Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy

A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy.     

Shear bond strength of an autopolymerizing repair resin to injection-molded thermoplastic denture base resins

Abstract

Objective. This study investigated the shear bond strength of an autopolymerizing repair resin to injection-molded thermoplastic denture base resins. Materials and methods. Four injection-molded thermoplastic resins (two polyamides, a polyethylene terephthalate copolymer and a polycarbonate) were used in this study. The specimens were divided into eight groups according to the type of surface treatment given: (1) no treatment, (2) air abrasion with alumina, (3) dichloromethane, (4) ethyl acetate, (5) 4-META/MMA-TBB resin, (6) alumina and 4-META/MMA-TBB resin, (7) tribochemical silica coating or (8) tribochemical silica coating and 4-META/MMA-TBB resin. Half of the specimens in groups 1, 5, 6 and 8 were thermocycled for 10,000 cycles in water between 5–55°C with a dwell time of 1 min at each temperature. The shear bond strengths were determined. Results. The shear bond strengths to the two polyamides treated with alumina, dichloromethane and ethyl acetate and no treatment were very low. The greatest post-thermocycling bond strengths to polyamides were recorded for the specimens treated with tribochemical silica coating and 4-META/MMA-TBB resin (PA12: 16.4 MPa, PACM12: 17.5 MPa). The greatest post-thermocycling bond strengths to polyethylene terephthalate copolymer and polycarbonate were recorded for the treatment with alumina and 4-META/MMA-TBB resin (22.7 MPa, 20.8 MPa). Conclusion. Polyamide was exceedingly difficult to bond to an autopolymerizing repair resin; the shear bond strength improved using tribochemical silica coating followed by the application of 4-META/MMA-TBB resin. Both polyethylene terephthalate copolymer and polycarbonate were originally easy to bond to an autopolymerizing repair resin. However, with 4-META/MMA-TBB resin, the bond was more secure.     

Effect of Mica Reinforcement on the Flexural Strength and Microhardness of Polymethyl Methacrylate Denture Resin

Purpose : Conventional denture base polymethyl methacrylate (PMMA) is low in strength, soft, and brittle on impact. Improvements in the mechanical properties of denture base materials have been sought by adding different reinforcing phases to the PMMA matrix. The purpose of this work was to study the effects of mica reinforcement on the mechanical properties, flexural strength, and microhardness of PMMA denture base resin. Materials and Methods : Wet ground muscovite mica and Lucitone 199 original shade denture base resin were used. Two micas were tested: W200 and P66 with average particle sizes (d50) of 131 μm and 30 μm, respectively. The mica was silane treated in a solution of 3‐methacryloxypropyl trimethoxysilane, ethanol, and water, and then dried. The specimens were fabricated using the denture base resin manufacturer's instructions with a powder : liquid ratio of 21 g/10 ml and a mixing time of 30 seconds. Five treatment groups were produced with differing amounts of mica added to the PMMA denture base resin: (A) control group with 0 vol% mica, (B) 10 vol% W200 mica, (C) 20 vol% W200 mica, (D) 10 vol% P66 mica, (E) 20 vol% P66 mica. The mica replaced equal volumes of the PMMA powder component to minimize changes in viscosity. The three‐point bending flexural strength specimens were 70 × 11 × 3 mm³. Seven specimens were prepared for each treatment group. The hardness specimens were prepared from the ends of the three‐point bend specimens after they were broken (N = 7). After deflasking, the specimens were polished with 600 grit silicon carbide paper to achieve smooth surfaces. A standard three‐point bending jig with a span length of 50 mm was attached to an Instron universal testing machine. The specimens were placed on the jig, and loading was carried out using a 1 mm/min crosshead speed until failure. Microhardness was measured using a Clark microhardness tester with a Knoop indenter. The load was set to 200 g and the dwell time to 15 seconds. ANOVA and Tukey tests were used for statistical analyses (Alpha = 0.05). Results : The flexural strength of the control group was between 77% and 94% higher than all the mica‐containing groups (p≤ 0.05). No significant differences were found within the four mica groups. Microhardnesses of the 20% mica groups (both fine and coarse) were 33% and 26% higher than the control (p≤ 0.05). The 10% mica groups had higher hardness than the control group, but the increase was not statistically significant (p > 0.05). Conclusion : Mica additions to denture PMMA reduced flexural strength; however, with the specimens containing highest mica concentrations (20%), microhardness significantly increased.     

Characterization of Bone Cements

Thirty-seven patients with fractures of the thoracic and lumbar spine treated with Harrington instrumentation were reviewed. Twenty-seven patients with a follow-up time of more than 2 years were summoned for a clinical and radiographic examination. This report presents the results related to reduction, stabilization, return of neural function, spinal posture and mobility, and residual disability. It is concluded that Harrington instrumentation can be performed without a substantial number of complications. Its major advantages are early mobilization and ambulation. The operative technique is discussed with special reference to the preservation of the normal configuration of the back. The value of computerized tomography in the preoperative assessment is stressed.     

Subclassification and Treatment Results of Ethanol Embolotherapy of Type II Arteriovenous Malformations of the Extremity and Body

PurposeTo evaluate the safety and efficacy of ethanol and coil embolization of type II arteriovenous malformation (AVM) according to a new subtype classification.Materials and MethodsEighty-four type II AVMs in the body or extremity of 79 patients who underwent AVM treatment from 1996 to 2017 were retrospectively subclassified according to the angiographic morphology of the draining vein as type IIa (arterioles shunt to focal segment of single draining vein), type IIb (arterioles shunt to venous sac with multiple draining veins), and type IIc (arterioles shunt along long segment of draining vein). Coil and ethanol embolization of the focal or long segment of the draining vein or the venous sac was performed with direct puncture or transvenous approach according to subtype. Treatment outcomes, number of treatment sessions, and complications were analyzed.ResultsAVM cure (ie, complete embolization) rates were 95%, 76%, and 65% in types IIa, IIb, and IIc AVMs, respectively. The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs (P = .015). Median numbers of treatment sessions were 1 in types IIa and IIb AVMs and 2.5 in type IIc AVMs, with a significant difference between type IIc and the other 2 types (P < .05). Minor complications occurred in 20% of patents and major complications occurred in 7%.ConclusionsThe cure rate of type IIa AVMs was significantly better than that of type IIc AVMs, which also required significantly more treatment sessions than the other 2 types.     

Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release

Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system.     

Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.     

Amphiphilic block copolymer delivery of a DNA vaccine against Zika virus

Zika virus (ZIKV) is a mosquito-borne flavivirus that was first discovered in 1947. Since then, outbreaks have been reported in tropical Africa, Southeast Asia, the Pacific Islands, and, in 2015, in the Americas. Since 2013, many countries have reported cases of microcephaly and other central nervous system malformation associated with ZIKV. Because the initial target population for a ZIKV vaccine is expected to be women of child-bearing age, including those who may be pregnant, it is necessary to develop safe, easily administered, and non-viral vaccines. Here, we show that a single tetrafunctional Amphiphilic Block Copolymer (ABC) delivers DNA that encodes the full natural sequence of prM-E, among other antigen designs tested, induces the highest antibody titer and neutralization activity against three divergent ZIKV isolates. Vaccination with a single tetrafunctional block copolymer delivering low dose (10 µg) DNA plasmid rapidly induces protection from detectable viremia during acute infection in mice challenged by ZIKV more than 7 months after their first vaccination and boosted 2 weeks before challenge. This use of tetrafunctional ABCs is a new approach to deliver DNA antigens against flaviviruses. The data demonstrate that DNA formulated by a tetrafunctional block copolymer rapidly elicits protective responses against multiple diverse ZIKV isolates. This represents potential for an easy-to-administer and simple to manufacture vaccine candidate against ZIKV and possibly other emerging threats to global health.     

Quality of written communication and master impressions for fabrication of removable partial prostheses in the Kingdom of Bahrain

The aim of this study was to examine the quality of written instructions and choice of impression trays and materials for removable partial dentures (RPDs) in the Kingdom of Bahrain. All six private dental laboratories in Bahrain were contacted and invited to participate in the study. Five laboratories participated, and submitted written instructions received by them for fabrication of both acrylic (A-RPDs) and cobalt-chromium (CC-RPDs) RPDs. These were examined for evidence of selected design variables. Types of impression trays and materials used were also recorded. One hundred and thirty-one written instructions were examined. Eleven percent (n = 14) were for CC-RPDs, 89% (n = 117) for A-RPDs. All treatments were provided on a private basis. Fifty-seven percent (n =1 8) of CC-RPD instructions requested the technician to design the prosthesis, 43% (n = 6) contained a diagram and 43% (n = 6) mentioned all design variables. Seventy-nine percent (n = 92) of A-RPDs requested the technician to design the denture, and only 1% (n = 1) mentioned all design variables. Alginate impression material was most commonly used for master impressions (83% of impressions (n = 109); 85% (n = 99) of A-RPDs, and 71% (n = 10) of CC-RPDs). Master casts were poured after a minimum of 24 h. Acrylic custom trays were used in 14% (n = 19) of cases (43% (n = 6) of CC-RPDs; 13% (n = 15) of A-RPDs). The quality of written instructions to dental laboratories for the fabrication of RPDs was found to be inadequate in Kingdom of Bahrain. There was widespread use of inappropriate impression trays and materials.     

Experimental Study of Tensile Properties of Styrene–Butadiene–Styrene Modified Asphalt Binders

The requirements imposed on road pavements are ever increasing nowadays, necessitating the improvement of the properties of paving materials. The most commonly used paving materials include bituminous mixtures that are composed of aggregate grains bound by a bituminous binder. The properties of bitumens can be improved by modification with polymers. Among the copolymers used for modifying bitumens, styrene–butadiene–styrene, a thermoplastic elastomer, is the most commonly used. This article presents the results of tests conducted on bitumens modified with two types of styrene–butadiene–styrene copolymer (linear and radial). Two bitumen types of different penetration grades (35/50 and 160/220) were used in the experiments. The content of styrene–butadiene–styrene added to the bitumen varied between 1% and 6%. The results of the force ductility test showed that cohesion energy can be used for qualitative evaluation of the efficiency of modification of bitumen with styrene–butadiene–styrene copolymer. The determined values of the cohesion energy were subjected to the original analysis taking into account the three characteristic elongation zones of the tested binders. The performed analyses made it possible to find a parameter whose values correlate significantly with the content of styrene–butadiene–styrene copolymer in the modified bitumen. With smaller amounts of added modifier (approximately 2%), slightly better effects were obtained in the case of linear copolymer styrene–butadiene–styrene and for larger amounts of modifier (5–6%) radial copolymer styrene–butadiene–styrene was found to be more effective. This is confirmed by the changes in the binder structure, as indicated by the penetration index (PI).