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1.
《Pharmaceutical development and technology》2013,18(1):36-43
Potent immunoadjuvants are needed to elicit responses following mucosal delivery. PLGA (poly[D,L-lactic-co-glycolic acid]) nanospheres, Quillaja saponin (QS) and cross-linked dextran microspheres (CDM) as drug delivery and absorption enhancer adjuvants were evaluated. PLGA nanospheres were prepared by solvent evaporation method. Particulate characteristics of nanospheres were studied by optical and scanning electron microscopes and dynamic light scattering technique. The mean diameter of nanospheres encapsulated with TT and TT?+?QS determined as 425 and 390?nm. Loadings of TT and QS were 30?±?1.9% and 23?±?2.8%. Nanospheres encapsulated with TT or QS were intranasally administered to rabbits, three times in two-week intervals and the serum IgG and nasal lavage IgA titers were determined by ELISA. The serum IgG titer induced with (TT)PLGA nanospheres was higher than TT solution (P?<?0.001). IgG titers induced with (TT?+?QS)PLGA was higher than (TT)PLGA (P?<?0.0001). When (TT)PLGA and (TT?+?QS)PLGA nanospheres were mixed with CDM, higher IgG titers were induced (P?<?0.001). The highest mucosal sIgA titers were seen in animals immunized with (TT?+?QS)PLGA?+?CDM. Co-encapsulation of QS and TT in PLGA nanospheres increased sIgA titers. In conclusion, the highest immune responses were observed by concomitant use of three adjuvants. 相似文献
2.
Sajadi Tabassi SA Tafaghodi M Jaafari MR 《International journal of pharmaceutics》2008,360(1-2):12-17
Poor absorption of protein antigens through the mucosal membranes necessitates the use of mucoadhesive delivery systems. Regarding the advantages of mucosal immunization and also the penetration enhancement potential of dextran microspheres, in this study the adjuvant potential of these microspheres was compared with CpG-ODN. Cross-linked dextran microspheres (CDMs) were loaded with tetanus toxoid (TT). In vitro release studies were performed in a model, simulating the nasal cavity. The immunoreactivity of encapsulated TT was assayed by ELISA. Membrane toxicity and local irritating potential of CDM was examined by erythrocyte hemolysis and nasal administration to human nose, respectively. The various formulations were nasally administered to rabbits (n=4). Alum-adsorbed TT (AATT) was injected as the positive control. The serum IgG and nasal lavage sIgA titers were determined by ELISA method. Serum antitoxin titers were determined by toxin neutralization (TN) bioassay method. Mean diameter of CDM was 128.1+/-25.8 microm. Mean encapsulation efficiency was 20.3+/-3.2% (n=3). Antigenicity of encapsulated TT was 90.5+/-1.8% (n=3) that of original TT. Hemolysis studies showed no membrane disruption by CDM and none of the human subjects reported nasal irritation. Among the nasally immunized animals, the highest antitoxin titers was seen in the group immunized with CDM+TT (P<0.0001). The serum IgG titers of the CDM+TT group was higher than the TT solution group (P<0.05). The adjuvant potentials of CDM and CpG-ODN in inducing IgG titers was not significantly different (P>0.05). The lowest sIgA titers in the bronchial lavage were seen in the group of animals received AATT parenterally. Considering the proper release characteristics, desirable preservation of the antigen activity of TT, good mucoadhesion properties and also safety of CDM+TT, these microspheres could be regarded as an efficient mucosal adjuvant and antigen delivery system. These microspheres could induce very high antitoxin titers following nasal administration, while the CpG-ODN could not induce such titers. The antitoxin titers induced by CDM+TT was 175 times higher than the protective levels. 相似文献
3.
Mohsen Tafaghodi Mahmood-Reza Jaafari Sayyed Abolghasem Sajadi Tabassi 《European journal of pharmaceutics and biopharmaceutics》2006,64(2):138-145
To increase the systemic and mucosal immune responses against the nasally administered tetanus toxoid, liposomes as a drug delivery system and CpG-ODN as an adjuvant were evaluated. Rabbits were nasally immunized with entrapped tetanus toxoid (TT) and CpG-ODN in neutral liposomes and systemic and mucosal immune responses were determined. Liposomes containing TT and CpG-ODN were prepared by dehydration-rehydration method. The volume mean diameter of liposomes was 2.3+/-0.6 microm. Encapsulation efficiency of TT and CpG-ODN was determined as 54.0+/-8.8 and 60.1+/-7.4, respectively. The leakage of the encapsulated TT from liposomes reached 7.38% after 3 months. Encapsulated TT kept its intact structure, and its immunoreactivity was also completely preserved, as shown by SDS-PAGE and ELISA methods. The highest serum IgG and antitoxin titers were observed in groups immunized with solution formulations (P < 0.001). However the highest mucosal sIgA titers were achieved by liposomes encapsulated with TT. CpG-ODN as an adjuvant was able to increase the serum IgG and antitoxin titers when co-administered with TT solution (P < 0.05) or co-encapsulated with TT in liposomes (P < 0.01), but failed to increase the sIgA titers in nasal lavages. No hemolysis occurred on incubation of liposomes and human RBCs. Also after nasal administration of plain liposomes to human volunteers, no local irritation was seen. Intranasal administration of liposomes encapsulated with vaccines showed to be an effective way for inducing the mucosal immune responses. 相似文献
4.
《Pharmaceutical development and technology》2013,18(5):571-576
AbstractThis study aimed at improving the oral bioavailability of acyclovir (ACV) through incorporating it into gastroretentive dosage form based on floating hollow chitosan beads. Hollow chitosan beads were prepared using a solvent free, ionotropic gelation method. The effect of formulation parameters, including chitosan molecular weight and drug concentration, on bead characteristics was studied. The drug containing formulations had yields >70.5?±?0.31%. The entrapment efficiencies for the medium molecular weight chitosan formulations (56.29?±?0.94%–62.75?±?0.86%) was greater than the high molecular weight chitosan formulation (29.21?±?0.89%). The density of all formulations was below that of gastric fluid, the greatest density observed was 0.60?±?0.01?g?cm?3. Unsurprisingly, the formulations were immediate bouyant to different degrees in both pH 1.2 and pH 6.8 media. In addition, the chitosan beads were all seen to swell in pH 1.2 media and demonstrated mucoadhesive properties. A sustained release profile was observed from the chitosan beads, the developed formulations released drug at slower rates than a marketed ACV oral tablet. The developed system has the dual advantages of being gastroretentive, to increase oral bioavailability and releasing drug in a controlled manner, to reduce the required frequency of administration thereby promoting patient adherence. 相似文献
5.
Zeynep Duru 《Cutaneous and ocular toxicology》2019,38(2):190-195
Purpose: Islamic Ramadan is the month of fasting, in which intake of food and drink is restricted from sunrise until sunset. The objective of the present study was to find out the effects of religious fasting on posterior ocular structures.Materials and methods: In this prospective study, 34 eyes of 34 healthy volunteers with a mean age of 34.09?±?7.20?years were enrolled. Volunteers with any systemic disorder and eyes with pathology or previous surgery were excluded. One week before Ramadan (non-fasting period) and during Ramadan (fasting period) at the same hours (at 08:00 and 16:00?h), choroidal, macular, and retinal nerve fibre layer (RNFL) thicknesses were measured by spectral domain optical coherence tomography. Results were compared using paired sample t-test, and a p value <0.05 was accepted as statistically significant.Results: The comparison of 16:00-h measurements significantly revealed lower values during fasting period when compared non-fasting period for choroidal thickness (non-fasting and fasting, respectively; subfoveal: 299.26?±?41.3 and 280.03?±?38.75 p?0.001, nasal: 246.09?±?53.59 and 227.06?±?53.82 p?0.001, and temporal: 273.56?±?42.68 and 257.44?±?45.06 p?=?0.001) and paracentral macular thickness (superior: p?=?0.002, inferior: p?=?0.010, temporal: p?=?0.013, and nasal: p?=?0.016). By contrast, no significant differences were found in the central macular thickness between the fasting and non-fasting periods (p?=?0.735). Also, no statistically significant difference was noted for RNFL thickness at the different periods and time points.Conclusion: Our results reveal that Islamic religious fasting is associated with statistically significant alterations in choroidal and paracentral macular thickness in healthy volunteers. However, more detailed investigations should be designed to evaluate whether fasting has a pivotal influence on pathological conditions. 相似文献
6.
《Expert opinion on drug delivery》2013,10(6):827-842
Objective: The present work evaluated whether the prepared nanoparticles (NPs) would be able to target the drug to the brain by a non-invasive nasal route enhancing its bioavailability. Methods: Bromocriptine (BRC) chitosan NPs (CS NPs) were prepared by ionic gelation method. The biodistribution, pharmacokinetic parameters and dopamine concentration was analysed by ultra-HPLC/mass spectrometry method. The histopathological examination in haloperidol-induced Parkinson's disease in mice model following intranasal (i.n.) administration was evaluated. Results: BRC was found stable in all exposed conditions and the percentage accuracy observed for intra-day and inter-day batch samples ranged from 90.5 to 107% and 95.3 to 98.9% for plasma and brain homogenates, respectively. BRC-loaded CS NPs showed greater retention into the nostrils (42 ± 8.5% radioactivity) for about 4 h, whereas the 44 ± 7.5% could be retained up to 1 h for BRC solution. The brain:blood ratios of 0.96 ± 0.05 > 0.73 ± 0.15 > 0.25 ± 0.05 of BRC-loaded CS NPs (i.n.) > BRC solution (i.n.) > BRC-loaded CS NPs (intravenous), respectively, at 0.5 h indicated direct nose-to-brain transport bypassing blood–brain barrier. BRC-loaded CS NPs administered intranasally showed significantly high dopamine concentration (20.65 ± 1.08 ng/ml) as compared to haloperidol-treated mice (10.94 ± 2.16 ng/ml) (p < 0.05). Histopathology of brain sections showed selective degeneration of the dopaminergic neurons in haloperidol-treated mice which was markedly reverted by BRC-loaded CS NPs. Conclusion: Nanoparticulate drug delivery system could be potentially used as a nose-to-brain drug delivery carrier for the treatment of Parkinson's disease. 相似文献
7.
Jaleh Varshosaz Mohsen Minaiyan Mohammad Reza Zaki Milad Fathi Hossein Jaleh 《Drug delivery》2016,23(6):1948-1954
AbstractBupropion HCl is an atypical antidepressant drug with rapid and high first-pass metabolism. Sustained release dosage form of this drug is suggested for reducing its side effects which are mainly seizures. The aim of the present study was to design pulmonary agar nanospheres of bupropion HCl with effective systemic absorption and extended release properties. Bupropion HCl was encapsulated in agar nanospheres by ionic gelation, and characterized for physical and release properties. Pharmacokinetic studies on nanospheres were performed on rats by intratracheal spraying of 5?mg/kg of drug in form of nanospheres compared to intravenous and pulmonary delivery of the same dose as simple solution of the drug. The optimized nanoparticles showed particle size of 320?±?90?nm with polydispersity index of 0.85, the zeta potential of ?29.6?mV, drug loading efficiency of 43.1?±?0.28% and release efficiency of 66.7?±?2%. The area under the serum concentration–time profile for the pulmonary nanospheres versus simple solution was 10?237.84 versus 28.8?µg/ml?min, Tmax of 360 versus 60?min and the Cmax of 1927.93 versus9.93?ng/ml, respectively. The absolute bioavailability of the drug was 86.69% for nanospheres and 0.25% for pulmonary simple solution. Our results indicate that pulmonary delivery of bupropion loaded agar nanospheres achieves systemic exposure and extends serum levels of the drug. 相似文献
8.
《Journal of microencapsulation》2013,30(8):807-815
In this study, the potential of lecithin/chitosan nanoparticles (NPs) as colloidal nanosystem for transdermal melatonin delivery was investigated. Mean diameter and zeta-potential of NPs differing in lecithin type (Lipoid S45 and S100) and chitosan content ranged between 113.7 and 331.5?nm and 4.6 and 31.2?mV, respectively. Melatonin loadings were up to 7.2%. The potential of lecithin/chitosan NPs to enhance transdermal melatonin delivery was investigated by determining the drug flux across dermatomed porcine skin and its skin deposition. Lecithin/chitosan NPs provided 1.3–2.3-fold higher flux compared to melatonin solution. The highest flux, 9.0?±?0.21?µg/cm2/h, was observed for S45 lecithin/chitosan NPs with lecithin/chitosan weight ratio of 20:1. NP possible cytotoxicity in vitro was evaluated using human skin keratinocytes and fibroblasts. It was demonstrated that lecithin/chitosan NPs can be applied to skin cells at concentrations up to 200?µg/mL without inducing plasma membrane damage or cell viability decrease. 相似文献
9.
Karen O. Klein Ahmed M. Soliman ElizaBeth Grubb Paul Nisbet 《Current medical research and opinion》2020,36(3):411-418
AbstractObjective: To describe the timeline to diagnosis for children with central precocious puberty (CPP) and evaluate their psychosocial and health-related quality of life (HRQoL).Methods: A cross-sectional survey was used to prospectively collect data from caregivers, recruited via the MAGIC Foundation, of children with CPP. The control (non-CPP) group was recruited from a national panel of parents/caregivers. After completing a screening survey, respondents completed a burden of illness survey. Respondents in both groups completed the Pediatric Quality of Life Inventory (PedsQL) and Patient-Reported Outcomes Measurement Information System (PROMIS) peer relationship instruments.Results: Responses from 142 caregivers of children with and 300 without CPP were assessed. Mean time to treatment after a child’s visit to the pediatric endocrinologist was 220?days and time from onset of symptoms to initiating treatment was approximately 2?years. Responses to HRQoL inventories were all lower in children with CPP versus non-CPP. Adjusted mean (± standard error) PedsQL total (65.3?±?1.8 versus 75.7?±?1.2), Psychosocial Health Summary (62.4?±?1.8 versus 73.4?±?1.2), and Physical Health Summary (70.7?±?2.2 versus 79.9?±?1.5) scores were significantly lower (p?<?.01) in CPP versus non-CPP group. PROMIS peer relationship T score (± standard error) was numerically lower for the CPP versus non-CPP group (45.4?±?1.0 versus 47.4?±?0.7, p = .11).Conclusions: In clinical practice, there is a longer than expected delay between CPP symptom onset and referral to an endocrinologist and ultimate treatment. Children with CPP experience a substantial disease burden with a significant impact on emotional, social, and physical functioning compared with children without CPP. 相似文献
10.
Hamed Nosrati Marziyeh Salehiabar Zahra Bagheri Hamid Rashidzadeh Soodabeh Davaran 《Pharmaceutical development and technology》2018,23(10):1156-1167
AbstractThis study is a report about the synthesis iron oxide magnetic nanoparticles (IONPs) which modified with positive and negative charged amino acids (AAs). l-Arginine (Arg) and l-aspartic acid (Asp) which have of guanidinium and carboxylic acid groups, respectively, were selected for this study. After loading chrysin in amino acids modified iron oxide magnetic nanoparticles (F@AAs@Chrysin NPs), it was characterized by XRD, TGA, FTIR, VSM, and TEM techniques. Finally, MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AA coated IONPs. The results show that, the ζ-potential and average size of F@Arg@chrysin NPs and F@Asp@chrysin NPs were to ?3.87, ?2.12?mV, 18.75?±?2.40 (mean?±?SD (n?=?50)) nm, and 19.86?±?2.22 (mean?±?SD (n?=?48)) nm, respectively. Also, the results indicated that these F@AAs@Chrysin NPs were appropriate for delivery of chrysin. Furthermore, the phantom MRI studies showed the IONPs can be used as contrast agent for the revealing of tumor. 相似文献
11.
Context: The effects of icariin, a chief constituent of ?avonoids from Epimedium brevicornum Maxim (Berberidaceae), on the levels of HIF-1α, HSP-60 and HSP-70 remain unknown.Objective: To explore the effects of icariin on the levels of HSP-60, HIF-1α and HSP-70 neuron-specific enolase (NSE) and cell viability.Materials and methods: PC12 cells were treated with icariin (10?7, 10?6 or 10?5?mol/L) for 3?h (1?h before oxygen–glucose deprivation (OGD) plus 2?h OGD). HSP-60, HIF-1α, HSP-70 and NSE were measured using enzyme-linked immunosorbent assay (ELISA). Cell viability was determined by metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Results: After 2?h OGD, levels of HIF-1α, HSP-60, HSP-70 and NSE were increased significantly (HIF-1α: 33.3?±?1.9?ng/L, HSP-60: 199?±?16?ng/L, HSP-70: 195?±?17?ng/L, NSE: 1487?±?125?ng/L), and cell viability was significantly decreased (0.26?±?0.03), while icariin (10?7, 10?6, or 10?5?mol/L) significantly reduced the contents of HIF-1α, HSP-60, HSP-70 and NSE (HIF-1α: 14.1?±?1.4, 22.6?±?1.8, 15.7?±?2.1, HSP-60: 100?±?12, 89?±?6, 113?±?11, HSP-70: 139?±?9, 118?±?7, 95?±?9 and NSE: 1121?±?80, 1019?±?52, 731?±?88), and improved cell viability (0.36?±?0.03, 0.38?±?0.04, 0.37?±?0.03) in OGD-treated PC12 cells.Discussion and conclusion: These results indicate that the protective mechanisms of icariin against OGD-induced injury may be related to down-regulating the expression of HIF-1α, HSP-60 and HSP-70. 相似文献
12.
Context: Chlorogenic acid (ChA) is the major compound in Shuang-Huang-Lian (SHL), which is mainly composed of ChA, baicalin, and Forsythia suspense Thunb Vahl.Objective: The effects of co-existing compounds in SHL and Lonicera japanica Thunb on the absorption of ChA was investigated.Materials and methods: According to 3?×?3 Latin-square test, ChA alone, the extracts of Lonicera japanica, or the mixture of ChA, baicalin and Forsythia suspense (ChA effective doses is 60?mg/kg) was separately given to six beagles for seven days. The oral pharmacokinetic parameters of ChA in plasma, urine and faeces were quantified by HPLC/UV and analyzed.Results: The pharmacokinetic parameters of ChA alone, the extracts of Lonicera japanica, and the mixture of ChA, baicalin, and Forsythia suspense were as followed: Cmax (2.350?±?0.483, 1.655?±?0.576, 2.332?±?0.606?μg/mL), AUC0-∞ (6.324?±?1.853, 4.216?±?1.886, 6.074?±?1.473?μg·h/mL), t1/2 (0.911?±?0.187, 1.204?±?0.309, 1.094?±?0.193?h), and Tmax (1.861?±?0.499, 1.000?±?0.459, 1.833?±?0.279?h). Accumulative fraction excretion of ChA in urine were 0.73?±?0.55, 1.25?±?1.23, 1.05?±?0.96%, while that in faeces were 0.68?±?0.94, 0.19?±?0.40, and 1.76?±?3.57%.Discussion and conclusion: Co-existing compounds in SHL have no effect on the absorption of ChA, while the concomitant compounds in Lonicera japanica could decrease that of ChA. ChA in Beagles might have high biological transformation. 相似文献
13.
Sunny O. Abarikwu Rex-Clovis Njoku Chiamaka J. Lawrence Iniobong A. Charles Jude C. Ikewuchi 《Pharmaceutical biology》2017,55(1):2161-2169
Context: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating potentials.Objective: This study was designed to evaluate the protective effects of RUT against cadmium (Cd)?+?ethanol (EtOH)-induced hepatic and renal toxicity in rats.Materials and methods: Wistar rats were treated with Cd (50?mg/kg) alone or in combination with EtOH (5?mg/kg) and RUT (25, 50 and 100?mg/kg) for 15?days. After treatment, the liver, kidney and serum were removed for biochemical assays by spectrophotometric methods.Results: Serum, hepatic and renal malondialdehyde (MDA) levels were highest in the Cd?+?EtOH group and lowest in Cd?+?EtOH animals co-treated with the highest dose of RUT (2.98?±?0.34, 10.08?±?2.32, 4.99?±?1.21 vs. 1.69?±?0.33, 6.13?±?0.28, 3.66?±?1.12?μmol MDA/mg protein, respectively). The serum level of Cd was increased in the Cd?+?EtOH treated animals compared to Cd?+?EtOH animals co-treated with 100?mg/kg RUT (2.54?±?0.08 vs. 1.28?±?0.04?ppm). Furthermore, RUT at the highest dose protected against Cd?+?EtOH-induced elevation of bilirubin and uric acid levels as well as activities of lactate dehydrogenase and γ-glutamyl transferase (62.86?±?2.74 vs. 122.52?±?6.35?µmol/L; 1.77?±?0.35 vs. 3.23?±?0.55?mmol/L; 9.56?±?1.22 vs. 16.21?±?1.64?U/L; 288.92?±?40.12 vs. 159.8?±?18.01?U/L). The histo-pathological changes in the liver and kidney were also reduced in the Cd?+?EtOH animals co-treated with RUT in a dose-dependent manner.Discussion and conclusion: RUT protected against the combined effects of Cd?+?EtOH on hepatic and renal functions and improved the antioxidant defence system in the blood. 相似文献
14.
Biodegradable intranasal nanoparticulate drug delivery system of risedronate sodium for osteoporosis
Context: Osteoporosis (OP) is the most common metabolic bone disease predominantly found in elderly people. It is associated with reduced bone mineral density, results in a higher probability of fractures, especially of the hip, vertebrae, and distal radius. Worldwide prevalence of OP is considered a serious public health concern.Objective: The purpose of the present work was to develop and evaluate polymeric nanoparticles (NPs) of risedronate sodium (RIS) for the treatment of OP using intranasal (IN) route in order to reduce peripheral toxic effects.Materials and methods: Polymeric NPs of RIS were prepared by nanoprecipitation methods. Formulations were developed and evaluated in context to in vitro drug release, ex vivo permeation, in vivo study, and biochemical studies.Results and discussions: The particles size, entrapment efficiency (EE) (%), and loading capacity (LC) (%) of optimized formulations were found to be 127.84?±?6.33?nm, 52.65?±?5.21, and 10.57?±?1.48, respectively. Release kinetics showed diffusion-controlled, Fickian release pattern. Ex vivo permeation study showed RIS from PLGA-NPs permeated significantly (p?<?0.05) through nasal mucosa. In vivo study showed a marked difference in micro-structure (trabeculae) in bone internal environment. Biochemical estimation of treated group and RIS PLGA indicated a significant recovery (p?<?0.01) as compared with the toxic group.Conclusion: Polymeric NPs of RIS were prepared successfully using biodegradable polymer (PLGA). Intranasal delivery showed a good result in in vivo study. Thus PLGA-NPs have great potential for delivering the RIS for the treatment and prevention of OP after clinical evaluation in near future. 相似文献
15.
Objective: The objective of this study was to compare the efficacy and safety of pregabalin for painful diabetic peripheral neuropathy (pDPN) in subjects with type 1 (T1DM) or 2 diabetes mellitus (T2DM).Methods: Pooled data from 10 randomized clinical trials (pregabalin-treated T1DM and T2DM subjects with pDPN) were analyzed for change from baseline (CFB) scores (pain and sleep disturbance) using mixed model repeated measures (MMRM) through Week 12 and last observation carried forward (LOCF). Adverse events (AEs) were recorded.Results: Pregabalin-treated (T1DM 156 [8.7%]; T2DM 1632 [91.3%]) and placebo subjects (T1DM 92 [9.6%]; T2DM 868 [90.4%]) had comparable baseline demographic characteristics between treatment groups within the same diabetes type. T2DM (vs. T1DM) subjects were ~10 years older. With pregabalin and placebo, respectively, mean?±?SD baseline pain (T1DM: 6.2?±?1.4 and 6.5?±?1.6; T2DM: 6.5?±?1.5 and 6.4?±?1.5) and sleep scores (T1DM: 5.2?±?2.4 and 5.2?±?2.7; T2DM: 5.3?±?2.5 and 5.1?±?2.5) were comparable. Using MMRM, mean CFB treatment differences (pregabalin minus placebo) were significantly different for pain and sleep with either diabetes types (all weeks p?<?.05). With LOCF, pregabalin’s odds ratios (ORs) of achieving 30% pain reduction were similar with T2DM (OR, 1.91, 95% CI [1.61, 2.27]) and T1DM (2.01 [1.18, 3.44]) (both p ≤ .01). Pregabalin’s ORs of 30% improvement in sleep quality were 1.81 (95% CI, 1.06, 3.09) with T1DM and 2.01 (1.69, 2.39) with T2DM (both p?<?.05). AEs were consistent with the known safety profile of pregabalin.Conclusions: Pregabalin significantly improved pain and sleep quality, without a clinically meaningful difference between diabetes types.ClinicalTrial.gov registration: NCT00156078, NCT00159679, NCT00143156, NCT00553475. 相似文献
16.
《Journal of microencapsulation》2013,30(8):769-783
AbstractHere, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239–405?nm; surface charge: +18 and +27?mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC–pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination. 相似文献
17.
Ömer Kutlu 《Cutaneous and ocular toxicology》2020,39(1):67-70
AbstractBackground: Oral isotretinoin (ISO) can effect markers of inflammation in patients with acne vulgaris. To our knowledge, there are no data on the relationship between ISO and monocyte to HDL cholesterol ratio (MHR). In this study, it is aimed to examine the effect of the ISO treatment on the MHR and other inflammatory markers in patients with acne vulgaris.Materials and methods: In this study, 89 out of 120 patients with severe/very severe acne vulgaris according to the Global Acne Grading Scale who received at least 3 months of ISO treatment were evaluated. The complete blood counts including mean levels of mean platelet volume, plateletcrit (PTC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), MHR, and serum biochemistry panel were evaluated before and after ISO treatment.Results: The mean platelet value, NLR, and PLR levels underwent a statistically significant decrease after ISO treatment (p?<?0.05) while MHR increased significantly 3 months after ISO treatment (p?=?0.017). The mean platelet value, NLR, and PLR levels were 9.56?±?1.05, 2.15?±?0.81, and 142.45?±?48.33 before treatment while were 9.32?±?1.45, 1.90?±?0.99, and 127.94?±?41.38 after treatment, respectively. On the other hand, MHR was 9.76?±?4.27 and 10.86?±?4.12 before and after treatment, respectively.Conclusions: In this study, we found that ISO may have both inflammatory and anti-inflammatory effects by using MPV, PTC, NLR, PLR, and MHR. The inflammatory effects of ISO may be associated with possible inflammatory diseases. MHR can be used as a novel marker to investigate the inflammatory effect of the ISO. 相似文献
18.
Context: Alcoholic liver fibrosis (ALF) is treatable and reversible consequence of liver disease. Intestinal microflora plays an important role in the progression of liver disease. Garlic (Allium sativum L. [Amaryllidaceae]) has been consumed as a traditional medicine to treat liver injury.Objective: To investigate the effects of garlic polysaccharide (GP) on ALF and intestinal microflora in mice.Materials and methods: KM mice were orally administered with alcohol (56%, 6?mL/kg) for 30?d to establish ALF model, and divided into four groups together with control group (water only). Hugan tablet (60?mg/kg) or GP (250 and 150?mg/kg) were given 5?h after each dose of alcohol. Biochemical markers in serum and liver homogenate were determined with kits. Alteration of intestinal microflora, and protein expressions of TGF-β1, TNF-α and decorin were detected.Results: In GP-H group, ALT and AST decreased to 18.85?±?4.71?U/L and 40.84?±?7.89?U/L. MDA, TC, TG and LDL-C decreased to 2.32?±?0.86?mmol/mg, 0.21?±?0.12?mmol/L, 0.96?±?0.31?mmol/L and 0.084?±?0.027?mmol/L. SOD, GSH-Px and GSH increased to 118.32?±?16.32?U/mg, 523.72?±?64.20?U/mg and 0.56?±?0.05?mg/g. Ratios of TGF-β1 and TNF-α decreased to 0.608?±?0.170 and 1.057?±?0.058, decorin increased to 2.182?±?0.129. Lachnospiraceae and Lactobacillus increased, Facklamia and Firmicutes decreased with GP pretreatment.Discussion and conclusions: Intestinal microflora provides novel insight into the mechanisms of GP that may be used to treat ALF and intestinal microflora dysbiosis. 相似文献
19.
《Drug delivery》2013,20(5):210-215
AbstractThe aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93?µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62?±?2.4% and 78.85?±?3.1% in 6?h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23?±?2.12% and 75.25?±?0.93% blood glucose of initial BGL were observed at 6?h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits. 相似文献
20.
Abdullah S. Shatoor Suliman Al Humayed Mahmoud A. Alkhateeb Khalid A. Shatoor Hussain Aldera Mohammed Alassiri 《Pharmaceutical biology》2019,57(1):37-47
Context: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders.Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats.Materials and methods: Wistar Male rats (180–220?g) were divided (n?=?10/group) as control fed a standard diet (STD), STD + C. aronia (200?mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20?mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8?weeks, and all other treatments were administered for 4?weeks.Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90?±?5 vs. 160?±?11.3?µm) and adventitia (54.3?±?3.8 vs. 93.6?±?9.4?µm). It also lowered protein levels of TNF-α (0.51?±?0.15 and 0.15?±?0.16 vs. 0.1?±?0.09%) and IL-6 (0.52?±?0.19 vs. 1.0?±?0.2%) in their aorta or serum (5.9?±?0.91 vs. 12.98?±?1.3?ng/mL and 78.1?±?6.7 vs. 439?±?78?pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4?±?4.0 vs. 40.7?µM) and activity of SOD (5.7?±?0.7 vs. 2.9?±?0.6?U/mg) and decreased serum levels of ox-LDL-c (566.7?±?46 vs. 1817?±?147?ng/mL). Such effects were more profound than all other treatments.Conclusions: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended. 相似文献