Drug Loading Behavior Research Articles

Changing the daily injection of glatiramer acetate to a monthly long acting product through designing polyester-based polymeric microspheres.

Introduction: Glatiramer acetate (GA) is a newly emerged therapeutic peptide to reduce the frequency of relapses in multiple sclerosis (MS). Despite its good performance in controlling MS, it is not widely used due to daily or biweekly subcutaneous injections due to rapid degradation and body clearance. Therefore, implant design with sustained release leads to prolonged biological effects by gradually increasing drug exposure and protecting GA from rapid local degradation. Methods: Different emulsion methods, PLGA type, surfactant concentration, drug/polymer ratio, drying processes, stirring method, and other variables in preliminary studies modified the final formulation. The release kinetics were studied through mechanistic kinetic models such as zero-order, Weibull, Higuchi, etc. In this study, all challenges for easy scale-up, methodological detail, and a simple, feasible setup in mass production were discussed. Results: The optimized formulation was obtained by 1:6 drug/PLGA, 0.5% w/w polyvinyl alcohol, and 0.75% w/w NaCl in the external aqueous phase, 1:10 continuous phase to dispersed phase ratio, and without any surfactant in the primary emulsion. The final freeze-dried particles presented a narrow distributed size of 1-10 µm with 7.29% ± 0.51 drug loading and zero-order release behavior with appropriate regression correlation (R2 98.7), complete release, and only 7.1% initial burst release. Conclusion: Therefore, to achieve improvement in patient compliance through better and longer efficacy, designing the parenteral sustained release microspheres (MPSs) of this immune modulator is a promising approach that should be considered.

Modeling the effect of physical crosslinking degree of pH and temperature responsive poly(NIPAAm-co-VSA)/alginate IPN hydrogels on drug release behavior

There is a growing demand to design and development of hydrogel based stimuli responsive drug-delivery systems due to possess several advantages, namely high drug loading capacity, target specific delivery, biocompatibility, reduced drug toxicity and controlled drug release. Because their drug release behavior is dependent on many factors, it is very difficult to accurately characterize these behaviors. So, the characterization of drug loading and release behaviors is very important from an industrial and academic point of view. In this study, pH and temperature responsive poly(NIPAAm-co-VSA)/Alginate interpenetrating polymer network (IPN) hydrogel was synthesized by free radical polymerization in the presence of Poly(NIPA-co-VSA) nano gels. Na-Alginate natural polymer was used to physically cross-link the hydrogels with the Ca2+ ions. To obtain physically crosslinked hydrogel series at different rates, hydrogels were kept in various concentrations of CaCl2 solutions. The mechanical, chemical and morphological properties of obtained hydrogel series were characterized by compression test, FT-IR and SEM analysis techniques. As a result of the mechanical tests, it was determined that the fracture strengths varied between 137 and 830 kPa. The doxorubicin (DOX) loading capacities of the hydrogels were determined to be between 86 and 161 mg DOX/g polymer by the solution impregnation method. Their DOX release behavior have been investigated as a function of time, pH, temperature and physical crosslinking degree of hydrogel. Experimentally obtained and highly complex DOX release behaviors were successfully modeled with the artificial neural network (ANN) technique.

Investigation of Gentamicin Release from Polydopamine Nanoparticles

Polydopamine (PDA), being highly reactive in nature, has acquired great attention in multi-disciplinary fields. Owing to its fascinating properties, including its biocompatible, non-toxic and readily bio-degradative nature, we investigated the drug loading and release behavior, using an aminoglycoside antibiotic gentamicin (G) as a model drug. The gentamicin was loaded into the PDA nanoparticles (NPs) via an in situ polymerization method. The release kinetics of the gentamicin was then studied in pH 3, 5 and 7.4. Two batches with varied gentamicin loadings, G-PDA NPs 1:1 (with approx. 84.1% loaded gentamicin) and G-PDA NPs 0.6:1 (with approx. 72.7% loaded gentamicin), were studied. The drug release data were analyzed by LC–MS. The PDA showed good stability in terms of gentamicin release at alkaline pH over a period of seven days. The negative surface charge of PDA at pH 7.4 makes a strong bond with gentamicin, hence preventing its release from the PDA NPs. However, at pH 5 and 3, the amine groups of PDA are more prone towards protonation, making PDA positively charged, hence the repulsive forces caused the gentamicin to detach and release from the G-PDA NPs. Consequently, approx. 40% and 55% drug release were observed at pH 5 and 3, respectively, from the G-PDA NPs 1:1. However, the drug released from G-PDA NPs 0.6:1 was found to be one half as compared to the G-PDA NPs 1:1, which is obvious to the concentration gradient. These findings suggested that the in situ loading method for gentamicin could provide drug release over a period of seven days, hence defending the drug’s efficacy and safety challenges. Furthermore, two kinetic models, namely the Ritger–Peppas and Higuchi models, were implemented to determine the drug release kinetics. Curve fitting analysis supported our findings for the drug release kinetics which are followed by PDA structural changes in response to pH.

Dendritic-Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery.

Polymers constitute a diverse class of macromolecules that have demonstrated their unique advantages to be utilized for drug or gene delivery applications. In particular, polymers with a highly ordered, hyperbranched structure─"dendrons"─offer significant benefits to the design of such nanomedicines. The incorporation of dendrons into block copolymer micelles can endow various unique properties that are not typically observed from linear polymer counterparts. Specifically, the dendritic structure induces the conical shape of unimers that form micelles, thereby improving the thermodynamic stability and achieving a low critical micelle concentration (CMC). Furthermore, through a high density of highly ordered functional groups, dendrons can enhance gene complexation, drug loading, and stimuli-responsive behavior. In addition, outward-branching dendrons can support a high density of nonfouling polymers, such as poly(ethylene glycol), for serum stability and variable densities of multifunctional groups for multivalent cellular targeting and interactions. In this paper, we review the design considerations for dendron-lipid nanoparticles and dendron micelles formed from amphiphilic block copolymers intended for gene transfection and cancer drug delivery applications. These technologies are early in preclinical development and, as with other nanomedicines, face many obstacles on the way to clinical adoption. Nevertheless, the utility of dendron micelles for drug delivery remains relatively underexplored, and we believe there are significant and dramatic advancements to be made in tumor targeting with these platforms.

Poly(lactic acid-co-glycolic acid)-based celecoxib extended-release microspheres for the local treatment of traumatic heterotopic ossification.

Traumatic heterotopic ossification (THO) is a serious and common clinical post-traumatic complication for which there is no effective and safe drug treatment. Routine administration of nonsteroidal anti-inflammatory drugs (NSAIDs) after injury is extensively used approach for THO. However, serious adverse events can occur in the event of an overdose of NSAIDs. In our study, we have developed a poly(lactic acid-co-glycolic acid) (PLGA) microsphere by emulsifying solvent volatilization for the prolonged slow delivery of celecoxib (CLX). Three groups of celecoxib-poly(lactic acid-co-glycolic acid) microspheres (CLX-PLGA MPs) were prepared with particle sizes of 3.75±1.28μm, 49.56±17.15μm, and 94.98±42.53μm. Meanwhile, related parameters of microspheres in each group were studied: drug loading (DL), encapsulation rate (EE), and slow-release behavior. The DL and EE of the 3 CLX-PLGA MPs did not vary significantly, and subsequently, we selected the second drug loading microspheres with a retardation period of about 70 days for subsequent experiments. Moreover, cellular and animal experiments suggest that the microspheres are biocompatible and can be safely applied to localized trauma tissue. Finally, it is demonstrated that CLX-PLGA MPs have an effect on inhibiting the osteogenic differentiation of bone marrow mesenchymal stem cells and have the potential to inhibit ectopic bone formation of the THO model in Sprague-Dawley rat. Therefore, this study suggests that CLX-PLGA MPs are expected to be applied topically in the early post-traumatic period to prevent the development of THO.

Modulating the Properties of Poly(glycerol sebacate)-Based Polyurethane Hydrogels Using an Organoclay.

Elastomeric hydrogels are promising in soft tissue applications due to their biomimetic mechanical and physical behaviors. In this study, we design and synthesize a poly(glycerol sebacate)-based polyurethane-clay nanocomposite hydrogel system with controllable mechanical, swelling, drug release, and biodegradation behaviors. The polymer-clay nanocomposites are synthesized by in situ polymerization in the presence of a solvent, which facilitates the dispersion of clay within the polymer matrix and their bonding. The nanocomposite hydrogels exhibit higher water swelling ratios in comparison to the neat polymer. The fully swollen hydrogels are capable of enduring complex mechanical deformations such as stretching and knotting, while the tensile moduli of the hydrogels mimic various soft tissues in human body. The mechanical behavior of hydrogels is significantly enhanced by the addition of no more than 3 phr clay, showing higher stiffness, strength, ductility, and toughness. The drug loading and release behavior of the hydrogels is investigated with three model drugs, showing selective drug loading capacity and sustained release, based on the Coulombic interaction between the clay and drug molecules. Biodegradation tests under a simulated body condition reveal a highly tunable degradation rate by the clay content in the nanocomposite hydrogels. Good cytocompatibility by the cell metabolic assay with mouse fibroblasts in vitro is also demonstrated. Finally, three-dimensional microporous foam is manufactured as a proof-of-concept study.

Combination of chemotherapy and photothermal methods for in vitro ablation of MCF-7 cancer cells using crinkly core–shell structure MoS2/C@SiO2 nanospheres

MoS2/C@SiO2 spheres were successfully synthesized by a one-step hydrothermal method using silica as the template, sodium molybdate as the Mo source and glucose as the carbon precursor. In this paper, the antitumor ability of MoS2/C@SiO2 and C@SiO2 nanospheres was evaluated through the photothermal effect induced by near infrared (NIR) spectroscopy and the drug loading and release behaviors of the model drug doxorubicin (DOX). The photothermal conversion efficiency (η) of MoS2/C@SiO2 of 42.5% was 1.2 times that of C@SiO2 (34.7%), which indicated its significant photothermal effect. The drug loading of MoS2/C@SiO2 of 46.5% was much higher than that of C@SiO2 (12.4%); it was 3.75 times that of C@SiO2. The cumulative drug release of MoS2/C@SiO2 and C@SiO2 under a simulated acidic tumor environment and NIR irradiation was 58.9% and 27.29%, respectively. Moreover, the cell viability assays verified that MoS2/C@SiO2-DOX had excellent antitumor ability under the co-stimulation of endogenous (pH) and exogenous (NIR) compared with C@SiO2-DOX. The experimental results showed that the survival rate of cancer cells in MoS2/C@SiO2-DOX under coordinated treatment was only 19.4%, while that of C@SiO2-DOX was 24.6%.

Surface modification of MCM-41 by chain transfer free radical polymerization and their utilization for intracellular pH-responsive delivery of curcumin

In this paper, a simple method that relied on direct chain transfer free radical polymerization was reported to synthesize MSNs based polymeric composites (named as MCM-41-SH-poly (PEGMA-co-VPA)) using poly (ethylene glycol) monomethyl ether (PEGMA) and 4-vinyl phenylboric acid (VPA) as monomers. The utilization of MCM-41-SH-poly (PEGMA-co-VPA) to load and delivery curcumin (CUR) was also evaluated in detail. The structure, properties, drug loading and release behaviors were evidenced by various characterization techniques. The results from biological studies have shown that CUR can be effectively loaded on MCM-41-SH-poly (PEGMA-co-VPA) with high drug loading rate through formation of borate bond between CUR and VPA. More importantly, resultant drug-loading complexes displayed excellent water dispersibility and CUR could be released from complexes with pH responsiveness. Taken together, we have developed a simple method for surface modification MCM-41 and resultant composites could display improved properties for intracellular controlled drug delivery applications.

Microneedle scleral patch for minimally invasive delivery of triamcinolone to the posterior segment of eye

The delivery of therapeutics to the posterior segment of the eye is achieved by invasive procedures, including intravitreal injections and implants. The topically applied formulations would not permeate through different tissue barriers of the eye to reach the posterior segment. Here, we demonstrate the effectiveness of microneedle scleral patch in delivering the model molecule, triamcinolone acetonide, to the posterior segment of the eye. Microneedle scleral patch (MSP) and microneedle corneal patch (MCP) were fabricated through the micromolding technique using rapidly dissolvable polyvinylpyrrolidone. The patches containing 25 microneedles were characterized for physical and mechanical properties, drug loading and release behavior in vitro and ex vivo porcine eye globe model. The distribution of TA administered using MSP and MCP in different ocular tissues was evaluated in the rabbit eye model. The results showed that microneedles with 545 ± 8 µm length and 279 ± 26 µm width at the base in MSP penetrate the scleral membrane with the application of 0.35 ± 0.06 N force. The needles dissolved within 60 s after insertion in the corneal and scleral tissue. The 5 min application of MSP showed a significantly (p < 0.05) greater TA disposition in the vitreous humor and choroid-retinal complex in excised porcine eye globe compared with MCP and TA nanosuspension eye drops. In rabbit model studies, the TA concentration was greatest in the choroid-retinal complex and sclera after administration through intravitreal injection and MSP, respectively. The TA disposition in the sclera was significantly (p < 0.05) greater after MSP application compared with intravitreal injection and MCP application for up to 24 h. MSP application provided a greater safety score compared with intravitreal injection. In conclusion, MSP can be developed as a minimally invasive drug delivery system to target the posterior segment of the eye.

Active drug loading and release behaviors of fourfold channel flopped‐ferritin variants

AbstractHuman ferritin has been heavily investigated as a protein‐based drug deliver agent, due to its unique hollow cage structure for drug loading and an intrinsic tumor targeting function. However, facile strategies for high‐level drug loading and controlled release have not been established, which hampered the use of ferritin as an in vivo delivery platform. We examined active drug uptake and release patterns of various flopped ferritin variants, which use fourfold channels as a route for drug uptake. A flopped channel pore structure was adjusted by diverse mutations around the helix‐connecting loop of the channel. Active loading and release of anti‐cancer drug doxorubicin for these ferritin variants were quantitatively monitored. Drug‐loading ability and spontaneous release degree were both enhanced by channel flopping and a pore size increase. The results could lay a stepping stone for further understanding of drug loading via fourfold ferritin channels.

Enhancement of Solubility Ibuprofen by Solid Dispersion Technique on Natural Mucilage

In this study generally solid dispersions (SDs) of ibuprofen were prepared by for all intents and purposes melt dispersion technique using natural mucilage of Lemon seed as carrier, which really is quite significant. Physical mixtures (PMs) of ibuprofen literally were also prepared with the same carrier and in the same drug-carrier ratio (1:0.5, 1:1 and 1:1.5) to compare the dissolution profile, which generally is fairly significant. The solid dispersions and kind of physical mixtures for all intents and purposes were investigated for drug loading, saturation solubility and dissolution behavior in a subtle way. Saturation solubility study really actually was basically carried out in phosphate buffer (pH 7.4), 0.1 N HCL solution and distilled water, which kind of literally is quite significant. Solid dispersions for all intents and purposes particularly were mostly really found definitely fairly effective to literally kind of enhance the solubility of ibuprofen significantly in all the media, which actually is quite significant. Dissolution test specifically was mostly carried out in two different media, phosphate buffer (pH 7.4) and 0.1 N HCL. Solid dispersion containing Lemon seed mucilage at the ratio of 1:1.5 (drug: carrier) basically showed faster and sort of definitely higher drug release and basically was specifically really found to for the most part actually be most sort of effective among all the very actually solid dispersions in a generally big way, which kind of is fairly significant. Drug carrier interactions specifically specifically were studied by comparing Fourier definitely mostly Transform generally Infrared Spectroscopy (FT-IR) of particularly solid dispersions with pure drug which essentially revealed that the SDs specifically were kind of really stable in a pretty big way, which is fairly significant. So, fairly very solid dispersion may particularly be an definitely really effective technique to specifically enhance dissolution rate of ibuprofen, which kind of literally is fairly significant in a fairly big way.

Synthesis of charged chitosan nanoparticles as functional biolubricant

Osteoarthritis has been a major disease in recent years, which is mainly related to the breakdown of the lubrication function of the cartilage sliding interface, along with the inflammation of the joint capsule. In this paper, one kind of novel biomimetic nanoparticles (NPs) lubricant, named CS-PS, is synthesized through chemically grafting hydrophilic sulfonic acid (SO3−) groups onto the surface of biocompatible and biodegradable chitosan (CS) NPs. Compared with control CS NPs, the as-synthesized CS-PS NPs exhibits excellent hydration and stability because of negatively charged surface zeta potential, along with extraordinary lubrication performance in water for realizing a super-low friction coefficient (COF) as ∼0.01 at the sliding interface of PDMS elastomer-Ti6Al4V disk. Correspondingly, the CS-PS NPs can also be used as a drug carrier for aspirin, which presents very good drug loading and release behavior in PBS (pH = 7.4). MCS cells culture experiment proves that this kind of novel lubricant is nontoxic and biocompatible, for which may be expected to use as potential articular injective material for the treatment of osteoarthritis.

Biodegradable multifunctional bioactive Eu-Gd-Si-Ca glass nanoplatform for integrative imaging-targeted tumor therapy-recurrence inhibition-tissue repair

• A multifunctional bioactive tumor imaging-targeted therapy-repair nanoplatform was constructed. • The nanoplatform showed targeted tumor imaging and therapy. • The nanoplatform efficiently inhibited tumor recurrence and enhanced tissue regeneration. The postoperative tissue healing of tumor excision, monitoring of remained tumor cells and inhibiting of tumor recurrence are still the great challenge. Herein, we develop a multifunctional biodegradable silicon-based Eu-Gd-Si-Ca bioactive glass nanoplatform (MBSGN) for tumor imaging, inhibiting tumor recurrence and enhancing tumor-impaired tissue regeneration. MBSGN exhibited a branched mesoporous structure (10–20 nm), controlled biodegradation, ultrahigh drug loading (602.52 mg g −1 ) and pH responsive release behavior, special magneto-optical properties and tumor cell-targeted surface. MBSGN possessed excellent biocompatibility and tumor cell-targeted capacity in vitro . MBSGN showed multi-model bioimaging capacity for skin tumor tissue (fluorescence/magnetic resonance/computed tomography imaging). MBSGN could efficiently eliminate the tumor growth, inhibit the local tumor recurrence through in situ removal of residual tumor cells, greatly enhance the full-thickness wound healing and tumor surgery-caused wounds repair. This study offers a reasonable and promising pathway for in situ integration of multi-modal bio-imaging, recurrent melanoma therapy and tissue regeneration.

Microfluidic-based fabrication and characterization of drug-loaded PLGA magnetic microspheres with tunable shell thickness

To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device was fabricated and the biocompatible poly(lactic-co-glycolic acid) (PLGA) magnetic drug-eluting beads transarterial chemoembolization (TACE) microspheres with tunable size and shell thickness were prepared via this device. Paclitaxel, as a model active, was loaded through O/O/W emulsion method with high efficiency. The size and the shell thickness vary when adjusting the flow velocity and/or solution concentration, which caters for different clinical requirements to have different drug loading and release behavior. Under the designed experimental conditions, the average diameter of the microspheres is 60 ± 2 μm and the drug loading efficiency has reached 6%. The drug release behavior of the microspheres shows the combination of delayed release and smoothly sustained release profiles and the release kinetics differ within different shell thickness. The microspheres also own the potential of magnetic resonance imaging (MRI) visuality because of the loaded magnetic nanoparticles. The microsphere preparation method and device we proposed are simple, feasible, and effective, which have a good application prospect.

Efficient Regulation of the Behaviors of Silk Fibroin Hydrogel via Enzyme-Catalyzed Coupling of Hyaluronic Acid.

Pure silk fibroin (SF) hydrogel exhibits poor elasticity and low water retention ability, owing to the compact crystalline structure and high content of hydrophobic amino acids. Herein, a composite double-network hydrogel of SF and tyramine-modified hyaluronic acid (mHA) was constructed, via the laccase-catalyzed coupling reactions between the phenolic hydroxyl groups from SF and mHA chains. The obtained hydrogel exhibits improved structural stability and flexibility compared to pure SF hydrogel. Meanwhile, the swelling ratio, mechanical property, drug loading, and release behaviors can be readily regulated by alcoholization, altering pH value, and ionic strength of soaking solutions. Increasing pH values promoted the swelling capacity of SF/mHA hydrogel, resulting in an efficient loading of cationic drugs and sustained release of anionic drugs as well. The addition of inorganic salts reduced electrostatic repulsion in the hydrogel scaffold, accompanying with a noticeable improvement of toughness. Furthermore, alcohol treatment induced conformation changes of fibroin protein, and the composite hydrogel achieved a higher fracture and improved elasticity. The present work provides a biological alternative to regulate the mechanical behavior, drug loading, and sustained release capacity of the SF-based hydrogel.

Design and Synthesis of Multi-Functional Superparamagnetic Core-Gold Shell Coated with Chitosan and Folate Nanoparticles for Targeted Antitumor Therapy.

A dual-targeting nanomedicine composed of pH-sensitive superparamagnetic iron oxide core-gold shell SPION@Au, chitosan (CS), and folate (FA) was developed as a doxorubicin (DOX) antitumor medication. Microemulsion was used for preparation and cross-linking conjugation. The characteristics of the designed nanocomposite were studied using atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction, UV-visible spectroscopy, Zeta potential and vibrating sample magnetometry (VSM), and Fourier transform infrared spectroscopy. The prepared SPION@Au-CS-DOX-FA nanoparticles (NPs) were spherical with an average diameter of 102.6 ± 7 nm and displayed an elevated drug loading behavior and sustained drug release capacity. The SPION@Au-CS-DOX-FA NPs revealed long term anti-cancer efficacy due to their cytotoxic effect and apoptotic inducing efficiency in SkBr3 cell lines. Additionally, Real-time PCR outcomes significantly showed an increase in BAK and BAX expression and a decrease in BCL-XL and BCL-2. In vivo results revealed that SPION@Au significantly decreased the tumor size in treated mice through magnetization. In conclusion, prepared SPION@Au-CS-DOX-FA could be a beneficial drug formulation for clinical breast cancer treatment.

Microfluidic preparation of PLGA composite microspheres with mesoporous silica nanoparticles for finely manipulated drug release.

The current study explored the feasibility of a microfluidic preparation of PLGA composite microspheres with mesoporous silica nanoparticles (MSNs) to finely manipulate the drug release behaviors of the microspheres. MSNs were synthesized via a hydrothermal method, and PLGA microspheres loaded with MSNs (PLGA-MSNs) were prepared using a capillary-based three-phase microfluidic device. Drug loading and release behaviors using rhodamine B (RB) as a water-soluble model drug were investigated and compared with those of PLGA microspheres. MSNs with an average particle size of 119nm, a specific surface area of 902.5cm2/g, and a pore size of approximately 5nm were obtained. The mean diameter of PLGA-MSNs was 56μm (CV=4.91%). A sustained release duration of encapsulated RB from PLGA-MSNs for 4months was achieved without any observable burst release. PLGA microspheres with monodispersion could also allow for a similar release duration of encapsulated RB but encountered a burst release in the mid-term of the studied duration. PLGA-MSNs had a denser outer PLGA layer and a more centralized hollow hole than PLGA microspheres without MSNs. Hence, the incorporation of MSNs into PLGA microspheres via microfluidics could be an efficient strategy to finely tune the drug release behavior of PLGA microspheres.

Synthesis and characterization of PLGA-PEG-PLGA based thermosensitive polyurethane micelles for potential drug delivery

Polyurethane nanomicelle is a promising functional drug delivery system. In this work, the polyurethane (P3-PU) was synthesized from PLGA1200-PEG1450-PLGA1200 (P3, a thermosensitive and biodegradable triblock copolymer) and L-lysine ester diisocyanate (LDI). Then, reactive benzaldehyde was further imported to terminate P3-PU to obtain benzaldehyde modified polyurethane (P3-PUDA). The micelles, temperature-sensitive P3-PU nanomicelle and P3-PUDA nanomicelle, were systematically investigated, including the size, stability, temperature sensitivity, drug loading and release behavior, cytotoxic on human hepatocytes (L02), and inhibitory effect on human hepatocellular carcinoma cells (HepG2). The results show the thermosensitive behavior of the micelles can be adjusted by the terminal group. The polyurethane micelles with a uniform size between 20 nm and 30 nm showed excellent stability and good biocompatibility to L02 cells. Besides, in vitro experiments showed that Dox-loaded P3-PUDA micelles exhibited faster and higher release rate at 37 °C and better inhibitory effect on HepG2 than the Dox-loaded P3-PU micelles. Moreover, the achieved benzaldehyde modified polyurethanes also provides various possibilities to adjust further to enlarge its applications. Therefore, the polyurethane micelles will have great potential in the field of drug carriers.

Comparison of two nanocarriers for quercetin in morphology, loading behavior, release kinetics and cell inhibitory activity

Recently, nanocarrier loading drugs have caused widespread concern. However, there are few reports about comparison of drug loading behavior of different nanoparticles. In this study, we prepared two nanocarriers (starch nanoparticles and F127 nanoparticles) for oral and intravenous injections, respectively. We used dynamic light scattering and transmission electron microscopy to study the morphology of the nanocarriers. Moreover, the loading behavior of nanoparticles on quercetin (QC) and the release behavior of nanoparticles at different pH levels were studied. In artificial gastric (pH 2.0) and intestinal (pH 6.8) juices, QC showed a sustained release in two nanoparticles. Meanwhile starch nanoparticle-QC and F127-QC nanosystems both showed relatively higher inhibitory activities than free QC on five kinds of cells, especially for cell A549, the cell inhibition ratio achieved to 55.16% and 64.06%, respectively. This study provided a reference for oral and injection of drug-loaded nanoparticles.

Effects of the GluN2B antagonist, Ro 25-6981, on extinction consolidation following adolescent- or adult-onset methamphetamine self-administration in male and female rats.

Previous work suggests adolescent rats have deficient extinction consolidation relative to adults. Although the mechanisms underlying this age difference are currently unknown, studies in adult rats have implicated GluN2B-containing N-methyl-d-aspartate (NMDA) receptor function in extinction consolidation of drug-associated memory. Importantly, GluN2B neurotransmission emerges during adolescent development, and drugs of abuse during adolescence may delay the development of extinction consolidation by disrupting the ontogeny of GluN2B function. Here, we trained Sprague-Dawley rats of both sexes to self-administer methamphetamine [METH, 0.1 mg/kg/infusion intravenous (i.v.)] beginning during adolescence [postnatal (P) day 41] or adulthood (P91). Rats were given short access (2 h) to self-administer METH in seven daily sessions followed by 14 sessions with long access (6 h). Subsequently, rats underwent four daily 30-minute extinction sessions with immediate postsession injections of either a GluN2B antagonist [Ro25-6981; 6 mg/kg, intraperitoneal (i.p.)] or a vehicle solution. After four daily 2-h extinction sessions, a priming injection (1 mg/kg METH, i.p.) was given prior to a final 2-h reinstatement session. During LgA, adolescent-onset rats earn more METH than adult-onset rats and display greater drug-loading behavior. Rats reduced their drug-seeking behavior across the extinction sessions, with no significant group differences. Rats reinstated drug-seeking following the METH-priming injection, with females displaying greater reinstatement than males. These results do not support our a priori hypothesis that adolescent-onset METH use disrupts the ontogeny of GluN2B transmission and contributes to age-of-onset differences in extinction of METH-seeking. However, our findings suggest that age-of-onset contributes to excessive METH-taking, while sex confers vulnerability to relapse to METH-seeking.