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1.
Bioresour Technol ; 327: 124796, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33561792

RESUMO

This paper studied the effect of thermal-alkali with rhamnolipid coupling pretreatment waste activated sludge (WAS) on the dissolution and acid production of organic matter. The results showed that when the dosage of rhamnolipid (RL) was 40 mg/g vs, the dissolution rate of soluble Chemical oxygen demand (SCOD) and soluble carbohydrate (SC) was the highest, and the concentration of soluble protein (SP), biopolymer and neutral low molecular substances was the highest. Three-dimensional fluorescence parallel factor analysis found that the addition of rhamnolipid promoted the formation of fulvic acids. When the dosage of rhamnolipid was 60 mg/g vs, the highest peak concentration of volatile fatty acids (VFAs) reached 3.5 days. The type of fermentation acid was butyric acid. The higher cracking rate and higher acid production rate showed that thermal-alkali with rhamnolipid had better acid production performance than thermal-alkali pretreatment sludge, but the amount of rhamnolipid affected the fermentation type.

2.
Molecules ; 26(2)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477555

RESUMO

13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood-brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats' plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15-30 nm), positive charge (5-9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2-6-fold and 1.3-7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.

3.
Antonie Van Leeuwenhoek ; 114(3): 225-233, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33400070

RESUMO

A Gram-stain-negative, non-spore-forming, non-motile, short-rod-shaped, and aerobic bacterial strain (designated L72T) was isolated from propylene oxide saponification wastewater activated sludge obtained from a wastewater treatment facility in Binzhou (Shandong Province, PR China). Strain L72T grew between 25 and 40 °C (optimum growth at 30 °C). The pH range for growth was between 6.0 and 8.0 (optimum growth at pH 7.0). The range of NaCl concentrations for the growth of strain L72T was 0-3.0 % (w/v), with optimum growth at 1.0-2.0 % (w/v). The major cellular fatty acids of strain L72T were C19:0cyclo ω8c, C18:1ω7c, iso-C15:0, and anteiso-C15:0. Strain L72T contained Q-10 as the predominant respiratory quinone. The polar lipid profile was composed of Phosphatidylcholine, Glycolipid, Aminophospholipid, Phosphatidylethanolamine, Phosphatidylserine, Phosphatidyldimethylethanolamine, one unknown lipid (L) and two unidentified Phospholipids (PL). Genome sequencing revealed a genome size of 4,703,686 bp and a G + C content of 69.0 mol%. The 16S rRNA gene sequence similarities of strain L72T with other species were less than 94%. Phylogenetic analyses based on 16S rRNA gene sequences and genome data, revealed that strain L72T formed a distinct phylogenetic lineage within the order Hyphomicrobiales, separating them from members of all families. Strain L72T showed 70.7% average nucleotide identity and 18.6% digital DNA-DNA hybridization identity with the closely related species Rhodoligotrophos defluvii. Based on the phenotypic, phylogenetic and chemotaxonomic data, a new family Propylenellaceae fam. nov. comprising the genus Propylenella gen. nov. and species Propylenella binzhouense sp. nov. is proposed. The type strain is L72T (=  CCTCC AB 2019081T  =  KCTC 72254T).

4.
Artigo em Inglês | MEDLINE | ID: mdl-33288708

RESUMO

Leafy head is a unique type of plant architecture found in some vegetable crops, with leaves bending inward to form a compact head. The genetic and molecular mechanisms underlying leafy head in vegetables remain poorly understood. We genetically fine-mapped and cloned a major quantitative trait locus controlling heading in lettuce. The candidate gene (LsKN1) is a homolog of knotted 1 (KN1) from Zea mays Complementation and CRISPR/Cas9 knockout experiments confirmed the role of LsKN1 in heading. In heading lettuce, there is a CACTA-like transposon inserted into the first exon of LsKN1 (LsKN1▽). The transposon sequences act as a promoter rather than an enhancer and drive high expression of LsKN1▽. The enhanced expression of LsKN1▽ is necessary but not sufficient for heading in lettuce. Data from ChIP-sequencing, electrophoretic mobility shift assays, and dual luciferase assays indicate that the LsKN1▽ protein binds the promoter of LsAS1 and down-regulates its expression to alter leaf dorsoventrality. This study provides insight into plant leaf development and will be useful for studies on heading in other vegetable crops.

5.
Int J Nanomedicine ; 15: 10385-10399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376327

RESUMO

Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers, and so on. In this review, we aim to offer a summary of chemical structure and properties, anti-cancer activities, drug delivery systems and combination therapy of GA, which might provide a reference to promote the development and clinical application of GA.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Xantonas/administração & dosagem , Xantonas/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Garcinia/química , Humanos , Micelas , Nanoestruturas , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/tratamento farmacológico , Xantonas/química
6.
Int J Nanomedicine ; 15: 10435-10451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380794

RESUMO

Purpose: Nose-to-brain drug delivery is an effective approach for poorly soluble drugs to bypass the blood-brain barrier. A new drug intranasal delivery system, a nanosuspension-based in situ gel, was developed and evaluated to improve the solubility and bioavailability of the drug and to prolong its retention time in the nasal cavity. Materials and Methods: Breviscapine (BRE) was chosen as the model drug. BRE nanosuspensions (BRE-NS) were converted into BRE nanosuspension powders (BRE-NP). A BRE nanosuspension in situ gelling system (BRE-NG) was prepared by mixing BRE-NP and 0.5% gellan gum (m/v). First, the BRE-NP were evaluated in terms of particle size and by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Subsequently, the critical ionic concentration of the gellan gum phase transition, influence of the deacetylated gellan gum (DGG) concentration on the expansion coefficient (S%), water-holding capacity, rheological properties and in vitro release behaviour of the BRE-NG were investigated. The pharmacokinetics and brain distribution of the BRE-NG after intranasal administration were compared with those of the intravenously injected BRE-NP nanosuspensions in rats. Results: The rheology results demonstrated that BRE-NG was a non-Newtonian fluid with good spreadability and bioadhesion performance. Moreover, the absolute bioavailability estimated for BRE-NG after intranasal administration was 57.12%. The drug targeting efficiency (DTE%) of BRE in the cerebrum, cerebellum and olfactory bulb was 4006, 999 and 3290, respectively. The nose-to-brain direct transport percentage (DTP%) of the cerebrum, cerebellum and olfactory bulb was 0.975, 0.950 and 0.970, respectively. Conclusion: It was concluded that the in situ gel significantly increased the drug retention time at the administration site. Therefore, the nanosuspension-based in situ gel could be a convenient and effective intranasal formulation for the administration of BRE.


Assuntos
Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Flavonoides/administração & dosagem , Flavonoides/farmacocinética , Nanoestruturas/administração & dosagem , Administração Intranasal , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Géis/administração & dosagem , Masculino , Nanoestruturas/química , Tamanho da Partícula , Polissacarídeos Bacterianos/química , Polissorbatos/química , Ratos Sprague-Dawley , Reologia , Solubilidade , Difração de Raios X
7.
Biomed Pharmacother ; 133: 110917, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217688

RESUMO

Scutellaria baicalensis Georgi., a plant used in traditional Chinese medicine, has multiple biological activities, including anti-inflammatory, antiviral, antitumor, antioxidant, and antibacterial effects, and can be used to treat respiratory tract infections, pneumonia, colitis, hepatitis, and allergic diseases. The main active substances of S. baicalensis, baicalein, baicalin, wogonin, wogonoside, and oroxylin A, can act directly on immune cells such as lymphocytes, macrophages, mast cells, dendritic cells, monocytes, and neutrophils, and inhibit the production of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α, and other inflammatory mediators such as nitric oxide, prostaglandins, leukotrienes, and reactive oxygen species. The molecular mechanisms underlying the immunomodulatory and anti-inflammatory effects of the active compounds of S. baicalensis include downregulation of toll-like receptors, activation of the Nrf2 and PPAR signaling pathways, and inhibition of the nuclear thioredoxin system and inflammation-associated pathways such as those of MAPK, Akt, NFκB, and JAK-STAT. Given that in addition to the downregulation of cytokine production, the active constituents of S. baicalensis also have antiviral and antibacterial effects, they may be more promising candidate therapeutics for the prevention of infection-related cytokine storms than are drugs having only antimicrobial or anti-inflammatory activities.

8.
Food Sci Nutr ; 8(10): 5402-5409, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33133542

RESUMO

To satisfy the demand of industrial production, selecting strains suitable for fermentation initiation is necessary. In this study, the effects of mixed-starter culture including Leuconostoc, Lactobacillus, and Weissella on the quality of Sichuan pickle were discussed. Results showed that mixed-starter culture can accelerate fermentation and had the highest efficiency for nitrite degradation, that is, the maximum nitrite concentration was 8.97 g/kg on day 1 and decreased to 1.88 mg/kg after 3 days. The mixed-starter culture improved the sensory properties of pickles, which easily produced acids but had reduced amounts of total acids. The pickle products fermented by the mixed-starter culture contained increased lactic acid (17.52 g/kg), mannitol (0.62%), umami (35.85), and sweet (11.36) amino acids on day 4. The strains Weissella paramesenteroides C2-2 and Lactobacillus brevis ZP11-2 grew well in the mixed-starter culture fermentation.

9.
Huan Jing Ke Xue ; 41(9): 4322-4332, 2020 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124314

RESUMO

Immobilization of bacteria on biochar can improve the performance of the soil complex polluted with cadmium (Cd) and arsenic (As). In this study, bacteria (Delftia sp. B9, B9), biochar (corn stalks biochar, CSB), and biochar-bacteria complexes (B-CSB) were used as adsorption materials to explore the adsorption characteristics of Cd and As. The effects of pH on the adsorption performance of Cd and As and the ion removal from the aqueous solution were investigated, and the adsorption behaviors were simulated using an isothermal adsorption model. The changes in Cd and As speciation with the addition of B9, CSB, and B-CSB to As and Cd-contaminated soil were explored. The results showed that the Cd-saturated adsorption capacities of B9, CSB, and B-CSB were 49.43, 82.68, and 75.38 mg ·g-1, respectively; the As-saturated adsorption capacities were 24.67, 42.92, and 34.03 mg ·g-1, respectively. The concentration of available Cd and As significantly decreased, whereas the residual fraction increased after the addition of B-CSB. B-CSB was shown to be an effective material for the remediation of soil complexes polluted with Cd and As.


Assuntos
Arsênico , Poluentes do Solo , Adsorção , Cádmio , Carvão Vegetal , Solo , Poluentes do Solo/análise , Zea mays
10.
Differentiation ; 116: 9-15, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33080410

RESUMO

BACKGROUND: Congenital hypospadias is a common congenital malformation of the urinary system in male children. However, the role of circRNA in congenital hypospadias remains unknown. METHODS: Differentially expressed circRNAs and mRNAs were identified by RNA sequencing. GO and KEEG analysis were performed to uncover the key function and pathways. The interaction networks were constructed and analyzed by competing endogenous (ce)RNA analysis. Immunohistochemistry (IHC) and qRT-PCR were used to detect the expressions of androgen receptor (AR) and hsa_circ_0000417 in normal and hypospadias tissues. Further, the correlation between hsa_circ_0000417 and other clinical indicators were calculated. RESULTS: Compared with normal foreskin tissues, 1329 circRNAs and 978 mRNAs were significantly upregulated, 3176 circRNAs and 614 mRNAs were significantly downregulated in hypospadias tissues, respectively. MAPK and PI3K-Akt signaling pathways play important roles in congenital hypospadias. The expression of AR and hsa_circ_0000417 in 68 hypospadias tissues was significantly lower than that in 68 normal foreskin tissues (P < 0.05). The expression of the AR, as analyzed using IHC, was consistent with the qPCR results. A significant correlation was noted between the expression of AR and hsa_circ_0000417 in 68 clinical samples (P < 0.05). Furthermore, the expression level of hsa_circ_0000417 was associated with the incidence of other diseases and the location of the hypospadias site (P < 0.05). Expression of hsa_circ_0000417 was significantly downregulated in hypospadias patients without other diseases (P < 0.05). CONCLUSION: Hsa_circ_0000417 may regulate the expression of AR, and the expression of hsa_circ_0000417 in normal foreskin tissues is associated with the occurrence of hypospadias.

11.
Liver Cancer ; 9(5): 563-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33083281

RESUMO

Background: Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. Aims: The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. Methods: The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. Results: The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. Conclusions: The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.

12.
Taiwan J Ophthalmol ; 10(3): 208-211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33110753

RESUMO

PURPOSE: We introduce a novel technique for closed chamber iridodialysis repair. MATERIALS AND METHODS: We use a 2.8-mm paracentesis knife to penetrate into the anterior chamber and create interrupted incisions in the sclera. The wounds are 1.5 mm distant from the limbus, at consistent 2.8-mm intervals along the dialysis area. After injecting viscocohesive ophthalmic viscosurgical device through a side port to relieve the synechia and to push the iris toward the incisions, the iris is then grasped by Kelman forceps through the sclera, dragged carefully, and incarcerated. After adjusting the tension of the iris according to the pupil shape, the sclera and the incarcerated iris tissue were sutured together with 10-0 nylon. RESULTS: The technique was effective in six patients with traumatic iridodialysis. CONCLUSION: Our surgical technique repairs the iris, restores the shape of pupil, as well as avoids creating a large incision in the limbus in patients suffering from iridodialysis.

13.
Arch Microbiol ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037888

RESUMO

A novel Gram-strain-negative, beige-pigmented, aerobic, rod-shaped, non-flagellated and non-gliding bacterium, designated strain lm93T, was isolated from rhizosphere soil of Alhagi sparsifolia obtained from Alar city, located in Xinjiang province, China. Growth optimally occurred at 30 °C, pH 6.5-7.5, and 0-2% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain lm93T belonged to the genus Chelativorans, with highest sequence similarity to Chelativorans multitrophicus DSM 9103T (96.9%). Genome sequencing revealed a genome size of 5 689 708 bp and a G + C content of 64.3 mol%. The ANI, POCP and the dDDH between strain lm93T and C. multitrophicus DSM 9103T were 76.4%, 54.8% and 0.8%, respectively. The prediction result of secondary metabolites based on genome showed that the strain lm93T contained one cluster of bacteriocin, one cluster of terpene production, two clusters of ectoine production, one cluster of non-ribosomal peptide synthetase, one cluster of type I polyketide synthases, three clusters of homoserine lactone production, one cluster of N-acetylglutaminylglutamine amide production and one cluster of phosphonate production. The major respiratory quinone was Q-10. The major fatty acids were C19:0 cyclo ω8c, iso-C17:0 and summed feature 8 (C18:1 ω6c and/or C18:1 ω7c) and its polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified aminophospholipids, aminoglycolipid, three unknown lipids and diphosphatidylglycerol. On the basis of these data, strain lm93T is considered to represent a novel species of the genus Chelativorans, for which the name Chelativorans xinjiangense sp. nov. is proposed. The type strain is lm93T (= KCTC 72857T = CCTCC AB2019376T).

14.
Sci China Life Sci ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33009993

RESUMO

As a potential cancer immunotherapeutic agent, chlorogenic acid (CHA) has entered phase II clinical trials in China as a lyophilized powder formulation for treating glioma. However, the in vivo instability of CHA necessitates daily intramuscular injections, resulting in patient noncompliance. In this study, CHA-phospholipid complex (PC)-containing PEGylated liposomes (CHA-PC PEG-Lipo, named as CPPL), with CHA-PC as the drug intermediate, were prepared to lower the administration frequency. CPPL demonstrated excellent physicochemical properties, enhanced tumor accumulation, and inhibited tumor growth even when the administration interval was prolonged to 4 days when compared to a CHA solution and CHA-PC loaded liposomes (CHA-PC Lipo, labeled as CPL), both of which only demonstrated antitumor efficacy with once-daily administration. Further evaluation of the in vivo antitumor immune mechanism suggested that the extended antitumor immune efficacy of CPPL could be attributed to its distinct immune-stimulating mechanism when compared with CHA solution and CPL, such as stimulating both CD4+ and CD8+ T cell infiltration, inhibiting myeloid-derived suppressor cell expression, reducing the expression of Th2 related factors, and notably, increasing the memory T cells in tumor tissues. This CHA-containing formulation could reduce the frequency of in vivo CHA administration during cancer treatment via T cells, especially memory T cell regulation.

15.
Drug Discov Today ; 25(12): 2080-2088, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33017690

RESUMO

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

16.
Acta Pharm Sin B ; 10(8): 1576-1585, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963951

RESUMO

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

17.
Int J Nanomedicine ; 15: 5629-5643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801706

RESUMO

Purpose: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein. Methods: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein. Results: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation. Conclusion: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.


Assuntos
Flavanonas/administração & dosagem , Nanopartículas/administração & dosagem , Fosfolipídeos/química , Administração Cutânea , Animais , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Flavanonas/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Lecitinas/química , Masculino , Nanopartículas/efeitos adversos , Nanopartículas/química , Permeabilidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
18.
Front Plant Sci ; 11: 802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695125

RESUMO

Chromosome painting is one of the key technologies in cytogenetic research, which can accurately identify chromosomes or chromosome regions. Oligonucleotide (oligo) probes designed based on genome sequences have both flexibility and specificity, which would be ideal probes for fluorescence in situ hybridization (FISH) analysis of genome structure. In this study, the bulked oligos of the two arms of chromosome seven of cotton were developed based on the genome sequence of Gossypium raimondii (DD, 2n = 2× = 26), and each arm contains 12,544 oligos. Chromosome seven was easily identified in both D genome and AD genome cotton species using the bulked chromosome-specific painting probes. Together with 45S ribosomal DNA (rDNA) probe, the chromosome-specific painting probe was also successfully used to correct the chromosomal localization of 45S rDNA in G. raimondii. The study reveals that bulked oligos specific to a chromosome is a useful tool for chromosome painting in cotton.

19.
Bioact Mater ; 5(3): 694-708, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32478203

RESUMO

Tumor-associated macrophages (TAMs) generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis, suggesting their potential value as a target in cancer immunotherapy. Chlorogenic acid (CHA) has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype. However, rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials. In this study, mannosylated liposomes are developed for targeted delivery of CHA to TAMs. The immunoregulatory effects of CHA, along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes, are investigated through in vitro and in vivo experiments. The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size, favorable stability, and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects. Further, CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype. Overall, these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.

20.
Drug Deliv ; 27(1): 900-908, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32597266

RESUMO

Deformable nanovesicles (DNVs) have been used in the buccal delivery of biomacromolecules due to their ability to enhance drug penetration. However, no breakthroughs have been made until now due to limited understanding of the factors affecting in vivo buccal delivery. In this study, we designed a series of DNVs, based on an insulin-phospholipid complex (IPC-DNVs), to investigate the influence of drug dose, buccal administration methods, and key quality characteristics of IPC-DNVs for buccal delivery. IPC-DNVs showed a non-linear dose-response relationship between 8 and 12 IU. There was no significant effect of drug delivery site (sublingual mucosa/buccal mucosa) or ligation time (15 or 30 min) on buccal absorption of IPC-DNVs. However, the area above the curve of reduction in blood glucose level overtime (AAC0-6h) for oral mucosa administration was significantly higher than that for buccal mucosa administration. Increasing the drug concentration in IPC-DNVs led to a decrease in AAC0-6h. This might be due to local leakage of DNVs, while squeezing through biological barriers with high concentration of insulin, thus hindering the subsequent delivery of DNVs. IPC-DNVs, measuring 80-220 nm in size, did not significantly affect AAC0-6h. However, when the size was increased to approximately 400 nm, AAC0-6h decreased, thus suggesting that IPC-DNVs with reasonable size were more effective. Additionally, increased deformability of IPC-DNVs might cause drugs to leak easily, thus reducing the promoting effect of buccal absorption. Our results clarified the effect of characteristics of IPC-DNVs on buccal delivery in vivo and provided meaningful support for the design of dosage form of DNVs.

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