Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.887
Filtrar
1.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445521

RESUMO

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external stimuli such as temperature and pH as switches, these smart poly(aspartamide) derivatives can be used for convenient drug loading and controlled release. Here, we review the synthesis strategies for preparing these stimuli-responsive poly(aspartamide) derivatives and the latest developments in their applications as drug carriers.


Assuntos
Ácido Aspártico/análogos & derivados , Portadores de Fármacos/síntese química , Polímeros/síntese química , Ácido Aspártico/síntese química , Ácido Aspártico/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Polímeros/química , Temperatura
2.
Chem Pharm Bull (Tokyo) ; 69(8): 773-780, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334521

RESUMO

Multifunctional synthetic polymers can bind to target molecules and are therefore widely investigated in diagnostics, drug delivery carriers, and separation carriers. Because these polymers are synthesized from nonbiological components, purification processes (e.g., chromatography, dialysis, extraction, and centrifugation) must be conducted after the synthesis. Although several purification methods are used for polymer purification, few reports have revealed the influence of purification process on the functions of polymer. In this study, we demonstrated that the characteristics, function, and stability of synthetic polymer depend on the purification process. N-Isopropylacrylamide-based polymer nanoparticles (NPs) and melittin (i.e., honey bee venom) were used as a model of synthetic polymer and target toxic peptide, respectively. Synthesized NPs were purified by dialysis in methanol, acetone precipitation, or centrifugation. NPs purified by dialysis in ultrapure water were used as control NPs. Then, NP size, surface charge, toxin neutralization effect, and stability were determined. NP size did not considerably change by purification with centrifugation; however, it decreased by purification using dialysis in methanol and acetone precipitation compared with that of control NPs. The ζ-potential of NPs changed after each purification process compared with that of control NPs. The melittin neutralization efficiency of NPs depended on the purification process; i.e., it decreased by acetone precipitation and increased by dialysis in methanol and centrifugation compared with that of control NPs. Of note, the addition of methanol and acetone decreased NP stability. These studies implied the importance of considering the effect of the purification method on synthetic polymer function.


Assuntos
Nanopartículas/química , Polímeros/isolamento & purificação , Estrutura Molecular , Polímeros/síntese química , Polímeros/química
3.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443542

RESUMO

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. Broad-spectrum antimicrobial activity was observed, with reduction in both bacterial viability and overall biofilm mass. Further, PNPs displayed minimal fibroblast toxicity and high antimicrobial activity in an in vitro co-culture model comprising fibroblast cells and dual-species biofilms of Escherichia coli and Pseudomonas aeruginosa. This study highlights a potential clinical application of the presented polymeric platform.


Assuntos
Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Nanopartículas/química , Polímeros/farmacologia , Células 3T3 , Animais , Biomassa , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Polímeros/síntese química , Polímeros/química
4.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445293

RESUMO

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1ß, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.


Assuntos
Substitutos Ósseos/síntese química , Decanoatos/química , Durapatita/química , Glicerol/análogos & derivados , Polímeros/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Substitutos Ósseos/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Células Cultivadas , Feminino , Glicerol/química , Humanos , Invenções , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteogênese/efeitos dos fármacos , Polímeros/síntese química , Porosidade , Engenharia Tecidual/tendências
5.
Nat Commun ; 12(1): 4874, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385442

RESUMO

Biobased poly(γ-methyl-α-methylene-γ-butyrolactone) (PMMBL), an acrylic polymer bearing a cyclic lactone ring, has attracted increasing interest because it not only is biorenewable but also exhibits superior properties to petroleum-based linear analog poly(methyl methacrylate) (PMMA). However, such property enhancement has been limited to resistance to heat and solvent, and mechanically both types of polymers are equally brittle. Here we report the expeditious synthesis of well-defined PMMBL-based ABA tri-block copolymers (tri-BCPs)-enabled by dual-initiating and living frustrated Lewis pairs (FLPs)-which are thermoplastic elastomers showing much superior mechanical properties, especially at high working temperatures (80-130 °C), to those of PMMA-based tri-BCPs. The FLPs consist of a bulky organoaluminum Lewis acid and a series of newly designed bis(imino)phosphine superbases bridged by an alkyl linker, which promote living polymerization of MMBL. Uniquely, such bisphosphine superbases initiate the chain growth from both P-sites concurrently, enabling the accelerated synthesis of tri-BCPs in a one-pot, two-step procedure. The results from mechanistic studies, including the single crystal structure of the dually initiated active species, detailed polymerizations, and kinetic studies confirm the livingness of the polymerization and support the proposed polymerization mechanism featuring the dual initiation and subsequent chain growth from both P-sites of the superbase di-initiator.


Assuntos
4-Butirolactona/análogos & derivados , Elastômeros/química , Ácidos de Lewis/química , Fosfinas/química , Polímeros/química , 4-Butirolactona/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Cristalografia por Raios X , Elastômeros/síntese química , Cinética , Modelos Químicos , Estrutura Molecular , Polimerização , Polímeros/síntese química , Temperatura
6.
Int J Biol Macromol ; 182: 1953-1965, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062162

RESUMO

A durable and reversible acid-induced discoloration azobenzene UV-curable lignin-based waterborne polyurethane polymeric dye (EDA-ULPD) is prepared from lignin, azobenzene and pentaerythritol triacrylate(PETA) by chemical modification of waterborne polyurethane. Lignin and PETA are chemically bonded to the polyurethane chain to improve thermal stability, UV resistance and color fastness, while also endow the polymeric dye with UV curing performance, which is a green and environmentally friendly fixing way. The acid-induced discoloration property of EDA-ULPD with azobenzene chromophore side chain is comparable to those of 4-ethyl-4-2,2'-dihydroxy diethylamine azobenzene (EDA). As the pH value decreases from 7 to 1, the maximum absorption peak of EDA-ULPD from 420 nm to 530 nm, and the color change from yellow to pink due to the transformation of EDA molecular structure from diazo to hydrazone. Interestingly, when EDA-ULPD is fixed to the fabric in the way of UV curing, its printed fabric exhibits the performance of high concentration acid-induced discoloration (1 mol·L-1 HCl) due to the cross-linked structure formed by EDA-ULPD. The acid-induced discoloration property of EDA-ULPD printed fabrics also presents outstanding repetitious stability. The stimulus response printed fabric with reversible high concentration acid discoloration possesses a broad application prospect in smart textiles.


Assuntos
Ácidos/química , Compostos Azo/química , Corantes/química , Lignina/química , Polímeros/química , Poliuretanos/química , Raios Ultravioleta , Água/química , Compostos Azo/síntese química , Varredura Diferencial de Calorimetria , Cor , Corantes/síntese química , Reagentes para Ligações Cruzadas/química , Peso Molecular , Polímeros/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Infravermelho , Temperatura
8.
AAPS PharmSciTech ; 22(5): 169, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34080086

RESUMO

Lutein has been used as a dietary supplement for the treatment of eye diseases, especially age-related macular degeneration. For oral formulations, we investigated lutein stability in artificial set-ups mimicking different physiological conditions and found that lutein was degraded over time under acidic conditions. To enhance the stability of lutein upon oral intake, we developed enteric-coated lutein solid dispersions (SD) by applying a polymer, hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF), through a solvent-controlled precipitation method. The SD were characterized in crystallinity, morphology, and drug entrapment. In the dissolution profile of lutein SD, a F80 formulation showed resistance toward the acidic environment under simulated gastric conditions while exhibiting a bursting drug release under simulated intestinal conditions. Our results highlight the potential use of HPMCAS-LF as an effective matrix to enhance lutein bioavailability during oral delivery and to provide novel insights into the eye-care supplement industry, with direct benefits for the health of patients.


Assuntos
Luteína/síntese química , Luteína/farmacocinética , Metilcelulose/análogos & derivados , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Metilcelulose/síntese química , Metilcelulose/farmacocinética , Polímeros/síntese química , Polímeros/farmacocinética , Solubilidade , Solventes , Difração de Raios X/métodos
9.
AAPS PharmSciTech ; 22(5): 181, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129154

RESUMO

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (ß-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-ßCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-ßCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.


Assuntos
Acrilamidas/síntese química , Aciclovir/síntese química , Alcanossulfonatos/síntese química , Derivados da Hipromelose/síntese química , Polimerização , beta-Ciclodextrinas/síntese química , Acrilamidas/administração & dosagem , Aciclovir/administração & dosagem , Administração Oral , Alcanossulfonatos/administração & dosagem , Animais , Antivirais/administração & dosagem , Antivirais/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Derivados da Hipromelose/administração & dosagem , Masculino , Tamanho da Partícula , Polímeros/administração & dosagem , Polímeros/síntese química , Coelhos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos , beta-Ciclodextrinas/administração & dosagem
10.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069278

RESUMO

Clinical outcomes of conventional drug combinations are not ideal due to high toxicity to healthy tissues. Cisplatin (CDDP) is the standard component for many cancer treatments, yet its principal dose-limiting side effect is nephrotoxicity. Thus, CDDP is commonly used in combination with other drugs, such as the autophagy inhibitor chloroquine (CQ), to enhance tumor cell killing efficacy and prevent the development of chemoresistance. In addition, nanocarrier-based drug delivery systems can overcome chemotherapy limitations, decreasing side effects and increasing tumor accumulation. The aim of this study was to evaluate the toxicity of CQ and CDDP against tumor and non-tumor cells when used in a combined treatment. For this purpose, two types of micelles based on Pluronic® F127 hybrid dendritic-linear-dendritic block copolymers (HDLDBCs) modified with polyester or poly(esteramide) dendrons derived from 2,2'-bis(hydroxymethyl)propionic acid (HDLDBC-bMPA) or 2,2'-bis(glycyloxymethyl)propionic acid (HDLDBC-bGMPA) were explored as delivery nanocarriers. Our results indicated that the combined treatment with HDLDBC-bMPA(CQ) or HDLDBC-bGMPA(CQ) and CDDP increased cytotoxicity in tumor cells compared to the single treatment with CDDP. Encapsulations demonstrated less short-term cytotoxicity individually or when used in combination compared to the free drugs. However, and more importantly, a low degree of cytotoxicity against non-tumor cells was maintained, even when drugs were given simultaneously.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Micelas , Polímeros/química , Células A549 , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cloroquina/administração & dosagem , Cloroquina/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Células HeLa , Humanos , Poloxâmero/química , Polímeros/síntese química
11.
Molecules ; 26(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067052

RESUMO

Trends in the dynamically developing application of biocatalysis for the synthesis and modification of polymers over the past 5 years are considered, with an emphasis on the production of biodegradable, biocompatible and functional polymeric materials oriented to medical applications. The possibilities of using enzymes not only as catalysts for polymerization but also for the preparation of monomers for polymerization or oligomers for block copolymerization are considered. Special attention is paid to the prospects and existing limitations of biocatalytic production of new synthetic biopolymers based on natural compounds and monomers from biomass, which can lead to a huge variety of functional biomaterials. The existing experience and perspectives for the integration of bio- and chemocatalysis in this area are discussed.


Assuntos
Biocatálise , Polímeros/síntese química , Enzimas/metabolismo , Polimerização , Polímeros/química , Engenharia de Proteínas , Publicações
12.
Chem Commun (Camb) ; 57(46): 5646-5649, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33977983

RESUMO

A covalent organic framework (COF)-engineered polydopamine core-shell nanoplatform (PDA@COF) was developed. The ultrasmall pores and abundant functional sites of the COF endowed the nanoplatform with enhanced drug loading capacity and diminished drug leakage effect. Multimodal imaging-guided photothermal chemo-synergistic tumor-targeted therapy was realized after rational functionalization. This work offers new insights for developing COF-based multifunctional theranostic systems.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Indóis/química , Nanopartículas/química , Terapia Fototérmica , Polímeros/química , Animais , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Lasers , Camundongos , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Imagem Óptica , Tamanho da Partícula , Polímeros/síntese química , Propriedades de Superfície
13.
Chem Commun (Camb) ; 57(50): 6153-6156, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34042925

RESUMO

We report here the first example of the direct synthesis of polyureas from the dehydrogenative coupling of diamines and methanol using a ruthenium pincer catalyst. The present methodology replaces the use of toxic diisocyanates, conventionally used for the production of polyureas, with methanol, which is renewable, less toxic, and cheaper, making the overall process safer and more sustainable. Further advantages of the current method have been demonstrated by the synthesis of a renewable, a chiral, and the first 13C-labelled polyurea.


Assuntos
Diaminas/química , Metanol/química , Polímeros/síntese química , Catálise , Hidrogenação , Estrutura Molecular , Polímeros/química , Rutênio
14.
AAPS PharmSciTech ; 22(4): 149, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961149

RESUMO

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.


Assuntos
Compostos de Alumínio/síntese química , Cápsulas/síntese química , Encapsulamento de Células/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Doença de Parkinson , Compostos de Sódio/síntese química , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/metabolismo , Animais , Encéfalo/metabolismo , Cápsulas/administração & dosagem , Cápsulas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dopamina/metabolismo , Camundongos , Células PC12 , Doença de Parkinson/metabolismo , Doença de Parkinson/terapia , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/metabolismo , Estudos Prospectivos , Células RAW 264.7 , Ratos , Compostos de Sódio/administração & dosagem , Compostos de Sódio/metabolismo , Resultado do Tratamento
15.
AAPS PharmSciTech ; 22(4): 154, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33983536

RESUMO

In twin screw melt granulation, granules are produced by passing mixtures of drug substances and polymeric binders through twin screw extruder such that temperatures are maintained below melting point of drugs but above glass transition of polymers used, whereby the polymers coat surfaces of drug particles and cause their agglomeration into granules. Since various formulation factors, such as binder type and concentration, and processing variables like extrusion temperature, screw configuration, and screw speed, can influence the granulation process, the present investigation was undertaken to study their effects on tabletability of granules produced. Three different types of polymeric binders, Klucel® EXF (hydroxypropyl cellulose), Eudragit® EPO (polyacrylate binder), and Soluplus® (polyvinyl caprolactam-co-vinyl acetate-ethylene glycol graft polymer), were used at 2, 5, and 10% concentrations. Metformin hydrochloride (HCl) (mp: 222°C) and acetaminophen (mp: 169°C) were used as model drugs, and drug-polymer mixtures with metformin HCl were extruded at 180, 160, and 130°C, while those with acetaminophen were extruded at 130 and 110°C. Other process variables included screw configurations: low, medium, and high shear for metformin HCl, and low and medium shear for acetaminophen; feed rates: 20 and 60 g/min; and screw speed of 100 and 300 RPM. Formulation and process variables had significant impact on tabletability. The target tensile strength of ≥2 MPa could be obtained with all polymers and at all processing temperatures when metformin HCl was granulated at 180°C and acetaminophen at 130°C. At other temperatures, the target tensile strength could be achieved at certain specific sets of processing conditions.


Assuntos
Acetaminofen/síntese química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Metformina/síntese química , Polímeros/síntese química , Analgésicos não Narcóticos/síntese química , Congelamento , Hipoglicemiantes/síntese química , Tamanho da Partícula , Comprimidos , Resistência à Tração
16.
Mar Drugs ; 19(5)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947080

RESUMO

Marine polycyclic ether natural products have gained significant interest from the chemical community due to their impressively huge molecular architecture and diverse biological functions. The structure assignment of this class of extraordinarily complex natural products has mainly relied on NMR spectroscopic analysis. However, NMR spectroscopic analysis has its own limitations, including configurational assignment of stereogenic centers within conformationally flexible systems. Chemical shift deviation analysis of synthetic model compounds is a reliable means to assign the relative configuration of "difficult" stereogenic centers. The complete configurational assignment must be ultimately established through total synthesis. The aim of this review is to summarize the indispensable role of organic synthesis in stereochemical assignment of marine polycyclic ethers.


Assuntos
Organismos Aquáticos/metabolismo , Éteres Cíclicos/síntese química , Técnicas de Química Sintética , Ciguatoxinas/síntese química , Ciguatoxinas/isolamento & purificação , Éteres/síntese química , Éteres/isolamento & purificação , Éteres Cíclicos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Toxinas Marinhas/síntese química , Toxinas Marinhas/isolamento & purificação , Estrutura Molecular , Oxocinas/síntese química , Oxocinas/isolamento & purificação , Polímeros/síntese química , Polímeros/isolamento & purificação , Metabolismo Secundário , Estereoisomerismo , Relação Estrutura-Atividade
17.
Chemphyschem ; 22(12): 1208-1218, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33851772

RESUMO

The cobalt substituted polyoxotungstate [Co6 (H2 O)2 (α-B-PW9 O34 )2 (PW6 O26 )]17- (Co6) displays fast electron transfer (ET) kinetics to photogenerated RuIII (bpy)3 3+ , 4 to 5 orders of magnitude faster than the corresponding ET observed for cobalt oxide nanoparticles. Mechanistic evidence has been acquired indicating that: (i) the one-electron oxidation of Co6 involves Co(II) aquo or Co(II) hydroxo groups (abbreviated as Co6(II)-OH2 and Co6(II)-OH, respectively, whose speciation in aqueous solution is associated to a pKa of 7.6), and generates a Co(III)-OH moiety (Co6(III)-OH), as proven by transient absorption spectroscopy; (ii) at pH>pKa , the Co6(II)-OH→RuIII (bpy)3 3+ ET occurs via bimolecular kinetics, with a rate constant k close to the diffusion limit and dependent on the ionic strength of the medium, consistent with reaction between charged species; (iii) at pH

Assuntos
Complexos de Coordenação/química , Elétrons , Compostos Organometálicos/química , Polímeros/química , Prótons , Compostos de Tungstênio/química , Cobalto/química , Complexos de Coordenação/síntese química , Cinética , Luz , Compostos Organometálicos/efeitos da radiação , Oxidantes/química , Oxidantes/efeitos da radiação , Oxirredução , Polímeros/síntese química , Rutênio/química , Rutênio/efeitos da radiação , Compostos de Tungstênio/síntese química , Água/química
18.
Acc Chem Res ; 54(10): 2397-2408, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33914498

RESUMO

Proteins contain a level of complexity-secondary and tertiary structures-that polymer chemists aim to imitate. The bottom-up synthesis of protein-mimicking polymers mastering sequence variability and dispersity remains challenging. Incorporating polymers with predefined secondary structures, such as helices and π-π stacking sheets, into block copolymers circumvents the issue of designing and predicting one facet of their 3D architecture. Block copolymers with well-defined secondary-structure elements formed by covalent chain extension or supramolecular self-assembly may be considered for localized tertiary structures.In this Account, we describe a strategy toward block copolymers composed of units bearing well-defined secondary structures mixed in a "plug-and-play" manner that approaches a modicum of the versatility seen in nature. Our early efforts focused on the concept of single-chain collapse to achieve folded secondary structures through either hydrogen bonding or quadrupole attractive forces. These cases, however, required high dilution. Therefore, we turned to the ring-opening metathesis polymerization (ROMP) of [2.2]paracyclophane-1,9-dienes (pCpd), which forms conjugated, fluorescent poly(p-phenylenevinylene)s (PPVs) evocative of ß-sheets. Helical building blocks arise from polymers such as poly(isocyanide)s (PICs) or poly(methacrylamide)s (PMAcs) containing bulky, chiral side groups while the coil motif can be represented by any flexible chain; we frequently chose poly(styrene) (PS) or poly(norbornene) (PNB). We installed moieties for supramolecular assembly at the chain ends of our "sheets" to combine them with complementary helical or coil-shaped polymeric building blocks.Assembling hierarchical materials tantamount to the complexity of proteins requires directional interactions with high specificity, covalent chain extension, or a combination of both chemistries. Our design is based on functionalized reversible addition-fragmentation chain-transfer (RAFT) agents that allowed for the introduction of recognition motifs at the terminus of building blocks and chain-terminating agents (CTAs) that enabled the macroinitiation of helical polymers from the chain end of ROMP-generated sheets and/or coils. To achieve triblock copolymers with a heterotelechelic helix, we relied on supramolecular assembly with helix and coil-shaped building blocks. Our most diverse structures to date comprised a middle block of PPV sheets, parallel or antiparallel, and supramolecularly or covalently linked, respectively, end-functionalized with molecular recognition units (MRUs) for orthogonal supramolecular assembly. We explored PPV sheets with multiple folds achieved by chain extension using alternating pCpd and phenyl-pentafluorophenyl ß-hairpin turns. Using single-molecule polarization spectroscopy, we showed that folding occurs preferentially in multistranded over double-stranded PPV sheets. Our strategy toward protein-mimicking and foldable polymers demonstrates an efficient route toward higher ordered, well-characterized materials by taking advantage of polymers that naturally manifest secondary structures. Our studies demonstrate the retention of distinct architectures after complex assembly, a paradigm that we believe may extend to other polymeric folding systems.


Assuntos
Polímeros/química , Substâncias Macromoleculares/química , Modelos Moleculares , Estrutura Molecular , Polimerização , Polímeros/síntese química
19.
J Mater Chem B ; 9(13): 2979-2992, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885662

RESUMO

Hydrogels are cross-linked hydrophilic macromolecules that contain a certain amount of water. Due to their biocompatible, highly tunable and hydrophilic nature, hydrogels have attracted much attention in the applications of chemical, biomedical and pharmaceutical fields over the past twenty years. In particular, thermo-sensitive hydrogels, which can undergo phase transition or swell/deswell as ambient temperature changes, endow the drug delivery system with enhanced local drug penetration, desirable spatial and temporal control, and improved drug bioavailability. These merits facilitate their extensive applications in drug delivery. In this review, we focus on advances in the development of different thermo-sensitive polymers as a scaffold for drug delivery, including poly(N-isopropylacrylamide) (pNIPAAM), poloxamer, polyethylene glycol/poly(lactic acid)co-(glycolic acid) (PEG/PLGA), and chitosan. The state-of-the-art thermo-sensitive hydrogels for various pharmaceutical applications, such as anti-tumor drug delivery, transdermal drug delivery, ocular drug delivery, nasal drug delivery, and buccal drug delivery, are elaborated. Finally, the future research perspectives and challenges are also discussed, which could facilitate the translation of thermo-sensitive hydrogels for drug delivery from bench to bedside.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis/química , Polímeros/química , Temperatura , Animais , Humanos , Hidrogéis/síntese química , Interações Hidrofóbicas e Hidrofílicas , Polímeros/síntese química
20.
J Mater Chem B ; 9(13): 3055-3067, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885667

RESUMO

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against different cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing cisplatin-resistant human lung cancer cells (A549R) under amplified oxidative stress using a vesicular nanoreactor for simultaneous cisplatin delivery and H2O2 generation. We engineer the nanoreactor by the self-assembly of the amphiphilic diblock copolymers to co-deliver glucose oxidase (GOD) and cisplatin (Cis) (Cis/GOD@Bz-V). Cis/GOD@Bz-V was rationally designed to stay impermeable during blood circulation while mild acidity (pH 6.5-6.8) can activate its molecular-weight selective membrane permeability and release cisplatin locally. Diffusion of small molecules such as oxygen and glucose across the membranes can induce the in situ generation of superfluous H2O2 to promote cellular oxidative stress and sensitize A549R cells via activation of pro-apoptotic pathways. Cis/GOD@Bz-V nanoreactors could effectively kill A549R at pH 6.8 in the presence of glucose by the combination of H2O2 generation and cisplatin release. Growth of A549R xenograft tumors can be inhibited efficiently without the obvious toxic side effects via the systemic administration of Cis/GOD@Bz-V. Accordingly, the tumor acidity-activable cisplatin-loaded nanoreactors show great potential to enhance the therapeutic efficacy against cisplatin-resistant cancers.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Nanotecnologia , Polímeros/farmacologia , Células A549 , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Nanotecnologia/instrumentação , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Polímeros/síntese química , Polímeros/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...