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1.
Int J Biol Macromol ; 234: 123715, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36801278

RESUMO

Plastics play an essential role in food packaging; their primary function is to preserve the nature of the food, ensure adequate shelf life and ensure food safety. Plastics are being produced on a global scale in excess of 320 million tonnes annually, with demand rising to reflect the material in wide range of applications. Nowadays, the packaging industry is a significant consumer of synthetic plastic made from fossil fuels. Petrochemical-based plastics are regarded as the preferred material for packaging. Nonetheless, using these plastics in large quantities results in a long-standing environment. Environmental pollution and the depletion of fossil fuels have prompted researchers and manufacturers to develop eco-friendly biodegradable polymers to replace petrochemical-based polymers. As a result, the production of eco-friendly food packaging material has sparked increased interest as a viable alternative to petrochemical-based polymers. Polylactic acid (PLA) is one of the compostable thermoplastic biopolymers that is biodegradable and renewable in nature. High-molecular-weight PLA can be used to produce fibres, flexible, non-wovens, hard and durable materials (100,000 Da or even higher).The chapter focuses on food packaging techniques, food industry waste, biopolymers, their classification, PLA synthesis, the importance of PLA properties for food packaging, and technologies used to process PLA in food packaging.


Assuntos
Plásticos Biodegradáveis , Embalagem de Alimentos , Química Verde , Poliésteres , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Biopolímeros/química , Fermentação , Embalagem de Alimentos/métodos , Química Verde/métodos , Poliésteres/síntese química , Poliésteres/química , Polimerização , Humanos , Animais
2.
Int J Mol Sci ; 23(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35163372

RESUMO

Sucrose-1,6-hexamethylene diisocyanate (HDI) cooligomers were synthesized and used as new polyols for poly(ε-caprolactone) (PCL)-based polyurethanes. The polyaddition reaction of sucrose and HDI was monitored by MALDI-TOF MS. It was found that by selecting appropriate reaction conditions, mostly linear oligomer chains containing 16 sucrose units could be obtained. For the synthesis of polyurethane networks, prepolymers were prepared by the reaction of poly(ε-caprolactone) (PCL, 10 kg/mol) with HDI or 4,4'-methylene diphenyl diisocyanate (MDI) and were reacted with sucrose-HDI cooligomers. The so-obtained sucrose-containing polyurethanes were characterized by means of attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FT IR), swelling, mechanical (uniaxial tensile tests) and differential scanning calorimetry (DSC).


Assuntos
Isocianatos/química , Poliuretanos/síntese química , Sacarose/química , Varredura Diferencial de Calorimetria , Teste de Materiais , Poliésteres/síntese química , Poliésteres/química , Poliuretanos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
3.
Molecules ; 27(4)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35209201

RESUMO

The need for biodegradable and biocompatible polymers is growing quickly, particularly in the biomedical and environmental industries. Cellulose acetate, a natural polysaccharide, can be taken from plants and modified with polycaprolactone to improve its characteristics for a number of uses, including biomedical applications and food packaging. Cellulose acetate-g-polycaprolactone was prepared by a three-step reaction: First, polymerization of ε-caprolactone via ring-opening polymerization (ROP) reaction using 2-hydroxyethyl methacrylate (HEMA) and functionalization of polycaprolactone(PCL) by introducing NCO on the hydroxyl end of the HEMA-PCL using hexamethyl lenediisocyanate(HDI) were carried out. Then, the NCO-HEMA-PCL was grafted onto cellulose acetate (using the "grafting to" method). The polycaprolactone grafted cellulose acetate was confirmed by FTIR, the thermal characteristics of the copolymers were investigated by DSC and TGA, and the hydrophobicity was analyzed via water CA measurement. Introducing NCO-PCL to cellulose acetate increased the thermal stability. The contact angle of the unreacted PCL was higher than that of cellulose acetate-g-PCL, and it increased when the chain length increased. The CA-g-PCL50, CA-g-PCL100, and CA-g-PCL200 showed very high inhibition zones for all three bacteria tested (E. coli, S. aureus, and P. aeruginosa).


Assuntos
Antibacterianos , Bactérias/crescimento & desenvolvimento , Celulose/análogos & derivados , Embalagem de Alimentos , Poliésteres , Polimerização , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Celulose/síntese química , Celulose/química , Celulose/farmacologia , Poliésteres/síntese química , Poliésteres/química , Poliésteres/farmacologia
4.
Molecules ; 27(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35164403

RESUMO

Aliphatic polyesters are the most common type of biodegradable synthetic polymer used in many pharmaceutical applications nowadays. This report describes the ring-opening polymerization (ROP) of l-lactide (L-LA), ε-caprolactone (CL) and glycolide (Gly) in the presence of a simple, inexpensive and convenient PEG200-BiOct3 catalytic system. The chemical structures of the obtained copolymers were characterized by 1H- or 13C-NMR. GPC was used to estimate the average molecular weight of the resulting polyesters, whereas TGA and DSC were employed to determine the thermal properties of polymeric products. The effects of temperature, reaction time, and catalyst content on the polymerization process were investigated. Importantly, the obtained polyesters were not cyto- or genotoxic, which is significant in terms of the potential for medical applications (e.g., for drug delivery systems). As a result of transesterification, the copolymers obtained had a random distribution of comonomer units along the polymer chain. The thermal analysis indicated an amorphous nature of poly(l-lactide-co-ε-caprolactone) (PLACL) and a low degree of crystallinity of poly(ε-caprolactone-co-glycolide) (PCLGA, Xc = 15.1%), in accordance with the microstructures with random distributions and short sequences of comonomer units (l = 1.02-2.82). Significant differences in reactivity were observed among comonomers, confirming preferential ring opening of L-LA during the copolymerization process.


Assuntos
Bismuto/química , Caproatos/química , Dioxanos/química , Lactonas/química , Ácido Poliglicólico/química , Polimerização , Caproatos/síntese química , Catálise , Dioxanos/síntese química , Lactonas/síntese química , Poliésteres/síntese química , Poliésteres/química , Ácido Poliglicólico/síntese química , Temperatura
5.
Molecules ; 27(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35011561

RESUMO

In this work, the feasibility of replacing petroleum-based poly(ethylene terephthalate) (PET) with fully bio-based copolyesters derived from dimethyl 2,5-thiophenedicarboxylate (DMTD), dimethyl 2,5-dimethoxyterephthalate (DMDMT), and polysaccharide-derived 1,6-hexanediol (HDO) was investigated. A systematic study of structure-property relationship revealed that the properties of these poly(thiophene-aromatic) copolyesters (PHS(20-90)) can be tailored by varying the ratio of diester monomers in the reaction, whereby an increase in DMTD content noticeably shortened the reaction time in the transesterification step due to its higher reactivity as compared with DMDMT. The copolyesters had weight-average molar masses (Mw) between 27,500 and 38,800 g/mol, and dispersity D of 2.0-2.5. The different polarity and stability of heterocyclic DMTD provided an efficient mean to tailor the crystallization ability of the copolyesters, which in turn affected the thermal and mechanical performance. The glass transition temperature (Tg) could be tuned from 70-100 °C, while the tensile strength was in a range of 23-80 MPa. The obtained results confirmed that the co-monomers were successfully inserted into the copolyester chains. As compared with commercial poly(ethylene terephthalate), the copolyesters displayed not only enhanced susceptibility to hydrolysis, but also appreciable biodegradability by lipases, with weight losses of up to 16% by weight after 28 weeks of incubation.


Assuntos
Ácidos/química , Poliésteres/síntese química , Polissacarídeos/química , Tiofenos/síntese química , Técnicas de Química Sintética , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Poliésteres/química , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração , Termogravimetria , Tiofenos/química
6.
Eur J Pharm Biopharm ; 170: 170-178, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34963657

RESUMO

Ulcerative colitis (UC) is a refractory inflammatory bowel disease that causes inflammation and ulcers in the digestive tract, and significantly reduces the patient's quality of life. While existing UC treatments have many challenges, nanotechnology, and small interfering RNA (siRNA) based formulations are novel and promising for UC treatment. We previously reported that intravenous administration of MPEG-PCL-CH2R4H2C nanomicelles had high inflammatory site accumulation and remarkable therapeutic effects on rheumatoid arthritis by a phenomenon similar to enhanced permeability and retention effect. In this study, we investigated the effects of siRNA delivered using MPEG-PCL-CH2R4H2C nanomicelles through intravenous administration to the inflammation site of dextran sulfate sodium-induced colitis mice. The MPEG-PCL-CH2R4H2C micelles had optimum physical properties and high siRNA compaction ability. Moreover, model-siRNA delivered through MPEG-PCL-CH2R4H2C showed higher accumulation in the inflammatory site than that of the naked siRNA. Furthermore, intravenous administration of MPEG-PCL-CH2R4H2C/siRelA micelles, targeting siRelA, a subunit of NF-κB, significantly decreased the shortening of large intestine, clinical score, and production of inflammatory cytokines compared the 5-ASA and naked siRelA. These results suggest that MPEG-PCL-CH2R4H2C is a useful carrier for the systemic delivery and accumulation of siRNA, thus improving its therapeutic effect.


Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Poliésteres/administração & dosagem , Polietilenoglicóis/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Administração Intravenosa , Animais , Peptídeos Penetradores de Células/síntese química , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Micelas , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Polímeros/síntese química
7.
Molecules ; 26(24)2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34946753

RESUMO

Levoglucosenone (LGO) is a cellulose-derived molecule that is present commercially on a multi-ton/year scale. Taking advantage of the α,ß-conjugated ketone of LGO, a new citronellol-containing 5-membered lactone (HBO-citro) was synthesized through a one-pot two-step pathway involving oxa-Michael addition and Baeyer-Villiger oxidation. The solvent-free treatment of HBO-citro with NaBH4 at room temperature led to the full reduction of the lactone moiety which gave a novel fully renewable triol monomer having a citronellol side chain (Triol-citro). Noticeably, by simply changing the reducing agent, temperature and reaction duration, the partial reduction of HBO-citro can be achieved to yield a mixture of 5- and 6-membered Lactol-citro molecules. Triol-citro was chosen to prepare functional renewable polyesters having citronellol pendant chains via polycondensation reactions with diacyl chlorides having different chain lengths. Good thermal stability (Td5% up to 170 °C) and low glass transition temperatures (as low as -42 °C) were registered for the polyesters obtained. The polymers were then hydrolyzed using a commercial lipase from Thermomyces lanuginosus (Lipopan® 50 BG) to assess their biodegradability. A higher degradation profile was found for the polyesters prepared using co-monomers (acyl chlorides) having longer chain lengths. This is likely due to the decreased steric hindrance around the ester bonds which allowed enhanced accessibility of the enzyme.


Assuntos
Monoterpenos Acíclicos/metabolismo , Celulose/metabolismo , Lipase/metabolismo , Poliésteres/metabolismo , Monoterpenos Acíclicos/química , Biodegradação Ambiental , Celulose/química , Eurotiales/enzimologia , Lipase/química , Estrutura Molecular , Poliésteres/síntese química , Poliésteres/química , Temperatura
8.
Int J Mol Sci ; 22(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34830089

RESUMO

This study concerns bio-based urethane prepolymers. The relationship between the chemical structure and the thermal and processing parameters of bio-based isocyanate-terminated ether and ester-urethane prepolymers was investigated. Bio-based prepolymers were obtained with the use of bio-monomers such as bio-based diisocyanate, bio-based polyether polyol or polyester polyols. In addition to their composition, the bio-based prepolymers were different in the content of iso-cyanate groups content (ca. 6 and 8%). The process of pre-polymerization and the obtained bio-based prepolymers were analyzed by determining the content of unreacted NCO groups, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, thermogravimetry, and rheological measurements. The research conducted facilitated the evaluation of the properties and processability of urethane prepolymers based on natural components. The results indicate that a significant impact on the processability has the origin the polyol ingredient as well as the NCO content. The thermal stability of all of the prepolymers is similar. A prepolymer based on a poly-ether polyol is characterized by a lower viscosity at a lower temperature than the prepolymer based on a polyester polyol. The viscosity value depends on the NCO content.


Assuntos
Poliésteres , Polímeros , Poliuretanos , Ésteres/química , Éter/química , Peso Molecular , Poliésteres/síntese química , Poliésteres/química , Polimerização , Polímeros/síntese química , Polímeros/química , Poliuretanos/síntese química , Poliuretanos/química , Propriedades de Superfície
9.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638747

RESUMO

Amphiphilic copolymers with pendant functional groups in polyester segments are widely used in nanomedicine. These enriched functionalities are designed to form covalent conjugates with payloads or provide additional stabilization effects for encapsulated drugs. A general method is successfully developed for the efficient preparation of functional biodegradable PEG-polyester copolymers via click chemistry. Firstly, in the presence of mPEG as initiator, Sn(Oct)2-catalyzed ring-opening polymerization of the α-alkynyl functionalized lactone with D,L-lactide or ε-caprolactone afforded linear mPEG-polyesters bearing multiple pendant alkynyl groups. Kinetic studies indicated the formation of random copolymers. Through copper-catalyzed azide-alkyne cycloaddition reaction, various small azido molecules with different functionalities to polyester segments are efficiently grafted. The molecular weights, polydispersities and grafting efficiencies of azido molecules of these copolymers were investigated by NMR and GPC. Secondly, it is demonstrated that the resulting amphiphilic functional copolymers with low CMC values could self-assemble to form nanoparticles in aqueous media. In addition, the in vitro degradation study and cytotoxicity assays indicated the excellent biodegradability and low cytotoxicity of these copolymers. This work provides a general approach toward the preparation of functional PEG-polyester copolymers in a quite efficient way, which may further facilitate the application of functional PEG-polyesters as drug delivery materials.


Assuntos
Plásticos Biodegradáveis , Química Click , Sistemas de Liberação de Medicamentos , Poliésteres , Polietilenoglicóis/química , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacocinética , Plásticos Biodegradáveis/farmacologia , Catálise , Células HeLa , Humanos , Poliésteres/síntese química , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Compostos de Estanho/química
10.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445200

RESUMO

In the present work, different hydrolases were adsorbed onto polypropylene beads to investigate their activity both in short-esters and polyesters synthesis. The software MODDE® Pro 13 (Sartorius) was used to develop a full-factorial design of experiments (DoE) to analyse the thermostability and selectivity of the immobilized enzyme towards alcohols and acids with different chain lengths in short-esters synthesis reactions. The temperature optima of Candida antarctica lipase B (CaLB), Humicola insolens cutinase (HiC), and Thermobifida cellulosilytica cutinase 1 (Thc_Cut1) were 85 °C, 70 °C, and 50 °C. CaLB and HiC preferred long-chain alcohols and acids as substrate in contrast to Thc_Cut1, which was more active on short-chain monomers. Polymerization of different esters as building blocks was carried out to confirm the applicability of the obtained model on larger macromolecules. The selectivity of both CaLB and HiC was investigated and best results were obtained for dimethyl sebacate (DMSe), leading to polyesters with a Mw of 18 kDa and 6 kDa. For the polymerization of dimethyl adipate (DMA) with BDO and ODO, higher molecular masses were obtained when using CaLB onto polypropylene beads (CaLB_PP) as compared with CaLB immobilized on macroporous acrylic resin beads (i.e., Novozym 435). Namely, for BDO the Mn were 7500 and 4300 Da and for ODO 8100 and 5000 Da for CaLB_PP and for the commercial enzymes, respectively. Thc_Cut1 led to polymers with lower molecular masses, with Mn < 1 kDa. This enzyme showed a temperature optimum of 50 °C with 63% of DMA and BDO when compared to 54% and 27%, at 70 °C and at 85 °C, respectively.


Assuntos
Ésteres/síntese química , Aromatizantes/síntese química , Poliésteres/síntese química , Biocatálise , Candida/enzimologia , Hidrolases de Éster Carboxílico/química , Enzimas Imobilizadas/química , Gênero de Fungos Humicola/enzimologia , Proteínas Fúngicas/química , Lipase/química , Polimerização , Thermobifida/enzimologia
11.
AAPS PharmSciTech ; 22(6): 205, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34286391

RESUMO

Drug-loaded electrospun fibers have attracted increasing attention as a promising wound dressing material due to their capability of preventing from infections and inflammation and maintaining an appropriate environment for wound healing. In this study, polylactic acid (PLA), which is widely used in wound management, was chosen as electrospinnable polymer. A triterpene extract (TE) from the outer bark of birch known for its anti-inflammatory, antiviral, antibacterial, and wound healing effects was chosen to produce TE-loaded PLA electrospun fibers for wound dressing. A binary solvent system of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) was employed, and the ratio of the solvents was optimized for preparing smooth and uniform fibers. The morphology of TE-loaded PLA electrospun fibers was investigated by scanning electron microscopy (SEM). The entrapment of TE in PLA fibers was confirmed by confocal laser scanning microscopy (CLSM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze the solid state of TE in PLA fibers. The release behavior of TE was assayed by a shaking flask method for a period of 96 h. The results revealed that TE-loaded electrospun PLA microfibers could be reliably prepared and are promising future candidates in wound therapy.


Assuntos
Bandagens , Betula/química , Nanofibras/química , Casca de Planta/química , Poliésteres/síntese química , Triterpenos/síntese química , Antibacterianos/análise , Antibacterianos/síntese química , Química Farmacêutica/métodos , Nanofibras/análise , Extratos Vegetais/análise , Extratos Vegetais/síntese química , Poliésteres/análise , Triterpenos/análise
12.
ACS Appl Mater Interfaces ; 13(29): 33905-33914, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34278780

RESUMO

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Acrilatos/síntese química , Acrilatos/química , Animais , Antineoplásicos/química , Compostos de Boro/química , Compostos de Boro/uso terapêutico , Linhagem Celular Tumoral , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos , Paclitaxel/química , Paclitaxel/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Pirróis/química , Pirróis/uso terapêutico , Oxigênio Singlete/metabolismo
13.
Chem Rec ; 21(8): 1898-1911, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34197009

RESUMO

Biodegradable polyesters such as poly(ϵ-caprolactone) (PCL) and poly(lactic acid) (PLA) have been considered for use in several areas, such as drug delivery devices, sutures, tissue engineering, and GBR membranes, due to its bio-renewability, biodegradability, and biocompatibility. Several synthetic techniques for the preparation of polyesters have been reported in the literature, amongst which the ring-opening polymerization (ROP) of cyclic esters is the most efficient. A convenient approach to access iso-selective PLAs is polymerization of racemic lactide (rac-LA), which shows excellent stereoregularity without the need for costly chiral auxiliaries or ligands. In this personal account, we review a series of methods that have been practiced to the synthesis of biodegradable polyesters from various cyclic monomers using alkali and alkaline earth metal complexes as efficient catalysts.


Assuntos
Complexos de Coordenação/química , Metais Alcalinos/química , Metais Alcalinoterrosos/química , Poliésteres/química , Boranos/química , Catálise , Calcogênios/química , Ciclização , Ésteres/química , Poliésteres/síntese química
14.
AAPS PharmSciTech ; 22(5): 191, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34169366

RESUMO

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has demonstrated notable clinical activity in cancer immunotherapy, but it is limited by systemic toxicities, poor bioavailability, rapid clearance, and instability in vivo. Nanoparticles (NPs) may overcome these limitations and provide a mechanism for passive targeting of tumors. This study aimed to develop GM-CSF-loaded PLGA/PLGA-PEG NPs and evaluate them in vitro as a potential candidate for in vivo administration. NPs were created by a phase-separation technique that did not require toxic/protein-denaturing solvents or harsh agitation techniques and encapsulated GM-CSF in a more stable precipitated form. NP sizes were within 200 nm for enhanced permeability and retention (EPR) effect with negative zeta potentials, spherical morphology, and high entrapment efficiencies. The optimal formulation was identified by sustained release of approximately 70% of loaded GM-CSF over 24 h, alongside an average size of 143 ± 35 nm and entrapment efficiency of 84 ± 5%. These NPs were successfully freeze-dried in 5% (w/v) hydroxypropyl-ß-cyclodextrin for long-term storage and further characterized. Bioactivity of released GM-CSF was determined by observing GM-CSF receptor activation on murine monocytes and remained fully intact. NPs were not cytotoxic to murine bone marrow-derived macrophages (BMDMs) at concentrations up to 1 mg/mL as determined by MTT and trypan blue exclusion assays. Lastly, NP components generated no significant transcription of inflammation-regulating genes from BMDMs compared to IFNγ+LPS "M1" controls. This report lays the preliminary groundwork to validate in vivo studies with GM-CSF-loaded PLGA/PEG-PLGA NPs for tumor immunomodulation. Overall, these data suggest that in vivo delivery will be well tolerated.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/síntese química , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/síntese química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Composição de Medicamentos , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacocinética , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Poliésteres/administração & dosagem , Poliésteres/farmacocinética , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética
15.
J Labelled Comp Radiopharm ; 64(10): 385-402, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34157793

RESUMO

13 C-labelled ω-hydroxy-carboxylic acids HO213 C-(CH2 )n -CH2 OH or HO2 C-(CH2 )n -13 CH2 OH (n = 12, 16, 20, 28) with 13 C labels selectively introduced either at the carboxy group or at the primary alcohol function at the end of the hydrocarbon chain have been synthesized. Different synthetic strategies had to be applied depending on the position of the label, the chain length of the respective synthetic target and due to economic considerations. 13 C labels in general were introduced by nucleophilic substitution of a suitable leaving group with labelled potassium cyanide and subsequent hydrolysis of the nitriles to produce the corresponding labelled carboxy functions, which may also be reduced to give the labelled primary alcohol group. All new compounds are characterized by GC/MS, IR and NMR methods as well as by elemental analysis.


Assuntos
Isótopos de Carbono/química , Ácidos Carboxílicos/química , Poliésteres/síntese química
16.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064416

RESUMO

The objective of this study was to synthesize and characterize a set of biodegradable block copolymers based on TPGS-block-poly(ε-caprolactone) (TPGS-b-PCL) and to assess their self-assembled structures as a nanodelivery system for paclitaxel (PAX). The conjugation of PCL to TPGS was hypothesized to increase the stability and the drug solubilization characteristics of TPGS micelles. TPGS-b-PCL copolymer with various PCL/TPGS ratios were synthesized via ring opening bulk polymerization of ε-caprolactone using TPGS, with different molecular weights of PEG (1-5 kDa), as initiators and stannous octoate as a catalyst. The synthesized copolymers were characterized using 1H NMR, GPC, FTIR, XRD, and DSC. Assembly of block copolymers was achieved via the cosolvent evaporation method. The self-assembled structures were characterized for their size, polydispersity, and CMC using dynamic light scattering (DLS) technique. The results from the spectroscopic and thermal analyses confirmed the successful synthesis of the copolymers. Only copolymers that consisted of TPGS with PEG molecular weights ≥ 2000 Da were able to self-assemble and form nanocarriers of ≤200 nm in diameter. Moreover, TPGS2000-b-PCL4000, TPGS3500-b-PCL7000, and TPGS5000-b-PCL15000 micelles enhanced the aqueous solubility of PAX from 0.3 µg/mL up to 88.4 ug/mL in TPGS5000-b-PCL15000. Of the abovementioned micellar formulations, TPGS5000-b-PCL15000 showed the slowest in vitro release of PAX. Specifically, the PAX-loaded TPGS5000-b-PCL15000 micellar formulation showed less than 10% drug release within the first 12 h, and around 36% cumulative drug release within 72 h compared to 61% and 100% PAX release, respectively, from the commercially available formulation (Ebetaxel®) at the same time points. Our results point to a great potential for TPGS-b-PCL micelles to efficiently solubilize and control the release of PAX.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/farmacologia , Poliésteres/química , Vitamina E/química , Varredura Diferencial de Calorimetria , Cromatografia em Gel , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Micelas , Nanopartículas/ultraestrutura , Tamanho da Partícula , Poliésteres/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina E/síntese química , Água/química , Difração de Raios X
17.
AAPS PharmSciTech ; 22(5): 174, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34114068

RESUMO

Posterior eye diseases are a common cause of vision problems in developing countries, which have encouraged the development of new treatment models for these degenerative diseases. Intraocular implants are one of the drug delivery systems to the posterior region of the eye. Using these implants, the blood-eye barrier can be bypassed; the complications caused by repeated in vitro administrations can be eliminated, and smaller amounts of the drug would be used during the treatment process. Meanwhile, biodegradable implants have received more attention due to their biodegradable structure and the lack of need for re-surgery to remove the rest of the system from the eye. The aim of this study is to employ biodegradable implants composed of polyethylene glycol (PEG) and 3-hydroxybutyrate-co-3-hydroxyvalerat (PHBV) to deliver betamethasone to the back of the eye in the treatment of retinopathy. PHBV polymer has been selected as the main polymer with a certain ratio of drug to polymer for fabrication of enamel and different amounts of PEG with three molecular weights used as pore generators to control drug release over a period of time. Based on the analysis of the results of differential scanning calorimetry (DSC) and FTIR spectroscopy, none of the polymers were degraded in the temperature range of the manufacturing process, and among betamethasone derivatives, the best option for implant preparation is the use of its basic form. Drug release studies over a period of three months showed that implants containing PHBV HV2% and PEG 6000 had a more appropriate release profile.


Assuntos
Implantes Absorvíveis , Betametasona/farmacocinética , Desenho de Fármacos , Poliésteres/farmacocinética , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacocinética , Betametasona/análogos & derivados , Betametasona/síntese química , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Implantes de Medicamento , Liberação Controlada de Fármacos , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Polietilenoglicóis/farmacocinética
18.
Angew Chem Int Ed Engl ; 60(32): 17629-17637, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34036695

RESUMO

Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co-encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Plásticos Biodegradáveis/farmacologia , Corantes Fluorescentes/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Poliésteres/farmacologia , Polietilenoglicóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/efeitos da radiação , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/efeitos da radiação , Compostos de Boro/síntese química , Compostos de Boro/farmacologia , Compostos de Boro/efeitos da radiação , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Humanos , Luz , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Poliésteres/síntese química , Poliésteres/efeitos da radiação , Polietilenoglicóis/síntese química , Polietilenoglicóis/efeitos da radiação , Compostos de Piridínio/síntese química , Compostos de Piridínio/farmacologia , Compostos de Piridínio/efeitos da radiação
19.
J Biomed Mater Res A ; 109(10): 1881-1892, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33871170

RESUMO

To understand the effect of mechanical stimulation on cell response, bone marrow stromal cells were cultured on electrospun scaffolds under two distinct mechanical conditions (static and dynamic). Comparison between initial and final mechanical and biological properties of the cell-constructs were conducted over 14 days for both culturing conditions. As a result, mechanically stimulated constructs, in contrast to their static counterparts, showed evident mechanical-induced cell orientation, an effective aligned collagen and tenomodulin extracellular matrix. This orientation provides clues on the importance of mechanical stimulation to induce a tendon-like differentiation. In addition, cell and collagen orientation lead to enhanced storage modulus observed under dynamic stimulation. Altogether mechanical stimulation lead to (a) cell and matrix orientation through the sense of the stretch and (b) a dominant elastic response in the cell-constructs with a minor contribution of the viscosity in the global mechanical behavior. Such a correlation could help in further studies to better understand the effect of mechanical stimulation in tissue engineering.


Assuntos
Estresse Mecânico , Tendões/fisiologia , Engenharia Tecidual , Animais , Fenômenos Biomecânicos , Proliferação de Células , Matriz Extracelular/metabolismo , Hidroxiprolina/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Poliésteres/síntese química , Poliésteres/química , Ratos Sprague-Dawley , Tecidos Suporte/química
20.
Molecules ; 26(7)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810558

RESUMO

In this study, new biodegradable and biocompatible amphiphilic polymers were obtained by modifying the peripheral hydroxyl groups of branched polyethers and polyesters with organosilicon substituents. The structures of the synthesized polymers were confirmed by NMR and GPC. Organosilicon moieties of the polymers were formed by silatranes and trimethylsilyl blocks and displayed hydrophilic and hydrophobic properties, respectively. The effect of the ratio of hydrophilic to hydrophobic organosilicon structures on the surface activity and biological activity of macromolecules was studied, together with the effect on these activities of the macromolecules' molecular weight and chemical structure. In particular, the critical micelle concentrations were determined, the effect of the structure of the polymers on their wetting with aqueous solutions on glass and parafilm was described, and the aggregation stability of emulsions was studied. Finally, the effect of the polymer structures on their antifungal activity and seed germination stimulation was examined.


Assuntos
Antifúngicos , Ascomicetos/efeitos dos fármacos , Materiais Biocompatíveis , Compostos Bicíclicos Heterocíclicos com Pontes , Compostos de Organossilício , Poliésteres , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Micelas , Estrutura Molecular , Compostos de Organossilício/síntese química , Compostos de Organossilício/química , Poliésteres/síntese química , Poliésteres/química
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