Shell Of Poly Research Articles

Synchronous delivery of hydroxyapatite and connective tissue growth factor derived osteoinductive peptide enhanced osteogenesis

In bone tissue engineering, electrospun fibrous scaffolds can provide excellent mechanical support, extracellular matrix mimicking components, such as 3D spacial fibrous environment for cell growth and controlled release of signaling molecules for osteogenesis. Here, a facile strategy comprising the incorporation of an osteogenic inductive peptide H1, derived from the cysteine knot (CT) domain of connective tissue growth factor (CTGF), in the core of Silk Fibroin (SF) was developed for osteogenic induction, synergistically with co-delivering hydroxyapatite (HA) from the shell of poly(l-lactic acid-co-ε-caprolactone) (PLCL). The core-shell nanofibrous structure was confirmed by transmission electron microscopy (TEM). Furthermore, the sustained released H1 has effectively promoted proliferation and osteoblastic differentiation of human induced pluripotent stem cells-derived mesenchymal stem cells (hiPS-MSCs). Moreover, after 8 weeks implantation in mice, this SF-H1/PLCL-HA composite induced bone tissue formation significantly faster than SF/PLCL as indicated by μCT. The present study is the first to demonstrate that release of short hydrophilic peptides derived from CTGF combined with HA potentiated the regenerative capacity for healing critical sized calvarial defect in vivo.

Selol nanocapsules with a poly(methyl vinyl ether-co-maleic anhydride) shell conjugated to doxorubicin for combinatorial chemotherapy against murine breast adenocarcinoma in vivo

Nanocapsules containing selol and doxorubicin (NCS-DOX) with an oily core of selol and a shell of poly(methyl vinyl ether-co-maleic anhydride) covalently conjugated to doxorubicin were developed in a previous work. In this study, these nanocapsules showed a similar antitumour effect in comparison to the free doxorubicin (DOX) treatment, but showed no evident DOX-related cardiotoxicity, as evidenced by serum creatine kinase-MB (CK-MB) activity. The histopathological analysis showed that the free DOX treatment induced more intense morphological damage to myocardial tissues in comparison to NCS-DOX treatment. Animals treated with free DOX presented important muscle fibre degradation and animals treated with NCS-DOX, heart tissue did not present signals of muscle fibre degeneration. These results indicate that the cardiotoxicity related to DOX is reduced when this drug is carried by the NCS-DOX. Noteworthy, biodistribution analyses showed that NCS-DOX accumulated more intensely in tumours than the free DOX. Thus, this study reinforces the importance of the development of nanocapsules as drug carriers for the treatment of cancer.

Core–shell PVA/gelatin nanofibrous scaffolds using co‐solvent, aqueous electrospinning: Toward a green approach

ABSTRACTElectrospinning (ES) of gelatin often requires cytotoxic organic solvents or acidic environments, which deteriorate cell recognition sites. In this study, aqueous, non‐toxic, co‐solvent ES was performed to obtain core–shell poly(vinyl alcohol) (PVA)/gelatin nanofiber scaffolds. Effects of the core/shell feed rate ratio (FRR) were investigated on a morphological and mechanical basis. PVA:gelatin ratio of 1:4 was the limiting ratio for specific voltage and electrode distance parameters to obtain uniform fibers. Core–shell bead‐free structures were obtained at 8% PVA and gelatin aqueous solutions. A mean diameter of 280 nm was obtained for 1:1 FRR at 15 kV and 15 cm of electrode distance. Crosslinking resulted in slight improvement in tensile strengths and severe decrease in ductility. Fourier transform infrared spectra revealed retention and improvement of stable secondary structures of gelatin after ES. The scaffolds almost degraded more than 60% in 14 days. Based on the results, present scaffolds hold great promise as suitable candidates for biomedical applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46582.

Polymer fibers with magnetic core decorated with titanium dioxide prospective for photocatalytic water treatment

The present study is focused on the fabrication of magnetic poly(3-hydroxybutyrate)-based core–shell fibers decorated with titanium dioxide (TiO2) as an original and simple approach for the development of novel and effective recyclable hybrid materials designed for purification of waters from organic pollutants. For the first time that was achieved successfully in one-step by simultaneous coaxial electrospinning and electrospraying. Coaxial electrospinning resulted in fabrication of fibers with a core of Fe3O4 nanoparticles in poly(vinyl alcohol) and a shell of poly(3-hydroxybutyrate) and poly(ε-caprolactone). Simultaneously, the surface of electrospun core–shell fibers was purposely decorated with TiO2 nanoparticles by electrospraying of an aqueous dispersion of nano-sized TiO2. The core–shell structure was evidenced by transmission electron and fluorescence microscopies. It was found that this structure and the presence of the inorganic components had an impact on the thermal properties and the crystallinity of the novel hybrid fibrous materials. Moreover, the prepared materials displayed magnetic properties and enhanced tensile strength. Furthermore, the targeted decoration of TiO2 nanoparticles provided excellent photocatalytic activity of the materials under UV light irradiation even after threefold use.

Fabrication of core–shell PLGA/PLA–pNIPAM nanocomposites for improved entrapment and release kinetics of antihypertensive drugs

Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) are two commonly applied biodegradable polymers for the preparation of nanocomposites used in drug-delivery systems. However, these polymers lack desirable attributes such as resistance to aggregation during long-term storage due to lyophilisation. To improve their efficacy, in this work, PLA and PLGA were encapsulated within a shell of poly(N-isopropylacrylamide) (pNIPAM) using a single emulsion technique followed by an aqueous free radical precipitation polymerisation process, yielding core–shell PLA/PLGA–pNIPAM nanocomposites. The nanocomposites were characterised using zeta potential, dynamic light scattering, and transmission electron microscopy analyses and were further applied as a delivery system for ramipril, an antihypertensive drug. The drug-loaded PLGA–pNIPAM core–shell nanoparticles exhibited a higher drug content (91%) and entrapment efficiency (78%) than their PLA counterparts. An in vitro release study of the formulations at pH 7.3 in phosphate-buffered saline indicated that PLGA was more efficient than PLA with a sustained release of 86% of ramipril from the polymer matrix within 24h. Furthermore, to determine the release kinetics, the data were fitted to Korsmeyer–Peppas and Higuchi models; the release of ramipril from the polymer matrix followed zero-order rate kinetics and an anomalous (non-Fickian) diffusion mechanism.

Caveolae-mediated mesenchymal stem cell labelling by PSS-coated PLGA PFOB nano-contrast agent for MRI.

Rationale: Non-invasive tracking of transplanted cells is critical in evaluating delivery, migration and prognosis of cell therapies.Methods: We formulated a nano-contrast agent consisting of a perfluorooctylbromide (PFOB) core within a shell of poly (lactic-co-glycolic acid) (PLGA) followed by a coat of polystyrene sulfonate (PSS) for 19F MRI. The nano-contrast agent (PSS-NP) was characterised by DLS and the uptake efficiency of the nano-contrast agent (PSS-NP) was tested using flow cytometry, in vitro MRI and confocal microscopy. In vitro and in vivo assays of labelled cells were tested for their ability to provide an MRI signal while retaining their osteoblastic differentiation capabilities.Results: PSS-NPs were internalised via caveolae-mediated endocytosis in mesenchymal stromal/stem cells without affecting cell proliferation and differentiation in osteoblasts, both in vitro and in vivo. Furthermore, labelled cells were monitored by 19F MRI for up to 2 months after transplantation in mice. In particular, PSS-NP-labelled cells can be used to monitor the enhanced immune rejection of grafted human cells in normal BALB/c mice compared to immune-compromised NOD/SCID mice. One week after transplantation, 40% of the 19F MRI signal was lost in normal mice, whereas only 10% was lost in immune-compromised mice.Conclusion: Overall, these results show that PSS-NPs can label MSCs effectively, and be employed in vivo as a novel nano-contrast agent for non-invasive cell tracking using clinically relevant 19F MRI techniques.

Nanocapsules for the co-delivery of selol and doxorubicin to breast adenocarcinoma 4T1 cells in vitro

Nanocapsules (NCS-DOX) with an oily core of selol and a shell of poly(methyl vinyl ether-co-maleic anhydride) covalently conjugated to doxorubicin were developed. These nanocapsules are spherical, with an average hydrodynamic diameter of about 170 nm, and with negative zeta potential. NCS-DOX effectively co-delivered the selol and the doxorubicin into 4T1 cells and changed the intracellular distribution of DOX from the nuclei to the mitochondria. Moreover, a significantly increased cytotoxicity against 4T1 cells was observed, which is suggestive of additive or synergic effect of selol and doxorubicin. In conclusion, PVM/MA nanocapsules are suitable platforms to co-deliver drugs into cancer cells.

Development and characterization of cores–shell poly(lactide-co-glycolide)-chitosan microparticles for sustained release of GDNF

The microencapsulation of bioactive neurotrophic factors in biodegradable poly(lactide-co-glycolide) (PLGA) microspheres has been a promising tool in the treatment of various nervous system disorders. However, challenges still exist; the PLGA burst drug release and acidic degradation products often limit clinical application. In this study, cores–shell PLGA-chitosan microparticles (MPs) were fabricated with a single shell of chitosan and multi-cores of PLGA using a re-emulsification method. The glial cell line-derived neurotrophic factor (GDNF) was encapsulated at the PLGA cores of the cores–shell MPs. The cores–shell MPs prepared by different chitosan concentrations showed a rough surface, and the particle mean size varied between 32.3 and 45.2μm. The fluorescence images indicated that Nile red-stained PLGA microspheres were uniformly distributed in the cores–shell MPs. Compared with PLGA microspheres, the cores–shell MPs were able to reduce the initial burst release of GDNF and neutralize the acidity of PLGA degradation products, which could be modulated by changing the chitosan concentrations. Further differentiation of PC12 cells toward a neuronal phenotype in vitro indicated that the cores–shell MPs were capable of maintaining the bioactivity of GDNF during preparation. Taken together, these findings highlight the possibility of using cores–shell PLGA-chitosan MPs for the sustained release of GDNF, which offers potential applications in nerve injury repair.

Superparamagnetic POT/Fe3O4 nanoparticle composites with supported Au nanoparticles as recyclable high-performance nanocatalysts

A novel method has been developed to successfully synthesize Fe3O4 nanoparticles with tunable size and morphology supported on shells of poly(o-Toluidine)(POT) hollow microspheres. The as-prepared POT/Fe3O4 nanoparticle composites can be used as novel and magnetic-responsive catalyst supports to produce highly efficient and recyclable noble metal catalysts. The size of Fe3O4 nanoparticles supported on shells of POT hollow microspheres can be tuned from 4 to 12 nm by changing the concentration of Fe ions. The roles of the doping acid of POT and Zeta potentials of Fe3O4 nanoparticles and POT in the formation of the POT/Fe3O4 nanoparticle composites were discussed. Furthermore, gold nanoparticles that were supported on the as-synthesized POT/Fe3O4 nanoparticle composites have been achieved by utilizing the reactivity of POT towards Au ions. The size of gold nanoparticles can be tuned by altering the concentration of HAuCl4. Finally, the catalytic activity of the obtained POT/Fe3O4/Au composites for 4-nitrophenol (4NP) reduction is investigated. The results demonstrate that such magnetic-responsive polymer-supported gold nanoparticles can be easily recovered and reused five times still remains high catalytic performance, which indicate their potential applications in the field of catalysis.

Multifunctional magnetic co-delivery system coated with polymer mPEG-PLL-FA for nasopharyngeal cancer targeted therapy and MR imaging.

The gene and drug co-delivery system has become one of the primary strategies to overcome cancers. Here, we designed a multifunctional magnetic co-delivery system for nasopharyngeal carcinoma-targeted therapy and MR imaging. Aldehyde sodium alginate (ASA) was used to decorate the oxide iron and load cisplain through coordinate bond to form a core complex. The polymer shell poly(l-lysine)-methoxy-polyethylene glycol-folate was used to coat the core complex through electric interaction to give this nano-medicine a target ability. And this polymer could also give the nano-medicine abilities to adhere and protect DNA, and enhance its solubleness in water. After being transfected with this nano-medicine, the plasmids which contain cancer suppressor gene TFPI2 could enter and express in HNE-1 cells. It caused a higher death and apoptosis rate, inhibited nasopharyngeal carcinoma cells' migration and cloning by the synergic effect together with cisplain. Besides, clear images of this nano-medicine could be got under T2 MR imaging. This magnetic co-delivery system demonstrates a potential as a powerful multifunctional vector for drug delivery and gene vector applications in nasopharyngeal carcinoma.

Coaxial nanofibers from poly(caprolactone)/ poly(vinyl alcohol)/Thyme and their antibacterial properties

Today, with substantial global demand from patients suffering from wounds and burns, the wound care sector has gained great deal of interest in medical industry. Herein, coaxial electrospun poly(caprolactone)/poly(vinyl alcohol) core–shell nanofibers incorporated with Thyme extract in the core structure were prepared using coaxial electrospinning, and the effect of various operational parameters such as polymer concentration, applied voltage, flow rate, distance, and Thyme concentration on nanofiber diameter were studied. Physical and mechanical properties of the nanofibers were determined by analytical techniques. The results revealed that desired nanofibers with uniform surface morphology and acceptable tensile strength could be obtained at applied voltage of 15 kV, needle tip-target of 13 cm, core flow rate of 0.2 mL/h, and shell flow rate of l mL/h. Moreover, MTT assay shows that the nanofibers are highly biocompatible regardless of Thyme encapsulation. Antibacterial activities of the prepared core–shell nanofibers were also examined against two bacteria—gram-positive Staphylococcus and gram-negative Escherichia. Encapsulation of 5% (w/v) Thyme extract concentration in the core–shell poly(caprolactone)/poly(vinyl alcohol) nanofibers led to high antibacterial activity of the produced nanofibers.

PEGylated Cationic Serum Albumin for Boosting Retroviral Gene Transfer.

Retroviral vectors are common tools for introducing genes into the genome of a cell. However, low transduction rates are a major limitation in retroviral gene transfer, especially in clinical applications. We generated cationic human serum albumin (cHSA) protected by a shell of poly(ethylene glycol) (PEG); this significantly enhanced retroviral gene transduction with potentially attractive pharmacokinetics and low immunogenicity. By screening a panel of chemically optimized HSA compounds, we identified a very potent enhancer that boosted the transduction rates of viral vectors. Confocal microscopy revealed a drastically increased number of viral particles attached to the surfaces of target cells. In accordance with the positive net charge of cationic and PEGylated HSA, this suggests a mechanism of action in which the repulsion of the negatively charged cellular and viral vector membranes is neutralized, thereby promoting attachment and ultimately transduction. Importantly, the transduction-enhancing PEGylated HSA derivative evaded recognition by HSA-specific antibodies and macrophage activation. Our findings hold great promise for facilitating improved retroviral gene transfer.

Inflammation-mediated drug release using a gas-generating system for treating osteomyelitis

Event Abstract Back to Event Inflammation-mediated drug release using a gas-generating system for treating osteomyelitis Wei-Lin Wan1*, Ming-Fan Chung1*, Yi-Jun Lin1* and Hsing-Wen Sung1, 2* 1 National Tsing Hua University, Department of Chemical Engineering, Taiwan 2 National Tsing Hua University, Institute of Biomedical Engineering, Taiwan In the conventional treatment of osteomyelitis, the penetration of antibiotics into the infected bone is commonly poor. To ensure that the local antibiotic concentration is adequate, this work develops an injectable calcium phosphate (CP) cement in which is embedded pH-responsive hollow microspheres (HMs) that can control the release of a drug according to the local pH. The HMs are fabricated using a microfluidic device, with a shell of poly(D,L-lactic-co-glycolic acid) (PLGA) and an aqueous core that contains vancomycin (Van) and NaHCO3. At neutral pH, the CP/HM cement elutes a negligible concentration of the drug. In an acidic environment, the NaHCO3 that is encapsulated in the HMs reacts with the acid rapidly to generate CO2 bubbles, disrupting the PLGA shells and thereby releasing Van locally in excess of a therapeutic threshold. The feasibility of using this CP/HM cement to treat osteomyelitis is studied using a rabbit model. Analytical results reveal that the CP/HM cement provides highly effective local antibacterial activity. Histological examination further verifies the efficacy of the treatment by the CP/HM cement. The above findings suggest that the CP/HM cement is a highly efficient system for the local delivery of antibiotics in the treatment of osteomyelitis. Keywords: in vivo, Drug delivery, stimuli-response, Biodegradable material Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials for therapeutic delivery Citation: Wan W, Chung M, Lin Y and Sung H (2016). Inflammation-mediated drug release using a gas-generating system for treating osteomyelitis. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01352 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Wei-Lin Wan, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email1 Dr. Ming-Fan Chung, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, gary940638@gmail.com Dr. Yi-Jun Lin, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email2 Dr. Hsing-Wen Sung, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, hwsung@mx.nthu.edu.tw Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Wei-Lin Wan Ming-Fan Chung Yi-Jun Lin Hsing-Wen Sung Google Wei-Lin Wan Ming-Fan Chung Yi-Jun Lin Hsing-Wen Sung Google Scholar Wei-Lin Wan Ming-Fan Chung Yi-Jun Lin Hsing-Wen Sung PubMed Wei-Lin Wan Ming-Fan Chung Yi-Jun Lin Hsing-Wen Sung Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug.

In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system.

Photovoltaic Properties of CdSe/CdS and CdS/CdSe Core–Shell Particles Synthesized by Use of Uninterrupted Precipitation Procedures

Cadmium Selenide (CdSe) and cadmium sulfide (CdS) are good electron acceptors for hybrid solar cells. CdSe and CdS nanoparticles can be prepared at low temperatures (60–80°C) from alkaline aqueous solutions of a cadmium salt, sodium citrate, and thiourea, as sulfur source, or sodium selenosulfate, as selenium source. Under the same experimental conditions, the reaction kinetics for CdS were faster than for CdSe. Formation of CdSe/CdS core–shell particles (type I: CdSe as core and CdS as shell) could be achieved by use of an uninterrupted one-step process by setting high and low solution temperatures for the core and shell compounds, respectively. The yield of the CdSe product was higher at a pH 8.5–9.5 whereas that of the CdS product was higher at higher pH (10–11). Therefore, formation of the “inverse” CdS/CdSe structure (type II: CdS as core and CdSe as shell) was possible in a one-step solution process by choosing a high solution pH for the core and a lower pH for the shell. Photoluminescence spectra and electron micrographs confirmed formation of the two types of core–shell particle. The photovoltaic performance of heterojunctions prepared with core–shell particles and poly(3-hexylthiophene) (P3HT), also suggested formation of core–shell particles. Both the photovoltage and photocurrent density of hybrid solar cells depended on the shell compound and not on the core. It was shown that the interface of the heterojunctions plays is important in solar cell applications, and its modification could be realized by incorporating different shell compounds on core particles.

A rapid drug release system with a NIR light-activated molecular switch for dual-modality photothermal/antibiotic treatments of subcutaneous abscesses

Eradicating subcutaneous bacterial infections remains a significant challenge. This work reports an injectable system of hollow microspheres (HMs) that can rapidly produce localized heat activated by near-infrared (NIR) light and control the release of an antibiotic via a “molecular switch” in their polymer shells, as a combination strategy for treating subcutaneous abscesses. The HMs have a shell of poly(d,l-lactic-co-glycolic acid) (PLGA) and an aqueous core that is comprised of vancomycin (Van) and polypyrrole nanoparticles (PPy NPs), which are photothermal agents. Experimental results demonstrate that the micro-HMs ensure efficiently the spatial stabilization of their encapsulated Van and PPy NPs at the injection site in mice with subcutaneous abscesses. Without NIR irradiation, the HMs elute a negligible drug concentration, but release substantially more when exposed to NIR light, suggesting that this system is suitable as a photothermally-responsive drug delivery system. The combination of photothermally-induced hyperthermia and antibiotic therapy with HMs increases cytotoxicity for bacteria in abscesses, to an extent that is greater than the sum of the two treatments alone, demonstrating a synergistic effect. This treatment platform may find other clinical applications, especially for localized hyperthermia-based cancer therapy.

A novel route to the preparation of polymer hollow particles decorated with gold nanoparticles in the shell

A novel route was briefly demonstrated to the preparation of polymer hollow particles decorated with gold nanoparticles (AuNPs) in the shell. Polyvinylpyrrolidone, which has reducibility in the formation of noble metallic nanostructures, was first introduced into the shell of poly(ethyleneglycol dimethacrylate-co-methacrylic acid) hollow particles. Numerous AuNPs were then exclusively generated within the polymer shell by the in situ reduction of gold precursor without any external reducing agent. The AuNPs in the resultant hybrid hollow particles were well sequestered from each other and were ca. 5–20 nm in diameter.

Targeted decationized polyplexes for siRNA delivery.

The applicability of small interfering RNA (siRNA) in future therapies depends on the availability of safe and efficient carrier systems. Ideally, siRNA delivery requires a system that is stable in the circulation but upon specific uptake into target cells can rapidly release its cargo into the cytoplasm. Previously, we evaluated a novel generation of carrier systems ("decationized" polyplexes) for DNA delivery, and it was shown that folate targeted decationized polyplexes had an excellent safety profile and showed intracellular triggered release upon cell specific uptake. Targeted decationized polyplexes consist of a core of disulfide cross-linked poly(hydroxypropyl methacrylamide) (pHPMA) stably entrapping nucleic acids and a shell of poly(ethylene glycol) (PEG) decorated with folate molecules. In the present study, the applicability of folate targeted decationized polyplexes for siRNA delivery was investigated. This required optimization of the carrier system particularly regarding the cross-linking density of the core of the polyplexes. Stable and nanosized siRNA decationized polyplexes were successfully prepared by optimizing the cross-link density of their core. Upon incubation in human plasma, a significant portion of siRNA remained entrapped in the decationized polyplexes as determined by fluorescence correlation spectroscopy (FCS). When tested in a folate receptor overexpressing cell line stably expressing luciferase, Skov3-luc, sequence specific gene silencing was observed. As expected, neither interference on the intrinsic luciferase expression nor on the cell metabolic activity (determined by XTT) was induced by the free-polymer or the siRNA polyplexes. In conclusion, targeted decationized polyplexes are safe and stable carriers that interact with the targeted cells and rapidly disassemble upon cell entry making them promising siRNA delivery systems.

A hyperbranched polyester as antinucleating agent for Artemisinin in electrospun nanofibers

The paper deals with the development of an antinucleating strategy to prevent the crystallization of Artemisinin (ART), a potent natural antimalarial agent, through its encapsulation into core–shell nanofibers, constituted by a core of ART blended with a hyperbranched poly(butylene adipate) (HB), covered with a shell of poly(vinyl pyrrolidone) (PVP). The highly branched polymer acted as an effective antinucleating agent. Scanning and transmission electron microscopy analyses evidenced the regular and homogenous morphology of the core–shell electrospun nanofibers. Attenuated total reflectance spectroscopy, differential scanning calorimetry and X-ray diffraction analysis were utilized to assess the activity and the physical state of ART into the nanofibers. It was demonstrated that ART was successfully encapsulated in electrospun nanofibers and could efficiently retain its amorphous state.

Decationized polyplexes as stable and safe carrier systems for improved biodistribution in systemic gene therapy

Many polycation-based gene delivery vectors show high transfection in vitro, but their cationic nature generally leads to significant toxicity and poor in vivo performance which significantly hampers their clinical applicability. Unlike conventional polycation-based systems, decationized polyplexes are based on hydrophilic and neutral polymers. They are obtained by a 3-step process: charge-driven condensation followed by disulfide crosslinking stabilization and finally polyplex decationization. They consist of a disulfide-crosslinked poly(hydroxypropyl methacrylamide) (pHPMA) core stably entrapping plasmid DNA (pDNA), surrounded by a shell of poly(ethylene glycol) (PEG). In the present paper the applicability of decationized polyplexes for systemic administration was evaluated. Cy5-labeled decationized polyplexes were evaluated for stability in plasma by fluorescence single particle tracking (fSPT), which technique showed stable size distribution for 48h unlike its cationic counterpart. Upon the incubation of the polymers used for the formation of polyplexes with HUVEC cells, MTT assay showed excellent cytocompatibility of the neutral polymers. The safety was further demonstrated by a remarkable low teratogenicity and mortality activity of the polymers in a zebrafish assay, in great contrast with their cationic counterpart. Near infrared (NIR) dye-labeled polyplexes were evaluated for biodistribution and tumor accumulation by noninvasive optical imaging when administered systemically in tumor bearing mice. Decationized polyplexes exhibited an increased circulation time and higher tumor accumulation, when compared to their cationic precursors. Histology of tumors sections showed that decationized polyplexes induced reporter transgene expression in vivo. In conclusion, decationized polyplexes are a platform for safer polymeric vectors with improved biodistribution properties when systemically administered.