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1.
Int J Dent Hyg ; 19(3): 323-331, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33934498

RESUMEN

OBJECTIVES: This cross-sectional study examined the perceived quality of life (QOL) of Oral Health Therapy (OHT) students and compared the domain differences between Dental students, gender, and year-of-study. METHODS: OHT students from a local polytechnic were invited to participate (IRB no. (SHS-2019-001). Perceived QOL was assessed with the multidimensional World Health Organization QOL (WHOQOL)-BREF instrument. Demographic information and WHOQOL-BREF responses were collected electronically. Raw scores were converted to transformed scores and related to data of Dental students from other countries. Statistical analyses were performed with a T-test, one-way ANOVA/posthoc Tukey's test, and Pearson's correlation (p < 0.05). RESULTS: Of the total cohort of 66 students, 65 consented to participation (98.5% response rate). The study sample (mean age 19.2 ± 2.9 years) comprised of 83.1% females (54/65). Mean domain scores were as follows: Physical health - 54.90 ± 9.78; psychological - 50.98 ± 17.36; social relationships - 60.69 ± 16.47; and environment - 66.80 ± 13.66. The psychological domain was rated the lowest as with most other studies on Dental students. Mean scores for the overall perception of QOL and "satisfaction with health" (SWH) were 3.46 ± 0.83 and 3.35 ± 0.89 respectively. No significant difference in the domain and overall QOL/SWH scores were observed between genders. Psychological and environmental domains scores were significantly different between the first and third-year students (p ≤ 0.02). Correlations coefficients between the QOL domains ranged from rs  = 0.18-0.66. CONCLUSION: Aside from the USA and Saudi Arabia, the perceived QOL of Asian OHT students was generally comparable to those of Dental students from other countries. Overall perceived QOL and satisfaction with health were moderately favourable.


Asunto(s)
Comparación Transcultural , Calidad de Vida , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Salud Bucal , Arabia Saudita , Estudiantes de Odontología , Encuestas y Cuestionarios , Adulto Joven
2.
Oral Dis ; 26(5): 998-1009, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32144839

RESUMEN

OBJECTIVES: We aimed to investigate whether skeletal-specific H-type blood vessels exist in alveolar bone and how they function in alveolar bone remodeling. MATERIALS AND METHODS: H-type vessels with high expression of CD31 and Endomucin (CD31hi Emcnhi ) were immunostained in alveolar bone. Abundance and age-related changes in CD31hi Emcnhi endothelial cells (H-ECs) were detected by flow cytometry. Osteoprogenitors association with H-type vessels and bone mass were detected in tooth extraction model of alveolar bone remodeling by immunohistofluorescence and micro-CT, respectively. Transcription and expression of H-EC feature genes during in vitro Notch inhibition were measured by RT-qPCR and immunocytofluorescence. RESULTS: We verified that H-type vessels existed in alveolar bone, the abundance of which was highest at infancy age, then decreased but maintained a constant level during aging. In tooth extraction model, H-ECs significantly increased with concomitant perivascular accumulation of Runx2+ osteoprogenitors and gradually augmentation of bone mass. Notch inhibition of in vitro cultured H-ECs resulted in decreased expression levels of Emcn and hes1, but not Pecam1 or Kdr genes, with decreased expression levels of H-EC numbers, accordingly. CONCLUSIONS: The present study suggests that H-type vessels promote osteogenesis during alveolar bone remodeling. Notch signaling pathway regulates expression of Emcn and possibly determines fate and functions of alveolar H-ECs.


Asunto(s)
Remodelación Ósea , Células Endoteliales , Osteogénesis , Extracción Dental , Animales , Ratones , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética
3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(6): 735-741, 2020 Nov.
Artículo en Zh | MEDLINE | ID: mdl-33236593

RESUMEN

OBEJECTIVE: To investigate the role of a novel chemically defined medium (CDM) in the regulation of dental papilla cells (DPCs) functional phenotype in vitro and periodontal bone regeneration in vivo. METHODS: DPCs were isolated and cultured in conventional medium (CM) or CDM. The surface makers, and the proliferation, migration and osteogenic differentiation abilities of DPCs were evaluated. In vivo, the DPCs that mixed with collagen gel were implanted into the model rats in the defect of periodontal to repair the periodontal tissue. Regeneration of the tissues was examined by microcomputed tomography and histological observation. RESULTS: DPCs in the CM group and CDM group showed similar surface markers. Compared to the CM group, the CDM significantly enhanced the proliferation, colony-forming efficiency and migration of DPCs in vitro. In addition, real time PCR showed that the expression levels of osteogenesis-related genes, Runx2, Alp and Opn. were significantly enhanced in DPCs in the CDM group. DPCs cells treated with CDM also exhibited higher alkaline phosphatase activity and stronger ability of formation of mineralized nodules in vitro. In vivo, DPCs from CDM group significantly enhanced the periodontal bone regeneration and the reconstruction of periodontal bone tissues in rat periodontal defect model. CONCLUSION: CDM is a suitable medium to culture DPCs for periodontal bone regeneration. This research provided a substitute for basic research and set the stage for future clinical application of stem cell transplantation.


Asunto(s)
Osteogénesis , Ligamento Periodontal , Animales , Regeneración Ósea , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Papila Dental , Ratas , Regeneración , Microtomografía por Rayos X
4.
Mol Ther ; 25(7): 1567-1579, 2017 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-28274796

RESUMEN

The success of small interfering RNA (siRNA)-mediated gene silencing for cancer therapy is still limited because of its instability and poor intracellular internalization. Traditional cationic carriers cannot adequately meet the need for clinical application of siRNA. We herein report a dual-functional liposome containing a cholesterol derivative of metformin, i.e., LipoMET, which takes advantage of the fusogenic activity as well as intrinsic tumor apoptosis inducing ability of biguanide moiety to achieve a combinational anti-oncogenic effect. In this study, the vascular endothelial growth factor (VEGF)-specific siRNAs were first electrostatically condensed into a ternary nanocomplex composed of polycation and hyaluronate, which was subsequently enveloped by LipoMET through membrane fusion. In comparison with common cationic control group, the resulting envelope-type nanoparticles (PH@LipoMET nanoparticles [NPs]) showed the ability of rapid cellular internalization and effective endosomal escape of siRNA during intracellular trafficking studies. Systemic administration of the targeted LipoMETs was capable of inducing apoptosis and tumor growth inhibition in the NCI-H460 xenograft model. When carrying VEGF-specific siRNAs, PH@LipoMET NPs remarkably downregulated the expression of VEGF and led to even more tumor suppression in vivo. Thus, LipoMET originated envelope-type nanoparticles may serve as a potential dual-functional siRNA delivery system to improve therapeutic effect of oncogene silencing.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Regulación Neoplásica de la Expresión Génica , Liposomas/administración & dosificación , Neoplasias Pulmonares/terapia , Metformina/farmacología , ARN Interferente Pequeño/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Colesterol/química , Colesterol/metabolismo , Endosomas/metabolismo , Femenino , Humanos , Ácido Hialurónico/química , Ácido Hialurónico/metabolismo , Liposomas/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Metformina/análogos & derivados , Metformina/metabolismo , Ratones , Ratones Desnudos , ARN Interferente Pequeño/química , ARN Interferente Pequeño/metabolismo , Receptores sigma/genética , Receptores sigma/metabolismo , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
5.
World J Clin Cases ; 11(32): 7895-7899, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38073685

RESUMEN

BACKGROUND: Tardive dyskinesia (TD) is a serious and disabling movement disorder; it impairs social function and quality of life and increases the mortality rate. TD is usually induced by the use of antipsychotic drugs; however, the underlying mechanism remains unclear. Pharmacotherapy of TD includes cholinergic drugs, benzodiazepines, ginkgo biloba extract (GBE), antioxidants, amantadine, propanolol, botulinum toxin, valbenazine, and deutetrabenazine, whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy (MECT) and deep brain stimulation. We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine, clozapine, and MECT. CASE SUMMARY: A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution. Her TD symptoms did not resolve despite various treatments, such as GBE, vitamin E, trihexyphenidyl, promethazine, benzodiazepines, and switching to quetiapine and olanzapine. After admission, she was given deutetrabenazine 6 mg bid. Her buccal tremor was slightly resolved 3 d later; however, her tongue remained protruded and could not be retracted. Quetiapine was switched to clozapine on day 4, and the buccal tremor remarkably resolved, and the tongue could be retracted into the mouth from day 6 onward. After three sessions of MECT, the buccal tremor resolved further. Since then, she has been able to take a semifluid diet, and her quality of life improved remarkably during 6 mo of follow-up. CONCLUSION: TD is a serious condition which could be caused by antipsychotic medications; however, the best strategy against TD is prevention and monitoring during using antipsychotics. For patients with TD caused by antipsychotic medication use, multiple measures should be considered like switching to clozapine, adjunction with deutetrabenazine, or even MECT.

6.
Adv Healthc Mater ; 11(4): e2101504, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34784443

RESUMEN

Degradable hydrogel adhesives with multifunctional advantages are promising to be candidates as hemostatic agents, surgical sutures, and wound dressings. In this study, hydrogel adhesives are constructed by catechol-conjugated gelatin from natural resource, iron ions (Fe3+ ), and a synthetic polymer. Specifically, the latter is prepared by the radical ring-opening copolymerization of a cyclic ketene acetal monomer 5,6-benzo-2-methylene-1,3-dioxepane and N-(2-ethyl p-toluenesulfonate) maleimide. By the incorporation of ester bonds in the backbone and the combination with quaternary ammonium salt pendants in the polymer, it exhibits excellent degradability and antibacterial property. Remarkably, doping the synthetic polymer into the 3,4-dihydroxyphenylacetic acid-modified gelatin network forms a semi-interpenetrating polymer network which can effectively improve the rigidity, tissue adhesion, and antibacterial property of fabricated hydrogel adhesives. Moreover, non-covalent bonds from coordination interaction between catechol and Fe3+ contribute to the fast self-healing of the developed hydrogel adhesives. These hydrogel adhesives with the multiple merits including the degradability, enhanced tissue adhesion, superior self-healing, good cytocompatibility, and antibacterial property show the great potential to be used as tissue adhesives in biomedical fields.


Asunto(s)
Hidrogeles , Adhesivos Tisulares , Adhesivos , Antibacterianos/química , Antibacterianos/farmacología , Vendajes , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Adherencias Tisulares , Adhesivos Tisulares/farmacología
7.
AAPS PharmSciTech ; 12(4): 1136-43, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21892695

RESUMEN

The present investigation was undertaken with the objective of developing a solid formulation containing nitrendipine nanocrystals for oral delivery. Nitrendipine nanocrystals were prepared using a tandem precipitation-homogenization process. Then, spray drying, a cost-effective method very popular in industrial situations, was employed to convert the nanocrystals into a solid form. The parameters of the preparation process were investigated and optimized. The optimal process was as follows: firstly, nitrendipine/acetone solution (100 mg/ml) was added to a polyvinyl alcohol solution (1 mg/ml) at 10°C, then the pre-suspension was homogenized for 20 cycles at 1,000 bar. Both differential scanning calorimetry and X-ray diffraction analysis indicated that nitrendipine was present in crystalline form. The in vitro dissolution rate of the nanocrystals was significantly increased compared with the physical mixture and commercial tablet. The in vivo testing demonstrated that the C(max) of the nanocrystals was approximately 15-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively. In addition, the AUC(0→24) of the nanocrystals was approximately 41-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively.


Asunto(s)
Bloqueadores de los Canales de Calcio/química , Nanopartículas , Nanotecnología , Nitrendipino/química , Tecnología Farmacéutica/métodos , Acetona/química , Administración Oral , Animales , Disponibilidad Biológica , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacocinética , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Cristalografía por Rayos X , Composición de Medicamentos , Cinética , Masculino , Nitrendipino/administración & dosificación , Nitrendipino/farmacocinética , Tamaño de la Partícula , Alcohol Polivinílico/química , Ratas , Ratas Wistar , Solubilidad , Comprimidos
8.
Ann Transl Med ; 9(12): 963, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34277763

RESUMEN

BACKGROUND: Sagliker syndrome (SS) is characterized by a severe uglifying facial appearance resulting from untreated or inadequately treated secondary hyperparathyroidism (SHPT). To date, the craniofacial morphology of patients with SS has yet to be analyzed. The present research sought to cephalometrically evaluate the craniofacial features of patients with SS and to perform an in-depth analysis of their serum biochemical parameters, with the aim of furthering the theoretical basis for the early diagnosis and prevention of SS. METHODS: A retrospective chart review of 9 patients who fulfilled the diagnostic criteria for SS were included in this study, and their serum biochemical parameters were collected. After subjecting standard lateral cephalometric radiographic images to correction for distortions caused by magnification followed by digitization, we conducted a cephalometric analysis. Student's two-tailed t tests or Mann-Whitney U tests were used to analyze the data. Thirty-three patients with patients with SHPT alone were also included as controls. RESULTS: The lower anterior facial height (ANS-ME) and total anterior facial height (N-Me) measurements of patients with SS were significantly increased compared to those of the controls. The angles between the Frankfort horizontal, palatal, and occlusal planes and the mandibular plane, were greater in the SS group than in the control group, as was the gonial angle. Patients with SS also exhibited a significantly larger maxillary protrusion angle and relative position of the maxilla to the mandible. Most patients with SS had class II malocclusion, whereas most of the controls exhibited normal occlusion. Soft tissue largely followed the same pattern as craniofacial changes. Our investigation also showed that among patients with SHPT, female sex, longer duration of dialysis, and higher serum levels of alkaline phosphatase and intact parathyroid hormone were associated with development to SS. CONCLUSIONS: Patients with SS show facial and biochemical differences compared to patients with SHPT. Female sex, long dialysis duration, and high serum levels of intact parathyroid hormone and alkaline phosphatase may be potential risk factors for SS.

9.
Biosensors (Basel) ; 11(10)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34677319

RESUMEN

Infections of orchids by the Odontoglossum ringspot virus or Cymbidium mosaic virus cause orchid disfiguration and are a substantial source of economic loss for orchid farms. Although immunoassays can identify these infections, immunoassays are expensive, time consuming, and labor consuming and limited to sampling-based testing methods. This study proposes a noncontact inspection platform that uses a spectrometer and Android smartphone. When orchid leaves are illuminated with a handheld optical probe, the Android app based on the Internet of Things and artificial intelligence can display the measured florescence spectrum and determine the infection status within 3 s by using an algorithm hosted on a remote server. The algorithm was trained on optical data and the results of polymerase chain reaction assays. The testing accuracy of the algorithm was 89%. The area under the receiver operating characteristic curve was 91%; thus, the platform with the algorithm was accurate and convenient for infection screening in orchids.


Asunto(s)
Orchidaceae , Teléfono Inteligente , Inteligencia Artificial , Enfermedades de las Plantas/virología , Reacción en Cadena de la Polimerasa , Potexvirus , Tobamovirus
10.
Pharm Dev Technol ; 15(6): 644-52, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19943738

RESUMEN

The key structural requirement for the antitumor activity of 10-hydroxycamptothecin (HCPT) is the intact lactone moiety which is always instability and suffered from pH-dependent hydrolysis. The aim of this study was to evaluate the protection effects of liposomal encapsulation on the labile lactone ring. Mono-modal dispersed quasi-spherical liposomes with mean diameter of 145 nm and high drug entrapment efficiency of 90% were obtained under optimal conditions. The in vitro hydrolysis kinetics behaviors of lactone were studied in varied pH buffers. Compared to that of free HCPT in solution formulation, both the hydrolysis half-life and observed equilibrium constant of liposomal HCPT were increased significantly along with the decreased apparent hydrolysis rate constant. The plasma pharmacokinetics was studied by assessing the lactone stability versus time profiles in vivo following intravenous administration of free and liposomal HCPT. The liposomal encapsulation led to a twofold increase in the AUC values and significant decrease in the plasma clearance of lactone (P < 0.05). There was a good correlation between in vitro and in vivo stability of HCPT-lactone. These results suggested a potential application of the novel liposome formulation for the stable delivery system of HCPT.


Asunto(s)
Antineoplásicos Fitogénicos/farmacocinética , Camptotecina/análogos & derivados , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Área Bajo la Curva , Camptotecina/administración & dosificación , Camptotecina/química , Camptotecina/farmacocinética , Estabilidad de Medicamentos , Semivida , Concentración de Iones de Hidrógeno , Hidrólisis , Liposomas , Conejos , Factores de Tiempo
11.
Int J Nanomedicine ; 15: 7297-7314, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33061382

RESUMEN

BACKGROUND: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight. METHODS: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The transfection efficiency of dPSP nanoparticle was evaluated in vitro. RESULTS: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA/dPSP nanoparticle increased significantly. CONCLUSION: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polyspermine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.


Asunto(s)
Expresión Génica/efectos de los fármacos , Técnicas de Transferencia de Gen , Nanopartículas/química , Polímeros/química , Animales , Reactivos de Enlaces Cruzados/química , Glutatión/química , Hemólisis/efectos de los fármacos , Peróxido de Hidrógeno/química , Verde de Indocianina/química , Rayos Infrarrojos , Ratones , Peso Molecular , Células 3T3 NIH , Nanopartículas/uso terapéutico , Oxidación-Reducción , Tamaño de la Partícula , Fototerapia/métodos , Plásmidos , Polímeros/síntesis química , Oxígeno Singlete/química , Espectroscopía Infrarroja por Transformada de Fourier , Espermina/química , Transfección
12.
Drug Dev Ind Pharm ; 35(2): 177-84, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19016099

RESUMEN

A novel poly(lactic acid-co-glycolic acid) nanoparticle loaded with insulin-lauryl sulfate complex was prepared by spontaneous emulsion solvent diffusion method. The effects of key parameters such as agitation speed, poly(vinyl alcohol) concentration, solvent composition, polymer concentration, and the volume of external aqueous phase on the properties of the nanoparticles were investigated. To enhance the drug recovery and drug content simultaneously, a response surface methodology with five-level, two-factor central composite design was employed. The weight ratio of polymer to drug and volume ratio of external aqueous phase to solvent phase were selected as controlled factors on account of their interactions found in the monofactorial investigations. The experimental datum allowed the development of quadratic models (p < .05) describing the inter-relationships between the dependent and independent variables. By solving the regression equation, and graphic analyzing the response surface contour and plots, the optimum values of the two factors were determined as 20/1 and 10/1. The optimized conditions led to 89.6% of drug recovery and 4.57% of drug content during nanoparticle preparation.


Asunto(s)
Sistemas de Liberación de Medicamentos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Ácido Láctico/química , Ácido Poliglicólico/química , Dodecil Sulfato de Sodio/química , Tensoactivos/química , Difusión , Emulsiones , Hipoglucemiantes/química , Insulina/química , Nanopartículas/química , Nanotecnología/métodos , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Alcohol Polivinílico/química , Análisis de Regresión , Solventes/química
13.
Drug Dev Ind Pharm ; 35(8): 959-68, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19274512

RESUMEN

The water-soluble peptide, melittin, was modified with an anionic agent, sodium dodecyl sulfate by hydrophobic ion-pairing. Investigations showed that the formed complex was very soluble in organic solvent, especially, in dimethylsulfoxide and dehydrated alcohol. Furthermore, the physiochemical properties of the complex in the solid state or in an aqueous medium were characterized using octanol/water partition measurement, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The complex was formulated into poly(D,L-lactide-co-glycolide acid) nanoparticles by an emulsion solvent diffusion method. It was found that the nanoparticles of about 130 nm in size can be produced with a high encapsulation efficiency, and the entrapment of nanoparticles prepared with the formed complex increased from about 50% to nearly 100% compared with that for pure melittin. Moreover, the growth inhibitory effects of modified melittin and melittin-loaded nanoparticles in breast cancer MCF-7 cells were not changed comparing with free melittin as determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay.


Asunto(s)
Ácido Láctico/química , Meliteno/administración & dosificación , Ácido Poliglicólico/química , Dodecil Sulfato de Sodio/química , Tensoactivos/química , Neoplasias de la Mama/metabolismo , Rastreo Diferencial de Calorimetría , Línea Celular Tumoral , Química Farmacéutica/métodos , Dimetilsulfóxido/química , Portadores de Fármacos/química , Femenino , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solubilidad , Solventes/química , Espectroscopía Infrarroja por Transformada de Fourier
14.
J Pharm Sci ; 108(9): 2994-3002, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31047941

RESUMEN

Gastrointestinal responsive polymeric nanospheres (NPs) based on hydroxypropyl methylcellulose phthalate were prepared using spontaneous emulsification solvent diffusion method for improved oral administration of insulin. The NPs prepared under optimized conditions have an encapsulation efficiency of 90% and a particle size of about 200 nm. In vitro drug release experiments demonstrated that the NPs exhibited a gradient release profile of loaded drug when the pH value gradually increased from 3.0 to 7.4. Enzyme resistance experiments showed that under simulated gastrointestinal conditions, the NPs protected more than 60% of the drug from being degraded by trypsin. The oral hypoglycemic experiments revealed that insulin-loaded NPs could significantly reduce blood glucose levels in diabetic rats with a relative bioavailability of 8.6%. Ex vivo imaging investigation of rat tissues showed that the drug-loaded NPs could promote the absorption of insulin in the ileum and colon. The work described here suggests that the gastrointestinal responsive polymeric NPs may be promising candidates for improving gastrointestinal tract delivery of hydrophilic biomacromolecules. Accordingly, the results indicated that hydroxypropyl methylcellulose phthalate NPs with gastrointestinal stimuli responsiveness could be a promising candidate for oral insulin delivery.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Portadores de Fármacos/química , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Nanosferas/química , Administración Oral , Animales , Disponibilidad Biológica , Glucemia/análisis , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Tracto Gastrointestinal/química , Tracto Gastrointestinal/metabolismo , Concentración de Iones de Hidrógeno , Hipoglucemiantes/farmacocinética , Insulina/farmacocinética , Absorción Intestinal , Mucosa Intestinal/metabolismo , Masculino , Metilcelulosa/análogos & derivados , Metilcelulosa/química , Polímeros/química , Ratas , Estreptozocina/toxicidad
15.
Oral Oncol ; 44(5): 477-83, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-17936673

RESUMEN

Early diagnosis of oral squamous cell carcinoma (OSCC) and precursor lesions is an attractive strategy to decrease patient morbidity and mortality, but presently there are no satisfied diagnostic approaches. This study proposed a metabonomics-based diagnostic approach for OSCC and its precancerous lesions, including oral lichen planus (OLP) and oral leukoplakia (OLK). Saliva samples were collected from patients and healthy donors, and HPLC/MS analysis was performed to acquire metabolic profiles. Diagnostic model was then constructed with hierarchical principal component analysis (HPCA) and discriminate analysis algorithms. The results indicate that metabolic profiling can properly describe the pathologic characteristics of OSCC, OLP and OLK. HPCA combined with kernel fisher discriminant analysis achieved 100% accuracy in diagnosis of test samples, which is superior to direct principal component analysis and other modeling algorithms. The metabonomic approach based on the integral investigation of oral metabolites enables the detection of OSCC and precancerous lesions on noninvasive saliva samples. The proposed approach is noninvasive, efficient and low-cost, and it can be developed as a promising method for population-based screening of cancers and precancers in the oral cavity.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Leucoplasia Bucal/diagnóstico , Liquen Plano Oral/diagnóstico , Metabolómica/métodos , Neoplasias de la Boca/diagnóstico , Adulto , Algoritmos , Carcinoma de Células Escamosas/metabolismo , Diagnóstico Precoz , Femenino , Humanos , Leucoplasia Bucal/metabolismo , Liquen Plano Oral/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Masculino , Neoplasias de la Boca/metabolismo , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/metabolismo , Saliva/química
16.
Drug Des Devel Ther ; 12: 1-8, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29296076

RESUMEN

The aim of this study was to develop PEGylation liposomes formulations of erlotinib and evaluate their characteristics, stability, and release characteristics. The average particle sizes and entrapment efficiency of PEGylation erlotinib liposomes are 102.4±3.1 nm and 85.3%±1.8%, respectively. Transmission electron microscopy images showed that the liposomes dispersed well with a uniform shape and no changes during the storage. The in vitro drug-release kinetic model of erlotinib release from the PEGylation liposomes in phosphate-buffered saline fit well with the Higuchi equation. In vitro anticancer activity assay showed that the blank liposomes had lower cellular cytotoxicity and that the cellular cytotoxicity of erlotinib liposomes increased significantly under the same incubation condition, which should contribute to the increase in intracellular drug concentration by the transportation of liposomes. The two liposomes of erlotinib (with and without PEGylation) exhibited similar cellular cytotoxicity with no significantly different concentrations. Pharmacokinetic results indicated that erlotinib-loaded PEGylation liposomes can significantly change the pharmacokinetic behavior of drugs and improve the drug bioavailability by nearly 2 times compared to ordinary liposomes. No sign of damages such as the appearance of epithelial necrosis or sloughing of epithelial cells was detected in histological studies.


Asunto(s)
Antineoplásicos/administración & dosificación , Clorhidrato de Erlotinib/administración & dosificación , Lípidos/química , Neoplasias Pulmonares/tratamiento farmacológico , Nanomedicina/métodos , Nanopartículas , Inhibidores de Proteínas Quinasas/administración & dosificación , Tecnología Farmacéutica/métodos , Células A549 , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidad Biológica , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Clorhidrato de Erlotinib/química , Clorhidrato de Erlotinib/farmacocinética , Humanos , Inyecciones Intravenosas , Liposomas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Tamaño de la Partícula , Polietilenglicoles/química , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacocinética , Ratas Sprague-Dawley , Solubilidad , Ensayos Antitumor por Modelo de Xenoinjerto
17.
ACS Appl Mater Interfaces ; 10(38): 32747-32759, 2018 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-30157634

RESUMEN

Poly( N-isopropylacrylamide) (PNIPAAm), a typical thermoresponsive polymer, exhibits potential application in smart materials. However, bulk PNIPAAm hydrogel monoliths undergo slow volume phase transition at least tens of minutes to hours as determined by the shape and size of polymers due to the formation of the skin layer. In this regard, novel macroporous sponges with rapid thermoresponse are prepared via grafting polymerization of N-isopropylacrylamide (NIPAAm) onto the macroporous poly(vinyl alcohol) formaldehyde (PVF) network as confirmed by attenuated total reflection-infrared (ATR IR) and 1H NMR spectra. As prepared PVF- g-PNIPAAm sponges display interconnected open-cell structures, and their average pore sizes and porosities are ∼90 µm and >85%, respectively. The equilibrium swelling ratio of PVF- g-PNIPAAm sponges varies from 11 to 50 with temperature. The volume phase transition temperature is at 30-34 °C, as detected in the DSC curves of swollen samples. These features indicate that the existence of the original PVF network exerts almost no influence on the PNIPAAm temperature responsibility. As prepared samples can reach the swelling equilibrium in less than 80 s, and their rapid swelling kinetics can be fitted using the pseudo-first-order rate kinetic equation. Notably, the samples also display rapid deswelling rate in less than 40 s at relative high temperature (48 °C), thereby indicating a superfast responsive behavior to temperature change. The PVF- g-PNIPAAm sponges exhibit rapid and reversible thermoresponse in repeatable swelling-deswelling cycles, which can satisfy the need of special smart materials. In particular, combined with iodine solution (i.e., PVF- g-PNIPAAm/I2), these sponges can serve as a novel temperature indicator and exhibit excellent antibacterial performances.


Asunto(s)
Acrilamidas/química , Materiales Biocompatibles/química , Formaldehído/química , Hidrogeles/química , Temperatura , Polímeros/química , Alcohol Polivinílico/química
18.
Onco Targets Ther ; 11: 8555-8564, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30584316

RESUMEN

OBJECTIVE: CAM2028 (Episil®; Camurus AB, Lund, Sweden) is a liquid for use in the oral cavity to treat various pains associated with mouth injuries. Upon contact with the swollen oral mucosa, the oral liquid forms a thin protective film that acts as a mechanical barrier to relieve pain. This study was the first in China to evaluate the local analgesic effect of oral liquid in cancer patients who developed oral mucositis following chemotherapy and/or radiotherapy. METHODS: A total of 60 patients were randomized in a 1:1 ratio to the CAM2028 group (the pump device was firmly pressed three times and the fluid was distributed to the painful area of the oral cavity) or KS (a mucoadhesive oral wound rinse, Kangsu™; Luye Pharmaceutical Co. Ltd, Nanjing, China) group (5 mL of the oral rinse was poured into and kept in the oral cavity for at least 1 minute). The primary endpoint was the area under the oral mucosal pain score-time curve (AUC) within 6 hours of treatment in the trial and control groups. Medical device adverse events were assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Statistical analyses were performed using the chi-squared test (Fisher's exact test), independent-samples t-test, and analysis of covariance. RESULTS: Sixty patients were included in the per-protocol set population analysis. The average (mean ± SD) 6-hour AUC of the CAM2028 group and the KS group was 14.20±10.29 and 24.46±14.15, respectively. The difference between the groups was statistically significant (P=0.0022). The incidence of adverse events in the trial group and the control group was 16.67% and 30.0%, respectively, and there was no statistical difference. CONCLUSIONS: CAM2028 displayed an efficacious local analgesic effect in cancer patients who developed oral mucositis following chemotherapy and/or radiotherapy. The results demonstrated its potential value in clinical applications.

19.
J Pharm Sci ; 96(2): 421-7, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17051590

RESUMEN

The aim of the present work was to investigate the preparation of PLGA nanoparticles (PNP) and PLGA-Hp55 nanoparticles (PHNP) as potential drug carriers for oral insulin delivery. The nanoparticles were prepared by a modified emulsion solvent diffusion method in water, and their physicochemical characteristics, drug release in vitro and hypoglycemic effects in diabetic rats were evaluated. The particle sizes of the PNP and PHNP were 150+/-17 and 169+/-16 nm, respectively, and the drug recoveries of the nanoparticles were 50.30+/-3.1 and 65.41+/-2.3%, respectively. The initial release of insulin from the nanoparticles in simulated gastric fluid over 1 h was 50.46+/-6.31 and 19.77+/-3.15%, respectively. The relative bioavailability of PNP and PHNP compared with subcutaneous (s.c.) injection (1 IU/kg) in diabetic rats was 3.68+/-0.29 and 6.27+/-0.42%, respectively. The results show that the use of insulin-loaded PHNP is an effective method of reducing serum glucose levels.


Asunto(s)
Hipoglucemiantes/química , Insulina/química , Ácido Láctico/química , Metilcelulosa/análogos & derivados , Nanopartículas , Ácido Poliglicólico/química , Polímeros/química , Administración Oral , Animales , Glucemia/análisis , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Jugo Gástrico/metabolismo , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , Insulina/farmacocinética , Insulina/farmacología , Secreciones Intestinales/metabolismo , Masculino , Metilcelulosa/química , Microscopía Electrónica de Rastreo , Nanopartículas/ultraestructura , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Ratas Wistar
20.
Drug Deliv ; 24(sup1): 22-32, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29069920

RESUMEN

To prolong the circulation time of drug, PEGylation has been widely used via the enhanced permeability and retention (EPR) effect, thereby providing new hope for better treatment. However, PEGylation also brings the "PEG dilemma", which is difficult for the cellular absorption of drugs and subsequent endosomal escape. As a result, the activity of drugs is inevitably lost after PEG modification. To achieve successful drug delivery for effective treatment, the crucial issue associated with the use of PEG-lipids, that is, "PEG dilemma" must be addressed. In this paper, we introduced the development and application of nanocarriers with cleavable PEGylation, and discussed various strategies for overcoming the PEG dilemma. Compared to the traditional ones, the vehicle systems with different environmental-sensitive PEG-lipids were discussed, which cleavage can be achieved in response to the intracellular as well as the tumor microenvironment. This smart cleavable PEGylation provides us an efficient strategy to overcome "PEG dilemma", thereby may be a good candidate for the cancer treatment in future.


Asunto(s)
Polietilenglicoles/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Humanos , Lípidos/química , Nanopartículas/química , Permeabilidad , Microambiente Tumoral/efectos de los fármacos
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