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2.
Chem Commun (Camb) ; 55(58): 8434-8437, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31259350

RESUMO

Phosphatidylcholine is the main component of liposomes and other phospholipid-based nanocarriers in drug delivery. However, the functions and applications of these nanocarriers are extremely limited by conventional phospholipids. Here we report novel disulfide phosphatidylcholines (SS-PCs) and SS-PC based liposomes (SS-LPs) used as alternatives to traditional phospholipids and liposomes.


Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Lipossomos/química , Fosfatidilcolinas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Dissulfetos/síntese química , Dissulfetos/metabolismo , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Humanos , Lipossomos/síntese química , Lipossomos/metabolismo , Camundongos , Oxirredução , Fosfatidilcolinas/síntese química , Fosfatidilcolinas/metabolismo
4.
Chem Soc Rev ; 48(11): 2967-3014, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31089607

RESUMO

Brain cancer, especially the most common type of glioblastoma, is highly invasive and known as one of the most devastating and deadly neoplasms. Despite surgical and medical advances, the prognosis for most brain cancer patients remains dismal and the median survival rarely exceeds 16 months. Drug delivery to the brain is significantly hindered by the existence of the blood-brain barrier (BBB), which serves as a protective semi-permeable membrane for the central nervous system. Recent breakthroughs in nanotechnology have yielded multifunctional theranostic nanoplatforms with the ability to cross or bypass the BBB, enabling accurate diagnosis and effective treatment of brain tumours. Herein, we make our efforts to present a comprehensive review on the latest remarkable advances in BBB-crossing nanotechnology, with an emphasis on the judicious design of multifunctional nanoplatforms for effective BBB penetration, efficient tumour accumulation, precise tumour imaging, and significant tumour inhibition of brain cancer. The detailed elucidation of BBB-crossing nanotechnology in this review is anticipated to attract broad interest from researchers in diverse fields to participate in the establishment of powerful BBB-crossing nanoplatforms for highly efficient brain cancer theranostics.


Assuntos
Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/terapia , Portadores de Fármacos/metabolismo , Glioblastoma/terapia , Nanopartículas/metabolismo , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanotecnologia/métodos
5.
Carbohydr Polym ; 216: 332-342, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047074

RESUMO

Chitosan has received a lot of attention as a carrier for small interfering RNA (siRNA), due to its capacity for complexation and intracellular release of these molecules. However, one of its limitations is its insolubility at neutral pH and the tendency towards aggregation of its nanoparticles in isotonic ionic strength. In this study, a series of amphipathic chitosans were synthesized by varying the degree of acetylation (DA) from ˜2 to ˜30 mol% and the degree of substitution (DS) from 5 to 25%. by tertiary amino groups (DEAE) The results showed that the adjustment of these parameters decreases the interparticle interactions mediated by hydrogen bonding to obtain nanoparticles with improved colloidal stability. siRNA-containing nanoparticles of 100 to 150 nm with low polydispersities (0.15-0.2) and slightly positive zeta potentials (˜+ 5 mV) were resistant to aggregation at pH 7.4 and ionic strength of 150 mM. This resistance to aggregation is provided by changes on the nanoparticle surface and highlights the importance of more organized self-assembly in providing colloidal stability at physiological conditions. Additionally, the PEGylation of the most promising vectors conferred favorable physicochemical properties to nanoparticles. The chitosans and their nanoparticles exhibited low toxicity and an efficient cell uptake, as probed by confocal microscopy of rhodamine labeled vectors. The results provide a new approach to overcome the limited stability of chitosan nanoparticles at physiological conditions and show the potential of these amphipathic chitosans as siRNA carriers.


Assuntos
Quitosana/análogos & derivados , Portadores de Fármacos/química , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Tensoativos/química , Anidridos Acéticos/química , Acetilação , Animais , Quitosana/síntese química , Quitosana/metabolismo , Quitosana/toxicidade , Dietilaminas/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Fluorescência , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Camundongos , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoglicóis/toxicidade , Células RAW 264.7 , RNA Interferente Pequeno/química , Rodaminas/química , Tensoativos/síntese química , Tensoativos/metabolismo , Tensoativos/toxicidade
6.
AAPS PharmSciTech ; 20(4): 162, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30989451

RESUMO

All-trans retinoic acid (ATRA) has been regarded as a wonder drug for many dermatological complications; however, its application is limited due to the extreme irritation, and toxicity seen once it has sufficiently concentrated into the bloodstream from the skin. Thus, the present study was aimed to increase the entrapment of ATRA and minimize its transdermal permeation. ATRA incorporated within nanostructured lipid carriers (NLCs) were produced by a green and facile thin lipid-film based microwave-assisted rapid technique (MART). The optimization was carried out using the response surface methodology (RSM)-driven artificial neural network (ANN) coupled with genetic algorithm (GA). The liquid lipid and surfactants were seen to play a very crucial role culminating in the particle size (< 70 nm), zeta potential (< - 32 mV), and entrapment of ATRA (> 98%). ANN-GA-optimized NLCs required a minimal quantity of the surfactants, formed within 2 min and were stable for 1 year at different storage conditions. The optimized NLC-loaded creams showed a skin retention (ex vivo) to an extent of 87.42% with no detectable drug in the receptor fluid (24 h) in comparison to the marketed cream which released 47.32% (12 h) of ATRA. The results were in good correlation with the in vivo skin deposition studies. The NLCs were biocompatible and non-skin irritant based on the primary irritation index. In conclusion, the NLCs were seen to have a very high potential in overcoming the drawbacks of ATRA for dermal delivery and could be produced conveniently by the MART.


Assuntos
Portadores de Fármacos , Lipídeos , Nanoestruturas , Administração Cutânea , Portadores de Fármacos/metabolismo , Micro-Ondas , Nanoestruturas/administração & dosagem , Tamanho da Partícula , Pele/metabolismo , Absorção Cutânea , Tretinoína
7.
J Mater Sci Mater Med ; 30(4): 47, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30980130

RESUMO

The objective of this study was to fabricate and characterize chitosan combined with different amounts of simvastatin-loaded nanoparticles and to investigate their potential for guided bone regeneration in vitro and in vivo. Different SIM-CSN formulations were combined into a chitosan scaffold (SIM-CSNs-S), and the morphology, simvastatin release profile, and effect on cell proliferation and differentiation were investigated. For in vivo experiments, ectopic osteogenesis and the critical-size cranial defect model in SD rats were chosen to evaluate bone regeneration potential. All three SIM-CSNs-S formulations had a porous structure and exhibited sustained simvastatin release. CSNs-S showed excellent degradation and biocompatibility characteristics. The 4 mg SIM-CSNs-S formulation stimulated higher BMSC ALP activity levels, demonstrated significantly earlier collagen enhancement, and led to faster bone regeneration than the other formulations. SIM-CSNs-S should have a significant effect on bone regeneration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Regeneração Tecidual Guiada/métodos , Nanopartículas/química , Nanopartículas/metabolismo , Sinvastatina/farmacocinética , Tecidos Suporte/química , Animais , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/metabolismo , Preparações de Ação Retardada , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Composição de Medicamentos , Masculino , Teste de Materiais , Microesferas , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley , Sinvastatina/administração & dosagem , Propriedades de Superfície , Engenharia Tecidual/métodos
8.
Artif Cells Nanomed Biotechnol ; 47(1): 1312-1320, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30987439

RESUMO

Hearing loss is the most common neurosensory impairment worldwide. While conductive hearing loss can be managed by surgery, the management of sensorineural hearing loss (SNHL), related to the damage of sensory cells of the inner ear is more challenging to manage medically. Many causes of SNHL such as sudden idiopathic SNHL, Meniere's disease, noise-induced hearing loss, autoimmune hearing loss or hearing loss from exposure to ototoxic substances can benefit from delivery of otoprotective drugs to the inner ear. However, systemic drug delivery through oral, intravenous and intramuscular methods leads to undesirable side effects due to the inner ear's limited blood supply and the relatively poor penetration of the blood-inner ear barrier (BLB). Therefore, there has been an increased interest for the targeted drug delivery to the inner ear using nanoparticles. Drug delivery through nanoparticles offers several advantages including drug stabilization for controlled release and surface modification for specific targeting. Understanding the biocompatibility of nanoparticles with cochlea and developing novel non-invasive delivery methods will promote the translation of nanoparticle-mediated drug delivery for auditory disorders from bench to bedside.


Assuntos
Portadores de Fármacos , Orelha Interna/metabolismo , Nanopartículas , Portadores de Fármacos/metabolismo , Endossomos/metabolismo , Perda Auditiva/tratamento farmacológico , Perda Auditiva/metabolismo , Humanos
9.
Int J Mol Sci ; 20(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022913

RESUMO

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the enzyme iduronate 2-sulfatase (IDS), which leads to the accumulation of glycosaminoglycans in most organ-systems, including the brain, and resulting in neurological involvement in about two-thirds of the patients. The main treatment is represented by a weekly infusion of the functional enzyme, which cannot cross the blood-brain barrier and reach the central nervous system. In this study, a tailored nanomedicine approach based on brain-targeted polymeric nanoparticles (g7-NPs), loaded with the therapeutic enzyme, was exploited. Fibroblasts from MPSII patients were treated for 7 days with NPs loaded with the IDS enzyme; an induced IDS activity like the one detected in healthy cells was measured, together with a reduction of GAG content to non-pathological levels. An in vivo short-term study in MPSII mice was performed by weekly administration of g7-NPs-IDS. Biochemical, histological, and immunohistochemical evaluations of liver and brain were performed. The 6-weeks treatment produced a significant reduction of GAG deposits in liver and brain tissues, as well as a reduction of some neurological and inflammatory markers (i.e., LAMP2, CD68, GFAP), highlighting a general improvement of the brain pathology. The g7-NPs-IDS approach allowed a brain-targeted enzyme replacement therapy. Based on these positive results, the future aim will be to optimize NP formulation further to gain a higher efficacy of the proposed approach.


Assuntos
Encéfalo/efeitos dos fármacos , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Iduronato Sulfatase/administração & dosagem , Mucopolissacaridose II/tratamento farmacológico , Nanopartículas/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Encéfalo/patologia , Portadores de Fármacos/química , Terapia de Reposição de Enzimas , Glicopeptídeos/química , Glicopeptídeos/metabolismo , Humanos , Iduronato Sulfatase/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucopolissacaridose II/enzimologia , Mucopolissacaridose II/metabolismo , Mucopolissacaridose II/patologia , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
10.
Int J Mol Sci ; 20(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991632

RESUMO

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Vesículas Extracelulares/química , Preparações Farmacêuticas/administração & dosagem , Animais , Portadores de Fármacos/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Lipossomos/química , Lipossomos/metabolismo , Plantas/química , Plantas/metabolismo , RNA Interferente Pequeno/administração & dosagem
11.
Carbohydr Polym ; 212: 215-221, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30832850

RESUMO

DrzBC and DrzBS (10-23 DNAzyme) could block the expression of HBV e- and s- gene respectively. But the application of 10-23 DNAzyme was limited owing to the lack of appropriate delivery vehicles. Chitosan oligosaccharide-SS-Octadecylamine (CSSO), a redox-responsive nano-sized polymeric carrier, could self-aggregate and bind with DNA by electrostatic interaction at proper mass ratio. Compared with the traditional commercial carrier Lipo2000, CSSO exhibited lower cytotoxicity, efficient cellular uptake by targeting cells, and rapidly DNA released in cytoplasm after escaping from endosomes. Including the same DNA concentration, Lipo2000/(DrzBC or DrzBS) showed maximum inhibitory rate on HBeAg (47.29 ±â€¯1.86%) and HBsAg (33.58 ±â€¯0.72%) secretion after 48 h incubation, and then both decreased. In contrast, HBeAg secretion inhibition by CSSO/DrzBC and HBsAg secretion inhibition by CSSO/DrzBS were up to 73.86 ±â€¯1.77% and 67.80 ±â€¯2.51% at 48 h, and further increased to 83.83 ±â€¯2.34% and 76.79 ±â€¯2.18% at 72 h, respectively. CSSO is a promising redox-responsive polymeric carrier for efficient anti-Hepatitis B Virus gene therapy.


Assuntos
Aminas/administração & dosagem , Quitosana/administração & dosagem , Terapia Genética/métodos , Vírus da Hepatite B/efeitos dos fármacos , Oligossacarídeos/administração & dosagem , Polímeros/administração & dosagem , Aminas/metabolismo , Quitosana/metabolismo , DNA Viral/efeitos dos fármacos , DNA Viral/genética , DNA Viral/metabolismo , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Células Hep G2 , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Humanos , Oligossacarídeos/metabolismo , Oxirredução/efeitos dos fármacos , Polímeros/metabolismo
12.
AAPS PharmSciTech ; 20(4): 152, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30911861

RESUMO

The current study is concerned with the development and characterization of mixed micelles intended for the dermal delivery of beclomethasone dipropionate, which is a topical corticosteroid used in the management of atopic dermatitis. Mixed micelles were prepared using thin-film hydration technique, employing different concentrations of pluronic L121 with either poloxamer P84 or pluronic F127 with different surfactant mixture-to-drug ratios. The prepared formulae were characterized concerning entrapment efficiency, particle size, and zeta potential. Two formulae were chosen for ex vivo skin deposition studies: one formulated using pluronic L121/poloxamer P84 mixture while the other using pluronic L121/pluronic F127 mixture. The optimum formula with the highest dermal deposition was subjected to morphological examination and was formulated as hydroxypropyl methylcellulose hydrogel. The hydrogel was evaluated regarding viscosity and was subjected to ex vivo deposition study in comparison with the commercially available cream Beclozone®. In vivo histopathological study was conducted for both the hydrogel and Beclozone® in order to evaluate their healing efficiency. In vivo histopathological study results showed that the prepared hydrogel successfully treated sub-chronic dermatitis in an animal model within a shorter period of time compared to Beclozone®, resulting in better patient compliance and fewer side effects.


Assuntos
Beclometasona/administração & dosagem , Dermatite/tratamento farmacológico , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Hidrogéis/administração & dosagem , Micelas , Animais , Animais Recém-Nascidos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Beclometasona/química , Beclometasona/metabolismo , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Dermatite/metabolismo , Dermatite/patologia , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Hidrogéis/química , Hidrogéis/metabolismo , Masculino , Camundongos , Tamanho da Partícula , Ratos , Ratos Wistar , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Tensoativos/administração & dosagem , Tensoativos/química , Tensoativos/metabolismo
13.
Drug Deliv ; 26(1): 179-187, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30822158

RESUMO

Periodontal disease is a complex problem which often interrelates with several serious systemic diseases. However, the satisfactory clinical therapy has yet to be achieved. Herein, serum albumin microspheres containing minocycline and zinc oxide nanoparticals (ZnO NPs) were prepared and incorporated in a Carbopol 940® hydrogel. Compared with 2% minocycline ointment (Perio®), the hydrogel has shown obvious therapy effects and the ability of gingival tissue self-repairing. The serum albumin microspheres containing 0.06% of minocycline and 0.025% of ZnO NPs presented an average size of 139 ± 0.42 nm using electrophoretic light scattering (n = 3). Photomicrographs obtained by TEM showed homogeneous and spherical-shaped particles. The encapsulation efficiency was 99.99% for minocycline and the slow-release time was more than 72 h with pH-sensitive property. The in vitro skin adhesion experiment showed that the largest bioadhesive force is 0.35 N. Moreover, the hydrogel showed broad-spectrum antimicrobial and effective antibacterial ability when concentration of the ZnO NPs was over 0.2 µg/mL. The cell survival rates were more than 85% below 0.8 mg/L of ZnO NPs, which proved its low toxicity and high security.


Assuntos
Hidrogéis/síntese química , Minociclina/síntese química , Nanopartículas/química , Periodontite/tratamento farmacológico , Albumina Sérica/síntese química , Óxido de Zinco/síntese química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Antibacterianos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Gengiva/patologia , Hidrogéis/administração & dosagem , Hidrogéis/metabolismo , Masculino , Minociclina/administração & dosagem , Minociclina/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Periodontite/metabolismo , Periodontite/patologia , Ratos , Ratos Sprague-Dawley , Albumina Sérica/administração & dosagem , Albumina Sérica/metabolismo , Óxido de Zinco/administração & dosagem , Óxido de Zinco/metabolismo
14.
Drug Deliv ; 26(1): 208-215, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30835582

RESUMO

Cisplatin is the most commonly used antitumor drug in the chemotherapy of a variety of malignancies. However, the severe side effects and drug resistance limit its clinical application. The aim of this study was to develop PLGA-based cisplatin-loaded implants and evaluate the antitumor efficacy of continuous intratumoral chemotherapy with the implants. The cisplatin-loaded implants were prepared by the direct compression method and characterized regarding drug content, micromorphology, in vitro and in vivo drug release profiles. Furthermore, the antitumor activity of the implants was conducted in sarcoma 180 tumor-bearing mice. The SEM images showed smooth surface of the implants and the mean drug content of the tested implants was (37.7% ± 0.5%, w/w). Both in vitro and in vivo release profiles of the implants were characterized by initial burst release followed by the sustained-release of cisplatin. Intratumoral implantation of the cisplatin-loaded implants could effectively inhibit the tumor growth. Additionally, intratumoral chemotherapy with the implants significantly reduced the systemic toxicity compared with intravenous injection of cisplatin. It is worth noting that an increase in the dose of the implants led to a higher tumor suppression rate without additional systemic toxicity. These results demonstrated that cisplatin-loaded implants enhanced the antitumor efficacy and reduced the dose-related side effects in sarcoma 180 tumor-bearing mice.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Portadores de Fármacos/administração & dosagem , Implantes de Medicamento/administração & dosagem , Sarcoma 180/tratamento farmacológico , Animais , Antineoplásicos/metabolismo , Cisplatino/metabolismo , Portadores de Fármacos/metabolismo , Implantes de Medicamento/metabolismo , Liberação Controlada de Fármacos/efeitos dos fármacos , Liberação Controlada de Fármacos/fisiologia , Camundongos , Distribuição Aleatória , Sarcoma 180/metabolismo , Resultado do Tratamento , Células Tumorais Cultivadas
15.
Analyst ; 144(9): 3103-3110, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30920573

RESUMO

Receptor-targeted delivery systems have been proposed as means of concentrating therapeutic agents to improve therapeutic effects on disease sites and reduce side effects on normal issues. Herein, we synthesized biocompatible folic acid (FA)-functionalized DHE-modified TiP (TiP-PAH-DHE-FA) nanoparticles as a drug delivery system that possessed high drug loading capability and enhanced folate-receptor-mediated cellular uptake. Moreover, it also allowed drug effect evaluation based on the real-time monitoring of the fluorescence intensity of HE molecules that are triggered by intercellular ROS. This acquired drug delivery system provided a novel platform to integrate efficient cell-specific drug delivery with real-time monitoring of therapeutic efficacy.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Titânio/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Endocitose/fisiologia , Etídio/análogos & derivados , Etídio/química , Etídio/metabolismo , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Humanos , Células MCF-7 , Microscopia Confocal/métodos , Nanopartículas/metabolismo , Poliaminas/química , Poliaminas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Titânio/metabolismo
16.
Food Funct ; 10(4): 1826-1835, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874272

RESUMO

The influence of carrier oil type (corn, fish, or flaxseed oil) on the production, stability, and simulated gastrointestinal behavior of vitamin-fortified nanoemulsions was studied. The nanoemulsions were formulated using pea protein as an emulsifier since there is increasing interest in substituting artificial and animal-based food ingredients with natural plant-based alternatives. Lipid digestion and vitamin D3 bioaccessibility were measured when the nanoemulsions were subjected to a three-stage in vitro gastrointestinal tract: oral, gastric, and small intestinal. The majority of all three lipids were digested within the first few minutes in the simulated small intestine, with the corn oil nanoemulsions being digested faster than the fish or flaxseed oils. Moreover, a greater fraction of triglycerides were digested by the end of the small intestine for the corn oil than for the fish and flaxseed oils. For the different carrier oils, vitamin bioaccessibility was ranked: corn oil > flaxseed oil ≈ fish oil. These results suggest that monounsaturated-rich oils (such as corn oil) are better for encapsulating and delivering vitamin D3 than polyunsaturated-rich ones (such as flaxseed or fish oil). The insights gained here may aid in the formulation of more efficacious vitamin-fortified foods and beverages from plant-derived ingredients.


Assuntos
Colecalciferol/química , Colecalciferol/metabolismo , Óleo de Milho/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Óleos de Peixe/química , Óleo de Semente do Linho/química , Proteínas de Plantas/química , Disponibilidade Biológica , Óleo de Milho/metabolismo , Digestão , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/instrumentação , Emulsões/química , Emulsões/metabolismo , Óleos de Peixe/metabolismo , Alimentos Fortificados/análise , Humanos , Óleo de Semente do Linho/metabolismo , Nanoestruturas/química , Ervilhas/química , Proteínas de Plantas/metabolismo
17.
Proc Natl Acad Sci U S A ; 116(12): 5405-5410, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30833393

RESUMO

Biomimetic systems often exhibit striking designs well adapted to specific functions that have been inspiring the development of new technologies. Herein, we explored the remarkable ability of honey bees to catch and release large quantities of pollen grains. Hair spacing and height on bees are crucial for their ability to mechanically fix pollen grains. Inspired by this, we proposed the concept of a micropatterned surface for microparticle entrapment, featuring high-aspect-ratio elastic micropillars spaced to mimic the hairy surface of bees. The hypothesis was validated by investigating the ability of polydimethylsiloxane microfabricated patches to fix microparticles. The geometrical arrangement, spacing, height, and flexibility of the fabricated micropillars, and the diameter of the microparticles, were investigated. Higher entrapment capability was found through the match between particle size and pillar spacing, being consistent with the observations that the diameter of pollen grains is similar to the spacing between hairs on bees' legs. Taller pillars permitted immobilization of higher quantities of particles, consistent with the high aspect ratio of bees' hairs. Our biomimetic surfaces were explored for their ability to fix solid microparticles for drug-release applications, using tetracycline hydrochloride as a model antibiotic. These surfaces allowed fixation of more than 20 mg/cm2 of antibiotic, about five times higher dose than commercialized patches (5.1 mg/cm2). Such bioinspired hairy surfaces could find applications in a variety of fields where dry fixation of high quantities of micrometer-sized objects are needed, including biomedicine, agriculture, biotechnology/chemical industry, and cleaning utensils.


Assuntos
Abelhas/ultraestrutura , Materiais Biomiméticos/metabolismo , Portadores de Fármacos/química , Polinização , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Portadores de Fármacos/metabolismo , Escherichia coli/efeitos dos fármacos , Pólen , Staphylococcus aureus/efeitos dos fármacos
18.
Biomater Sci ; 7(5): 1984-1994, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30834395

RESUMO

Zwitterionic complexes in aqueous solutions have been extensively explored as the most promising candidate in drug delivery systems for targeted cancer chemotherapy. A POSS-based supramolecular AD-POSS-(sulfobetaine)7/CD-PLLA zwitterionic complex has been fabricated via a combination of efficient click chemistry and host-guest interaction. The well-defined POSS-based zwitterionic polymer could self-assemble into spherical nanoparticles that encapsulated a model cancer drug (DOX) and exhibited drug release in a controlled manner in a faintly acidic environment. On account of the hydrophilic block with cationic and anionic groups in the microscopic range that can form a hydration layer via electrostatic interactions, these drug-loaded nanoparticles exhibited excellent stability in a tumor intracellular microenvironment or under other pH conditions as revealed by dynamic light scattering (DLS) and zeta potential measurements. In vitro experiments demonstrated that these POSS-based nanoparticles had high resistance to non-specific protein absorption and low cytotoxicity against normal cells. Moreover, these DOX-loaded aggregates could be accumulated and effectively internalized by HeLa and MCF-7 tumor cells, exhibiting effective cellular proliferation inhibition via the release of anticancer agents. Therefore, these POSS-based supramolecular amphiphilic zwitterionic complexes, relying on the simple supramolecular interaction and efficient click reaction, could further emerge as a potential universal anticancer drug nanocarrier system for multifunctional cancer chemotherapy.


Assuntos
Portadores de Fármacos/química , Interações Hidrofóbicas e Hidrofílicas , Compostos de Organossilício/química , Células 3T3 , Absorção Fisico-Química , Animais , Transporte Biológico , Bovinos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Teste de Materiais , Camundongos , Nanopartículas/química , Compostos de Organossilício/metabolismo , Compostos de Organossilício/toxicidade , Poliésteres/química , Soroalbumina Bovina/química
19.
Biomater Sci ; 7(5): 1888-1897, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30843539

RESUMO

Inefficient cytosolic delivery has limited the development of many promising biomacromolecular drugs, a long-standing challenge that has prompted extensive development of drug carriers that facilitate endosomal escape. Although many such carriers have shown considerable promise for cytosolic delivery of a diversity of therapeutics, the rupture or destabilization of endo/lysosomal membranes has also been associated with activation of the inflammasome with attendant risk of inflammation and toxicity. In this study, we investigated relationships between pH-dependent membrane destabilization, cytosolic drug delivery, and inflammasome activation using a series of well-defined poly[(ethylene glycol)-block-[(2-(dimethylamino)ethyl methacrylate)-co-(butyl methacrylate)] copolymers of variable second block composition and pH-responsive properties. We found that polymers that demonstrated the most potent membrane-destabilizing activity at early endosomal pH values in an erythrocyte hemolysis assay were most efficient at delivery of siRNA, yet tended to be associated with the least amount of NOD-like related protein 3 (NLRP3) inflammasome activation. By contrast, polymers that displayed minimal hemolysis activity and poor siRNA knockdown, and instead mediated lysosomal rupture likely due to a proton sponge mechanism, strongly induced NLPR3 inflammasome activation in a caspase- and cathepsin-dependent manner. Collectively, these findings reinforce the importance of early endosomal escape in minimizing inflammasome activation and also demonstrate the ability to tune the degree inflammasome activation via control of polymer structure with potential implications for design of vaccine adjuvants and immunotherapeutics.


Assuntos
Citosol/metabolismo , Portadores de Fármacos/química , Endossomos/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Polímeros/química , Linhagem Celular , Membrana Celular/metabolismo , Portadores de Fármacos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Polímeros/metabolismo
20.
Biomater Sci ; 7(5): 1825-1832, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30892297

RESUMO

As drug-delivery carriers for cancer chemotherapy, gatekeeper-capped mesoporous silica nanoparticles (MSNs) have been widely studied due to their high drug-loading capability, controlled drug release property and good biocompatibility. However, the currently reported gatekeeper-capped MSNs suffer from complex synthetic procedures, potential toxicity of gatekeepers, unsatisfactory control on drug stimuli-release, etc. In this work, we develop a simple but efficient approach to fabricate PEGylated organosilica-capped mesoporous silica nanoparticles (POMSNs) by employing a disulfide-doped organosilica coating as the gatekeeper formed by the hydrolysis and condensation of a silane coupling agent 3-(mercaptopropyl)trimethoxysilane (MPTMS) to block the mesopores of MSNs. Owing to the glutathione (GSH)-responsive biodegradation behavior of the disulfide-doped organosilica gatekeeper, the DOX-loaded POMSNs exhibit only 20% cell viability towards SMMC-7721 tumor cells, and almost no toxicity towards L-02 cells at a DOX concentration of 50 µg mL-1 was measured, demonstrating their selective cytotoxicity in vitro. More importantly, it is demonstrated that the DOX-loaded POMSNs exhibit a tumor inhibition rate of 71.3% and negligible systematic toxicity. Consequently, the resultant POMSNs show great potential as drug nanocarriers for redox-responsive drug release and passive-targeting tumor chemotherapy.


Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Nanoestruturas/química , Dióxido de Silício/química , Dióxido de Silício/síntese química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Técnicas de Química Sintética , Doxorrubicina/química , Doxorrubicina/metabolismo , Portadores de Fármacos/metabolismo , Feminino , Glutationa/metabolismo , Humanos , Espaço Intracelular/metabolismo , Camundongos , Oxirredução , Porosidade , Dióxido de Silício/metabolismo
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