Release Rate Of DOX Research Articles

Development of a Negative-Biased Zwitterionic Polypeptide-Based Nanodrug Vehicle for pH-Triggered Cellular Uptake and Accelerated Drug Release.

Albumin mimics could be an attractive platform for nanodrug carriers through systematic administration because of high safety and plentiful properties to be adjusted for a high drug efficacy, such as pH-triggered targeting cellular uptake and drug release. In this work, negative-biased zwitterionic nanodrug carriers based on zwitterionic polypeptide chains that mimic albumin were prepared, which have an outermost layer of zwitterionic glutamic acid (E) and lysine (K) pairs with a small amount of aspartic acid (D) to adjust the overall ζ potential. On the other hand, doxorubicin (Dox) was encapsulated in a hydrophobic core by 11-maleimidoundecanoic acid covalently linked with additional cysteine (C) residues on the polypeptide. The results show that the negative-biased zwitterionic nanodrug carriers can sensitively enhance the cellular uptake in responding to a pH change from 7.4 to 6.7 without reversing the ζ potential to a positive charge, leading to accelerating the Dox release rate in a slightly acidic environment through the polypeptide secondary structure change. Moreover, the anionic nanodrug carrier can also be easily enzymatically digested by trypsin for quick drug release. In short, this negative-biased zwitterionic nanodrug delivery vector could be an ideal candidate for a safer tumor inhibition with a high efficacy than conventional synthetic polymer-based ones.

PH-sensitive bromelain nanoparticles by ortho ester crosslinkage for enhanced doxorubicin penetration in solid tumor.

Dense extracellular matrix (ECM) is a primary obstacle that restrains the permeation of therapeutic drugs in tumor tissues. Degrading ECM with bromelain (Br) to increase drug penetration is an attractive strategy to enhance antitumor effects. However, the poor stability in circulation and potential immunogenicity severely limit their applications. In this work, a novel pH-sensitive nanocarrier was prepared by crosslinking Br with an ortho ester-based crosslink agent, and Br still retained a certain ability to degrade ECM after crosslinking. The nanoparticles showed higher DOX release rate than non-sensitive nanoparticles, and DOX release amount reached to 86% at pH5.5 within 120h. In vivo experiments revealed that the pH-sensitive nanoparticles could be degraded in mildly acidic condition, and the released Br further promoted nanoparticles penetration in tumor parenchyma via in situ hydrolysis of ECM. Furthermore, Br itself could inhibit the proliferation of tumor cells at high concentration, and produce synergistic antitumor effects with DOX. Finally, tumor growth inhibition of these nanoparticles reached to 62.5%. Overall, the bromelain-based pH-sensitive nanoparticles can be potential drug carriers for efficient drug delivery and tumor treatment.

ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy

Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.

"Two in one": Simultaneous functionalization and DOX loading for fabrication of nanodiamond-based pH responsive drug delivery system.

Nanodiamond (ND) has been widely studied as a new type of carbon nanomaterials that is expected to be used as a promising candidate in various fields especially in the field of biomedicine. However, its poor water dispersibility and insufficient controlled release limit its practical applications. In this paper, ND-based composites with pH-responsive hydrazone bonds were successfully prepared by a simple chemical reaction between ester groups and hydrazine hydrate, in which ester groups were conjugated on the surface of ND via thiol-ene click reaction. On the other hand, CHO-PEG and doxorubicin hydrochloride (DOX) were linked on the carriers through formation of hydrazone bonds, resulting in improving water dispersibility and high drug loading capacity. The structure, thermal stability, surface morphology and particle size of ND carriers were characterized by different equipment. Results demonstrated that we have successfully prepared these functionalized ND. The release rate of DOX in acidic environment was significantly greater than that in normal physiological environment. More importantly, cell viability and optical imaging results showed that ND-based composites possess good biocompatibility, therapeutic effect, and could successfully transport DOX to HepG2 cells. Considering the above results, we believe that our new ND carriers will become promising candidates for intracellular controlled drug delivery and cancer treatment.

Supramolecular Valves Functionalized Rattle-Structured UCNPs@hm-SiO2 Nanoparticles with Controlled Drug Release Triggered by Quintuple Stimuli and Dual-Modality Imaging Functions: A Potential Theranostic Nanomedicine.

Integrating multimodality bioimaging and multiple stimuli-responsive controlled drug release properties into one single nanosystem for therapeutic application is highly desirable but still remains a challenge. Herein, we coated a hollow mesoporous silica shell on to upconversion nanoparticles (UCNPs) and conjugated pillarene-based supramolecular valves on to surface of UCNPs@hm-SiO2 using amine-coumarin phototriggers to obtain the multifunctional nanoparticles, UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5]. Benefiting from the core-shell structured UCNPs, the UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5] can serve as efficient contrast agents for upconversion luminescence and T1-weighted magnetic resonance imaging in vitro/in vivo. More importantly, depending on exquisitely designed supramolecular valves, UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5] can realize zero-premature release under normal physiological conditions (pH 7.4), which produces minimal damage to normal tissue, whereas this nanosystem can respond to several disease-related signals, including acid (most cancers), alkali (metabolic alkalosis), and Zn2+ (Alzheimer's disease), along with two external stimuli, including near-infrared (NIR) light and reductive electrical potential, via altering the spatial structure of pseudorotaxanes, disassembling the molecular stalks, or undergoing photochemical reactions, ultimately resulting in opening of the gatekeepers and release of encapsulated drugs. The multifunctional UCNP-based nanoparticles were endowed with such quintuple stimuli-responsive controlled release characteristics. Specifically, in anticancer application, the rational utilization of the two of them, acid and NIR light, could regulate the release amount and rate of DOX from UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5], accelerate the accumulation of DOX in cell nuclei, and thereby promote the cancer cell apoptosis, indicating that the nanomaterials have promising application in cancer treatment. This study provides a novel design strategy for constructing multifunctional UCNP-based nanoparticles with multiple stimuli-responsive drug release features, which have great potential in diagnosis and therapy of relevant diseases as theranostic nanomedicines.

PH-Responsive diblock copolymers made of ω-pentadecalactone and ionically charged α-amino acids

Two sets of ionically charged polypentadecalactone-polypeptide diblock copolymers (PPDLx-b-PAAy, with x = 15 or 20 and y ranging from 30 to 200), one containing α-L-glutamic acid (LGA) and the other containing α-L-lysine (LL), were obtained from their respective precursors with the side groups of LGA and LL protected as γO-benzyl and εN-carbobenzoxy, respectively. The copolymers were semicrystalline with the polyester block crystallized in the usual pseudo-rhombic lattice and the polypeptide in the α-helix or β-sheet conformation depending on the amino acid and the length of the block. Copolymers with PAA blocks with y ≥ 80 were water-soluble and they adopted the α-helix conformation in the aqueous medium when they are in the non-ionized state. Both LGA and LL containing copolymers self-assembled in nanoparticles with a size between 150 and 180 nm in diameter. PPDL-b-PLGA nanoparticles were able to load DOX with an efficiency of ~70% whereas PPDL-b-PLL displayed a noticeable capacity for condensing DNA. In both cases hosting was based on the ionic complexation taking place between the ionized copolymer and the guest compound. Accordingly DOX release rate was found to be noticeably depending on pH.

Self-healing hydrogel with cross-linking induced thermo-response regulated light emission property

With increasing attention paid to smart materials, self-healing hydrogels with thermo-responses have been greatly developed in the past several years. At the same time, fluorescent or light emitting polymers have been studied for use as bioimaging tools and drug delivery vehicles. In this research, thermo-responsive self-healing hydrogels with aggregation-induced emission (AIE) property were prepared from tetraphenylethylene (TPE) containing TPE-poly(N,N-dimethylacrylamide-stat-Diacetone acrylamide) [TPE-P(DMA-stat-DAA)] cross-linked by diacylhydrazide. In addition to self-healing based on reversible acylhydrazone bond, the copolymer and hydrogels showed thermo-responses. The lower critical solution temperature (LCST) of the hydrogels was regulated to body temperature. Based on the AIE property of the TPE unit, the hydrogels showed an enhanced light emitting property above the LCST, which was regulated by temperature change. The in vitro cytotoxicity experiment showed that the hydrogels are not toxic, and the DOX release rate can be enhanced by low pH values, which endowed this kind of thermo-responsive light emitting hydrogel with great potential for applications in bio-diagnosis, drug delivery, artificial organs with light sensitive detection, etc.

Encapsulation and release of doxycycline from electrospray-generated PLGA microspheres: Effect of polymer end groups

The aim of this study was to investigate the influence of end group of poly(lactic-co-glycolic acid) (PLGA) on the drug loading and release behavior of electrospray-generated PLGA microspheres. To this end, doxycycline hyclate (DOX) was selected as a model drug, and PLGA (molecular weight: 17 and 44 kDa) with either an acid or ester end group were electrosprayed with DOX. The processing parameters were optimized to obtain microspheres comparable in size. Drug loading efficiency and release profile were determined by the high-performance liquid chromatography-ultraviolet detection (HPLC-UV) method. PLGA polymers or drug-loaded microspheres were characterized before and after exposure to phosphate buffer saline at 37 °C regarding the wettability of polymers, pH changes of the buffer, molecular weight of PLGA and morphology of the microspheres. The acid end group of PLGA microspheres brought about lower encapsulation efficiency and faster DOX release rate in our study, indicating that different hydrophilicity of polymer and degradation speed were the main reasons causing a difference in encapsulation efficiency and release profile. In addition, DOX released from the PLGA microspheres was active by showing antibacterial effects against Porphyromonas gingivalis as measured using a zone of inhibition test, and varying the end groups showed no impact on the antibacterial efficacy. This study demonstrated that the end group of PLGA can be used as a new tool to regulate drug encapsulation efficiency and release rate to meet different clinical drug delivery requirements.

Natural Salep/PEGylated Chitosan Double Layer toward a More Sustainable pH-Responsive Magnetite Nanocarrier for Targeted Delivery of DOX and Hyperthermia Application

Two pH-responsive polysaccharide-based magnetite nanocarriers have been developed from modified salep and PEGylated chitosan decorated onto the surface of magnetite nanoparticles for active loading and targeted delivery of doxorubicin. The first nanocarrier was formed via imine bond formation and electrostatic hydrogen bonding interactions between dialdehyde salep-modified magnetite nanoparticles and DOX in a one-layered nanocarrier fashion. Subsequently, PEGylated chitosan was used as a second layer on the surface of the first nanocarrier, mainly by the same interactions, producing a double-layered polysaccharide-based nanocarrier. In vitro release studies indicated that the use of PEGylated chitosan as the second shell provides more control on the rate and amount of DOX release and makes double-layered nanocarrier more pH-sensitive. Magnetic heating capacity of double-layered nanocarrier was investigated and release profile under AMF (42 °C, magnetically induced) showed a good improvement in the time an...

Preparation of dual-targeted pH-sensitive DOX prodrug-microbubble complex and drug release experiment in vitro

Objective To prepare dual-targeted pH-sensitive DOX prodrug-microbubble complex and explore the characterization of complex with ultrasound as well as drug release in vitro. Methods Dual-targeted ligands, cRGD and folate were conjugated with heparin using carbodiimide method, and then the dual-targeted pH-sensitive DOX prodrug was synthesized by coupling DOX via a pH-sensitive hydrazone bond. The prodrug was combined with microbubbles to prepare complex by biotin-avidin system. The characterization of complex with/without ultrasound was investigated for size, morphology and drug loaded capacity.In vitro drug release manner of complex with/without at different pH was analyzed. Results DOX content of the prodrug determined by UV Spectrophotometry was about 18.9%. Dynamic laser light scattering analysis(DLS), corresponding to transmission electron microscope(TEM) findings, revealed its inhomogeneous size distribution [mean size (159.7±24.5)nm and (1 089.0±174.9)nm]. However, the complex was dispersed into uniform fragment after ultrasound irradiation[mean size (155.9±29.8)nm, polymer dispersity index(PDI) 0.22, Zeta potential -(20.6±3.4)mV]. The cumulative release rate of DOX from both complex and complex with ultrasound at pH 5.0 were much faster than that at pH 7.4, displaying a pH-triggered release manner. Conclusions Dual-targeted pH-sensitive DOX prodrug-microbubble complex displays excellent drug release activity in acid environment. Uniform fragment and smaller particle size of complex could be achieved via ultrasound irradiation, promoting DOX accumulation within tumor tissue and facilitating in vivo antitumor ability. Key words: Sonication; Doxorubicin; Microbubbles; Targeted therapy

Preparation and characterization of an injectable thermosensitive hydrogel for simultaneous delivery of paclitaxel and doxorubicin.

In the current study, we aimed to develop a novel injectable thermosensitive hydrogel for simultaneous intra-tumoral administration of paclitaxel (PTX) and doxorubicin hydrochloride (DOX). At first, mixed micelles composed of Pluronic F127 and α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was loaded with PTX and their physicochemical properties including particle size, zeta potential, drug loading content, entrapment efficiency, and the drug release were investigated in details. In the second step, the optimized PTX-loaded micelles prepared in the first step were incorporated into the thermosensitive Pluronic F127/hyaluronic acid (PF127/HA) hydrogel containing fixed amount of DOX. Gel formation temperature, rheological properties, injectability, degradation rates of the hydrogel, and the release rate of PTX and DOX from the hydrogel were examined. The mean particle sizes and zeta potentials of the PTX-loaded micelles were 157.5 ± 20.1 nm and -9.6 ± 1.1 mV, respectively. The entrapment efficiency of the formulation was about 51%. The hydrogel containing PTX-loaded micelles and DOX existed as a solution with low viscosity at 4 °C converted to a semisolid upon increasing the temperature to 35 °C. DOX was completely released from the hydrogel within 12 h, while 40-80% of PTX could be released from the different formulations during 3 days. This novel thermosensitive hydrogel prepared in the current study could be efficiently used for co-delivery of PTX and DOX in solid tumor types.

Doxorubicin Adsorbed on Carbon Nanotubes: Helical Structure and New Release Trigger

AbstractThe well‐known drug delivery system “doxorubicin physically loaded on carbon nanotubes” (Dox@CNT) is visualized by scanning tunneling microscopy at the molecular level, revealing rich architectural variability of Dox@CNT, and allowing to measure and rationalize reported loading efficiencies (80–200%) for the first time from image analysis. Reduction of Dox@CNT is identified as a so far unknown intrinsic release mechanism of biochemically relevance for Dox from Dox@CNT requiring no further CNT surface modification beside Dox loading. Electron injection into Dox@CNT from an electrode or from the biological reducing agent glutathione (GSH) leads to irreversible release of Dox. Its rate follows a linear free energy relationship (reduction potential vs log (Dox release rate)) with half‐life times from below seconds to hours. With extracellular GSH levels in the micromolar range and intracellular GSH concentrations of 10 × 10−3m or even higher, the findings can explain the preferential intracellular release of Dox from its physically adsorbed state on CNTs. The influence of acidity on the release rate of Dox on pristine 6,5‐CNTs in the absence of GSH is found to be negligible. The experimental findings are strongly supported by semi‐empirical calculations.

Fabrication of chitosan/poly(lactic acid)/graphene oxide/TiO2 composite nanofibrous scaffolds for sustained delivery of doxorubicin and treatment of lung cancer

In this work, the synthesized graphene oxide/TiO2/doxorubicin (GO/TiO2/DOX) composites were loaded into the chitosan/poly(lactic acid) (PLA) solutions to fabricate the electrospun chitosan/PLA/GO/TiO2/DOX nanofibrous scaffolds via electrospinning process. The synthesized composites and nanofibers were characterized using X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis. Three-factor three-level central composite design was used to determine the influence of PLA to chitosan ratio, TiO2/DOX content and GO/TiO2/DOX content on the release of DOX from nanofibrous scaffolds. Drug loading efficiency and drug release behavior from nanofibers were investigated. The higher sustained release rate of DOX following the small burst release were achieved from nanofibrous scaffolds with 30 and 50μm thicknesses within two weeks incubation time. The faster DOX release rate from nanofibers was obtained in pH 5.3 compared to pH 7.4. Korsmayer-Peppas kinetic model was used to determine the DOX release mechanism from nanofibers. The cell viability results showed the higher proliferation inhibition effect of nanofibers on target lung cancer cells in the presence of magnetic field.

Sequential delivery of erlotinib and doxorubicin for enhanced triple negative Breast cancer treatment using polymeric nanoparticle

Recent studies of signaling networks point out that an order of drugs to be administrated to the cancerous cells can be critical for optimal therapeutic outcomes of recalcitrant metastatic and drug-resistant cell types. In this study, a development of a polymeric nanoparticle system for sequential delivery is reported. The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties [i.e. epidermal growth factor receptor (EGFR) inhibitor, erlotinib (Ei), and doxorubicin (Dox)]. Dox is hydrophilic and was complexed with anionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), via ion pairing to form a hydrophobic entity. Then it was co-encapsulated with hydrophobic Ei in a poly(L-lactide)-b-polyethylene glycol (PLA-b-PEG) nanoparticle by nanoprecipitation. The complexation of Dox with DOPA greatly helps the encapsulation of Dox, and substantially reduces the release rate of Dox. This nanoparticle system was found to burst the release of Ei with a slow and sustained profile of Dox, which is an optimal course of administration for these two drugs as previously reported. The efficacy of this sequential delivery nanoparticle system was validated in vitro and its in vivo potential applicability was substantiated by fluorescent imaging of high tumor accumulation.

Molecularly imprinted cryogel as a pH-responsive delivery system for doxorubicin

ABSTRACTIn this study, implantable and degradable molecularly imprinted cryogel was prepared for pH-responsive delivery of doxorubicin. Cryogel discs were synthesized using amino acid-based functional monomer with HEMA and gelatin. The molecularly imprinted discs were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, degradation and swelling tests. In vitro delivery experiments were carried out in order to examine the effects of medium pH and drug content. The degree of degradation of composite cryogels was found to be 83.45±1.86% after 56 days. The release profiles of DOX from molecularly imprinted cryogel discs exhibit a biphasic delivery. It was observed that an initial burst release step from 0 to 12 h was followed by a slower and sustained release. Release rate of DOX from cryogel discs increased in more acidic conditions. Kinetic studies showed that a combination of diffusion and erosion control is mainly responsible from the general release behaviors of molecularly imprinted cryogel discs.

Novel reduction-sensitive micellar nanoparticles assembled from Rituximab-doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non-Hodgkin's lymphoma.

In this study, a novel reduction-sensitive drug delivery system, the rituximab-doxorubicin (RTX-DOX) micellar nanoparticle (RDMN), was specially designed for targeted delivery and release of DOX in non-Hodgkin's lymphoma (NHL) cells. The RDMN was fabricated by self-assembling of amphiphilic RTX-DOX conjugates (RDCs), which were synthesized by conjugating the hydrophilic Fab fragments of RTX (an anti-CD20 monoclonal antibody) and hydrophobic DOXs by a reduction-responsive linker, 3-(2-Pyridyldithio) propionyl hydrazide (PDPH). The RDMNs were characterized via dynamic light scattering and transmission electron microscopy, both showed the sizes of approximately 94.1±14.5nm with a uniform size distribution. Polyplex dissociation, which was indicated by accelerated DOX release rate and increased particle size, was observed in the presence of 2.5mm 1,4-dithiothreitol due to the cleavage of disulfide bonds in PDPH linkers. In vitro transfection assays against human NHL cell line, JeKo-1, showed significantly increased uptake for RDMNs, as compared to RDCs and free RTX/DOX. Both in and ex vivo experiments demonstrated that RDMNs showed the highest therapeutic effect among all the experimental groups. These results suggested that this RDMN could be a potential, safe and efficient drug delivery vector, which deserves further investigation in the clinic.

Anti-melanotransferrin and apolipoprotein E on doxorubicin-loaded cationic solid lipid nanoparticles for pharmacotherapy of glioblastoma multiforme

Abstract Cationic solid lipid nanoparticles (CSLNs) with surface anti-melanotransferrin (AMT) and apolipoprotein E (ApoE) were used to carry antimitotic doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) treatment. Dox-loaded CSLNs (Dox-CSLNs) were prepared in microemulsion, grafted covalently with AMT and ApoE, and applied to human brain-microvascular endothelial cells (HBMECs), human astrocytes, and U87MG cells. An increase in the weight percentage of stearylamine (SA) and a decrease in the stirring rate enhanced the particle size and the absolute value of the zeta potential of AMT-ApoE-Dox-CSLNs. In addition, the encapsulation efficiency of Dox in CSLNs decreased with increases in the weight percentage of Dox and the order in the encapsulation efficiency of Dox was 10% SA > 20% SA > 0% SA. However, the reverse order was true for the release rate of Dox, suggesting that AMT-ApoE-Dox-CSLNs containing 10% SA had better characteristics of sustained release. Moreover, AMT-ApoE-Dox-CSLNs fabricated at 10 µg/mL of ApoE could slightly reduce the transendothelial electrical resistance and increase the permeability of propidium iodide. AMT-ApoE-Dox-CSLNs did not induce serious cytotoxicity to HBMECs, and AMT-ApoE-Dox-CSLNs fabricated at 10 µg/mL of AMT and at 5–10 µg/mL of ApoE could significantly enhance the permeability of Dox across the BBB. The order in the efficacy of inhibiting U87MG cells was AMT-ApoE-Dox-CSLNs > AMT-Dox-CSLNs > Dox-CSLNs > Dox. Hence, AMT-ApoE-Dox-CSLNs have appropriate physicochemical properties and can be a potential colloidal delivery system for brain tumor chemotherapy.

Engineered Doxorubicin Delivery System Using Proteinoid-Poly (L-Lactic Acid) Polymeric Nanoparticles of Narrow Size Distribution and High Molecular Weight for Cancer Treatment

Doxorubicin (Dox), a widely used anti-cancer drug, was encapsulated within new special-tailored proteinoid nanoparticles (NPs), with the intention to overcome side effects while keeping the drug potency. The synthesis and characterization of four newly-made proteinoids of very high molecular weights (122-149 kDa) and low polydispersity (1.01-1.03) is presented. The proteinoids were synthesized from L-lysine, L-arginine, L-histidine, L-phenylalanine and poly-L-lactic acid (PLLA) segments, and are named P(KRHF-PLLA). Using this selection of amino acids provides basic positive-charged novel tailored proteinoids, with a rigid and biodegradable backbone, achieved by the incorporation of PLLA. The proteinoids self-assemble to yield NPs of a narrow-size distribution. This self-assembly procedure was utilized to encapsulate Dox within the NP core. The optimal Dox-encapsulated NPs were chosen by a study of their size, size distribution and Dox content. The chosen NPs, 15% Dox-loaded P(KRHF-PLLA) NPs were checked for their stability in different conditions. In order to improve tumor uptake and time of circulation in the blood, the chosen NPs were further PEGylated and the effects of PEGylation of the NPs, as well as the effect of the environment, on the release rate of Dox from the NPs were investigated. Additionally, the cytotoxicity of the PEGylated and non-PEGylated Dox-containing NPs was studied by XTT assay and their generation of immune-response was investigated by cytokines induction assay. Overall, the Dox-loaded NPs were found stable, non-immunogenic and showed good cell toxicity, making them good candidates to be used against cancer, while PEGylation improved all parameters.

Hollow mesoporous ZSM-5 zeolite/chitosan ellipsoids loaded with doxorubicin as pH-responsive drug delivery systems against osteosarcoma.

The toxic risks and adverse effects of anticancer drugs on healthy tissues limit their wide clinical application. Herein, we for the first time fabricated hollow mesoporous ZSM-5/chitosan ellipsoids loaded with doxorubicin (HM-ZSM-5/CS/DOX) as pH-responsive drug delivery systems against osteosarcoma. The HM-ZSM-5 ellipsoids including a hollow core and a mesoporous shell could efficiently load DOX drugs with a loading efficiency of 95.8%. The CS layer was uniformly distributed on the HM-ZSM-5 ellipsoids that contributed to the pH-responsive release of DOX drugs. The controlled DOX release kinetics from the HM-ZSM-5/CS/DOX ellipsoids was fitted well with the Korsmeyer-Peppas model. The HM-ZSM-5/CS/DOX ellipsoids exhibited good biocompatibility due to the low DOX release rate in the neutral media that simulated healthy tissues or blood. Moreover, the cellular uptake of the HM-ZSM-5/CS/DOX ellipsoids took place in tumor cells, and the quick release of DOX significantly promoted the apoptosis of MG63 cells. The levels of MDA, LDH and CK markers for the HM-ZSM-5/CS/DOX group were lower than those for the free DOX group, suggesting no systemic toxicity to the heart. Therefore, the HM-ZSM-5/CS/DOX ellipsoids as novel pH-responsive drug delivery systems can effectively treat osteosarcoma without systemic toxicity.

Bioinspired Coordination Micelles Integrating High Stability, Triggered Cargo Release, and Magnetic Resonance Imaging.

Catechol-Fe3+ coordinated micelles show the potential for achieving on-demand drug delivery and magnetic resonance imaging in a single nanoplatform. Herein, we developed bioinspired coordination-cross-linked amphiphilic polymeric micelles loaded with a model anticancer agent, doxorubicin (Dox). The nanoscale micelles could tolerate substantial dilution to a condition below the critical micelle concentration (9.4 ± 0.3 μg/mL) without sacrificing the nanocarrier integrity due to the catechol-Fe3+ coordinated core cross-linking. Under acidic conditions (pH 5.0), the release rate of Dox was significantly faster compared to that at pH 7.4 as a consequence of coordination collapse and particle de-cross-linking. The cell viability study in 4T1 cells showed no toxicity regarding placebo cross-linked micelles. The micelles with improved stability showed a dramatically increased Dox accumulation in tumors and hence the enhanced suppression of tumor growth in a 4T1 tumor-bearing mouse model. The presence of Fe3+ endowed the micelles T1-weighted MRI capability both in vitro and in vivo without the incorporation of traditional toxic paramagnetic contrast agents. The current work presented a simple "three birds with one stone" approach to engineer the robust theranostic nanomedicine platform.