in vitro and the release rate was calculated as a function of ammonia concentration and pH. Human plasma samples spiked with DOX-loaded PEGylated liposomes (PLD) or Doxil®, containing ammonia (0.3-50mM) at different pH values, were incubated at 37°C for 24h. After incubation, the concentration of encapsulated DOX in the samples was determined by validated solid-phase extraction (SPE)-SPE-high performance liquid chromatography. Accelerated DOX release (%) from liposomes was observed as the increase of ammonia concentration and pH of the matrix, and the decrease of encapsulated DOX concentration. The release rate was expressed as a function of the ammonia concentration and pH by using Henderson-Hasselbalch equation. The DOX release from PLD in TIF was expressed as a function ammonia concentration and pH at various DOX concentrations. Further, it was found that the DOX release from liposomes in a simulated TIF was more than 15 times higher than in normal plasma.