Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 80
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
3.
Eur J Pharm Biopharm ; 154: 338-347, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32739535

RESUMO

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption.

4.
Nanoscale ; 12(29): 15905, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32729863

RESUMO

Correction for 'Non-reversible heat-induced gelation of a biocompatible Fmoc-hexapeptide in water' by Jonathan P. Wojciechowski et al., Nanoscale, 2020, 12, 8262-8267, DOI: .

5.
Nanomedicine ; 28: 102214, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32360550

RESUMO

In the field of nanomedicine, the development of targeted drug delivery aims to design more effective delivery systems that directly target cancer cells and tumours. The development of transdermal delivery mechanisms is promising. At the same time, these areas of research raise profound social and ethical questions and are tied to significant transformations in the nature of contemporary healthcare and personal subjectivity. Socio- political consideration of these issues is shaped by a wider set of debates concerning the societal dimensions of nanotechnology. In this paper we report findings from an interdisciplinary research project uilising semi-structured interviews with key-informants engaged in cancer research and health-care. We identified narrative constracts that shaped participants' responses to and understandings of novel nanomedicines. This analysis contributes to a growing body of literature on the social and ethical aspects of nanotechnology and nanomedicine, providing evidence for the engagement of publics in the early stage of technological developments.

6.
Soft Matter ; 16(20): 4800-4805, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32400837

RESUMO

Peptide hydrogels show great promise as extracellular matrix mimics due to their tuneable, fibrous nature. Through incorporation of polar cationic, polar anionic or polar neutral amino acids into the Fmoc-diphenylalanine motif, we show that electrostatic charge plays a key role in the properties of the subsequent gelators. Specifically, we show that an inverse relationship exists for biocompatibility in the solution state versus the gel state for cationic and anionic peptides. Finally, we use tethered bilayer lipid membrane (tBLM) experiments to suggest a likely mode of cytotoxicity for tetrapeptides which exhibit cytotoxicity in the solution state.

7.
Adv Healthc Mater ; 9(13): e2000261, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32424998

RESUMO

There is a need for improved nanomaterials to simultaneously target cancer cells and avoid non-specific clearance by phagocytes. An ellipsoidal polymersome system is developed with a unique tunable size and shape property. These particles are functionalized with in-house phage-display cell-targeting peptide to target a medulloblastoma cell line in vitro. Particle association with medulloblastoma cells is modulated by tuning the peptide ligand density on the particles. These polymersomes has low levels of association with primary human blood phagocytes. The stealth properties of the polymersomes are further improved by including the peptide targeting moiety, an effect that is likely driven by the peptide protecting the particles from binding blood plasma proteins. Overall, this ellipsoidal polymersome system provides a promising platform to explore tumor cell targeting in vivo.

8.
Nanoscale ; 12(15): 8262-8267, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32236222

RESUMO

Hydrogel materials which respond to changes in temperature are widely applicable for injectable drug delivery or tissue engineering applications. Here, we report the unsual heat-induced gelation behaviour of a low molecular weight gelator based on an Fmoc-hexapeptide, Fmoc-GFFRGD. We show that Fmoc-GFFRGD forms kinetically stable fibres when mixed with divalent cations (e.g. Ca2+). Gelation of the mixture occurs upon heating of the mixture which enables electrostatic screening by the divalent cations and hydrophobic collapse of the fibres to give a self-supporting hydrogel network that shows good biocompatibility with L929 fibroblast cells. This work highlights a unique mechanism to initiate heat-induced gelation which should find opportunities as a gelation trigger for injectable hydrogels or fundamental self-assembly applications.

9.
J Mater Chem B ; 8(5): 863-877, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31950969

RESUMO

Self-assembling short peptides have attracted widespread interest due to their tuneable, biocompatible nature and have potential applications in energy materials, tissue engineering, sensing and drug delivery. The hierarchical self-assembly of these peptides is highly dependent on the selection of not only amino acid sequence, but also the capping group which is often employed at the N-terminus of the peptide to drive self-assembly. Although the Fmoc (9H-fluorenylmethyloxycarbonyl) group is commonly used due to its utility in solid phase peptide synthesis, many other aromatic capping groups have been reported which yield functional, responsive materials. This review explores recent developments in the utilisation of functional, aromatic capping groups beyond the Fmoc group for the creation of redox-responsive, fluorescent and drug delivering hydrogel scaffolds.

10.
Sci Rep ; 10(1): 770, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964927

RESUMO

In this study, we describe the synthesis and molecular properties of anthranilamide-based short peptides which were synthesised via ring opening of isatoic anhydride in excellent yields. These short peptides were incorporated as low molecular weight gelators (LMWG), bola amphiphile, and C3-symmetric molecules to form hydrogels in low concentrations (0.07-0.30% (w/v)). The critical gel concentration (CGC), viscoelastic properties, secondary structure, and fibre morphology of these short peptides were influenced by the aromaticity of the capping group or by the presence of electronegative substituent (namely fluoro) and hydrophobic substituent (such as methyl) in the short peptides. In addition, the hydrogels showed antibacterial activity against S. aureus 38 and moderate toxicity against HEK cells in vitro.

11.
J Med Chem ; 63(5): 2181-2193, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-31347843

RESUMO

Medulloblastoma is a malignant brain tumor diagnosed in children. Chemotherapy has improved survival rates to approximately 70%; however, children are often left with long-term treatment side effects. New therapies that maintain a high cure rate while reducing off-target toxicity are required. We describe for the first time the use of a bacteriophage-peptide display library to identify heptapeptides that bind to medulloblastoma cells. Two heptapeptides that demonstrated high [E1-3 (1)] or low [E1-7 (2)] medulloblastoma cell binding affinity were synthesized. The potential of the peptides to deliver a therapeutic drug to medulloblastoma cells with specificity was investigated by conjugating E1-3 (1) or E1-7 (2) to doxorubicin (5). Both peptide-drug conjugates were cytotoxic to medulloblastoma cells. E1-3 doxorubicin (3) could permeabilize an in vitro blood-brain barrier and showed a marked reduction in cytotoxicity compared to free doxorubicin (5) in nontumor cells. This study provides proof-of-concept for developing peptide-drug conjugates to inhibit medulloblastoma cell growth while minimizing off-target toxicity.

12.
J Am Chem Soc ; 141(51): 20146-20154, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31789022

RESUMO

The use of geminal di(guanidinium) and acridin-9(10H)-one-derived di(carboxylate) derivatives (1a-c and 2a-e, respectively) allows stabilization of heterodimers characterized by high binding affinities in water (maximum ΔG < -7 kcal mol-1, Ka > 105 M-1) as inferred from UV-vis spectroscopic titrations and ITC measurements, therefore rivaling or surpassing the interaction energy between the strongest DNA or RNA triplet pairs. These duplexes are readily accessible and are structurally modifiable, rendering them attractive as building blocks for creating heteroduplex constructs. Incorporating poly(ethylene glycol)-decorated benzyl groups into the dicarboxylate, allows formation of hydrogels in the case of 1b-2c.

13.
J Am Chem Soc ; 141(49): 19479-19486, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31714761

RESUMO

Dual catalytic light-driven cross-coupling methodologies utilizing a Ni(II) salt with a photocatalyst (PC) have emerged as promising methodologies to forge aryl C-N bonds under mild conditions. The recent discovery that the PC can be omitted and the Ni(II) complex directly photoexcited suggests that the PC may perform energy transfer (EnT) to the Ni(II) complex, a mechanistic possibility that has recently been proposed in other systems across dual Ni photocatalysis. Here, we report the first studies in this field capable of distinguishing EnT from electron transfer (ET), and the results are consistent with Förster-type EnT from the excited state [Ru(bpy)3]Cl2 PC to Ni-amine complexes. The structure and speciation of Ni-amine complexes that are the proposed EnT acceptors were elucidated by crystallography and spectroscopic binding studies. With the acceptors known, quantitative Förster theory was utilized to predict the ratio of quenching rate constants upon changing the PC, enabling selection of an organic phenoxazine PC that proved to be more effective in catalyzing C-N cross-coupling reactions with a diverse selection of amines and aryl halides.

14.
ACS Appl Mater Interfaces ; 11(43): 40372-40381, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31621280

RESUMO

The electrolyte is an essential constituent of the light-emitting electrochemical cell (LEC), since its operating mechanism is dependent on the redistribution of mobile ions in the active layer. Recent developments of new ion transporters have yielded high-performance devices, but knowledge about the interactions between the ionic species and the ion transporters and the influence of these interactions on the LEC performance is lacking. We therefore present a combined computational and experimental effort that demonstrates that the selection of the end group in a star-branched oligomeric ion transporter based on trimethylolpropane ethoxylate has a paramount influence on the ionic interactions in the electrolyte and thereby also on the performance of the corresponding LECs. With hydroxyl end groups, the cation from the salt is strongly coordinated to the ion transporter, which leads to suppression of ion pairing, but the penalty is a hindered ion release and a slow turn-on for the LEC devices. With methoxy end groups, an intermediate coordination strength is seen together with the formation of contact ion pairs, but the LEC performance is very good with fast turn-on. Using a series of ion transporters with alkyl carbonate end groups, the ion transporter:cation coordination strength is lowered further, but the turn-on kinetics are slower than what is seen for devices comprising the methoxy end-capped ion transporter.

15.
Chem Soc Rev ; 48(15): 4019-4035, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31187792

RESUMO

Polymersomes are self-assembled hollow membrane sacs that are not only able to encapsulate hydrophobic and/or hydrophilic molecules, but also possess exceptional chemical and physical stability, structural versatility, and surface modifiability. For the above reasons, polymersomes have in recent years emerged as a powerful tool for a wide range of applications in the fields of biomimicry and drug delivery. The full potential of polymersomes, however, has yet to be harnessed due to a lack of appreciation of existing shape control methods. This very much contrasts the field of inorganic nanoparticle synthesis where non-spherical hollow metal nanoparticles are routinely prepared and used. Here, we summarize recent efforts over the past decade to study the morphological transformation of conventionally spherical polymersomes into non-spherical polymersomes.

16.
Chem Sci ; 10(9): 2725-2731, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30996990

RESUMO

The creation of "soft" deformable hollow polymeric nanoparticles with complex non-spherical shapes via block copolymer self-assembly remains a challenge. In this work, we show that a perylene-bearing block copolymer can self-assemble into polymeric membrane sacs (polymersomes) that not only possess uncommonly faceted polyhedral shapes but are also intrinsically fluorescent. Here, we further reveal for the first time an experimental visualization of the entire polymersome faceting process. We uncover how our polymersomes facet through a sphere-to-polyhedron shape transformation pathway that is driven by perylene aggregation confined within a topologically spherical polymersome shell. Finally, we illustrate the importance in understanding this shape transformation process by demonstrating our ability to controllably isolate different intermediate polymersome morphologies. The findings presented herein should provide opportunities for those who utilize non-spherical polymersomes for drug delivery, nanoreactor or templating applications, and those who are interested in the fundamental aspects of polymersome self-assembly.

17.
Rapid Commun Mass Spectrom ; 33(12): 1076-1083, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30900784

RESUMO

RATIONALE: The decolouration of brilliant blue FCF by the action of titanium dioxide (TiO2 ) under ultraviolet (UV) exposure has been recently reported as the basis of a paper-based sensor for monitoring UV sun exposure. The mechanism of brilliant blue FCF photodegradation in the presence of the photocatalyst and the resulting photoproducts are thus far unknown. METHODS: The UV-initiated photodegradation of brilliant blue FCF in the presence of TiO2 for both the aqueous and the solid state was investigated. Degradation in the solid state was observed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS). Decomposition of the dye in the aqueous state was analyzed using liquid chromatography/mass spectrometry (LC/MS) and ultraviolet-visible (UV-Vis) spectroscopy. RESULTS: After UV radiation exposure, the brilliant blue FCF base peak [M1 + NH4 ]+ (m/z calc. 766.194 found 766.194) decreased in the LC/MS chromatogram with a concomitant appearance of BB-FCF decomposition products involving the sequential loss of the N-ethyl and N-methylbenzene sulfonate (MBSA) groups, assigned as [M2 + H]+ (-MBSA, calc. 579.163 found 579.162), [M3 + H]+ (-MBSA, -Et, calc. 551.131 found 551.131), [M4 + H]+ (-2MBSA, calc. 409.158 found 409.158), [M5 + H]+ (-2MBSA, -Et, calc. 381.127 found 381.127). Ions [M2 + H]+ and [M3 + H]+ were also identified in the photodegradation products using MALDI-MS. Observation by UV-Vis indicated a decrease in the solution absorbance maxima and an associated blue-shift upon UV exposure in solution. CONCLUSIONS: The LC/MS analysis indicated two main oxidation processes. The most obvious was attack of the N-methylene, eliminating either ethyl or MBSA groups. The presence of the hydroxylated decomposition product M13 ([M13 + H]+ , calc. 595.157 found 595.157) supported this assignment. In addition, the detection of photoproduct M8, proposed to be 3-((ethylamino)methyl)benzenesulfonic acid ([M8 + H]+ , calc. 216.069 found 216.069), indicates an aryl-oxidative elimination. The absence of the aryl-hydroxy products normally expected to accompany the formation of M8 is proposed to be due to TiO2 -binding catechol-like derivatives, which are then removed upon filtration.

18.
Chemphyschem ; 20(7): 972-983, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30784156

RESUMO

To investigate the role of the capping group in the solution and solid-state self-assembly of short peptide amphiphiles, dialanine and diphenylalanine have been linked via the N-terminus to a benzene (phenyl) and 3-naphthyl capping groups using three different methylene linkers; (CH2 )n , n=0-4 for the benezene and 0, 1 and 2 for the naphthalene capping group. Atomic force microscopy (AFM), oscillatory rheology, circular dichroism (CD), and IR analysis have been employed to understand the properties of these peptide-based hydrogels. Several X-ray structures of these short peptide gelators give useful conformational information regarding packing. A comparison of these solid state structures with their gel state properties yielded greater insights into the process of self-assembly in short peptide gelators, particularly in terms of the important role of C⋅⋅⋅H interactions appear to play in determining if a short aromatic peptide does form a gel or not.

19.
Bioconjug Chem ; 30(3): 503-514, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30742420

RESUMO

Multivalency plays a large role in many biological and synthetic systems. The past 20 years of research have seen an explosion in the study of multivalent drug delivery systems based on scaffolds such as dendrimers, polymers, and other nanoparticles. The results from these studies suggest that when it comes to the number of ligands, sometimes, to quote Shakespeare, "too much of a good thing" is an apt description. Recent theoretical studies on multivalency indicate that the field may have had a misplaced emphasis on maximizing binding strength where in fact it is the selectivity of multivalent drug delivery systems that is the key to success. This Topical Review will summarize these theoretical developments. We will then illustrate how these developments can be used to rationalize the immunoresponses and drug uptake mechanisms for multivalent systems and show the path forward toward the design of better multivalent drug delivery systems.


Assuntos
Dendrímeros/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Polímeros/química , Animais , Dendrímeros/metabolismo , Portadores de Fármacos/metabolismo , Humanos , Modelos Moleculares , Nanopartículas/metabolismo , Preparações Farmacêuticas/administração & dosagem , Farmacocinética , Polímeros/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo
20.
Inorg Chem ; 58(1): 495-505, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30561998

RESUMO

An in-depth study of the interaction of a trinuclear terbium(III)-dizinc(II) complex with an array of nucleotides differing in the type of nucleobase and number of phosphate groups, as well as cyclic versus acyclic variants, is presented. The study examined the nature of the interaction and the efficiency at which guanine was able to sensitize terbium(III) luminescence. Competitive binding and titration studies were performed to help establish the nature/mode of the interactions. These established that (1) interaction occurs by the coordination of phosphate groups to zinc(II) (in addition to uridine in the case of uridine monophosphate), (2) acyclic nucleotides bind more strongly than cyclic counterparts because of their higher negative charge, (3) guanine-containing nucleotides are able to sensitize terbium(III) luminescence with the efficiency of sensitization following the order guanosine monophosphate (GMP) > guanosine diphosphate > guanosine triphosphate because of the mode of binding, and (4) nucleoside monophosphates bind to a single zinc(II) ion, whereas di- and triphosphates appear to bind in a bridging mode between two host molecules. Furthermore, it has been shown that guanine is a sensitizer of terbium(III) luminescence. On the basis of the ability of GMP to effectively sensitize terbium(III)-based luminescence while cyclic GMP (cGMP) does not, the complex has been utilized to monitor the catalytic conversion of cGMP to GMP by a phosphodiesterase enzyme in real time using time-gated luminescence on a benchtop fluorimeter. The complex has the potential to find broad application in monitoring the activity of enzymes that process nucleotides (co)substrates, including high-throughput drug-screening programs.


Assuntos
Complexos de Coordenação/química , Guanosina Monofosfato/química , Diester Fosfórico Hidrolases/análise , Térbio/química , Zinco/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , GMP Cíclico/química , Ensaios Enzimáticos , Luz , Luminescência , Espectrofotometria , Água/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA