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Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
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Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic--glycolic)acid (PLGA) large porous microparticle (LPMP) fortreatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition.studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPsairway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations fortreatment of lung cancer.
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Background: COPD is characterized by persistent airflow limitation associated with an enhanced chronic inflammatory response to noxious particles or gases in airways and lungs. Anticholinergics are bronchodilators which lead to side-effects like dry mouth, worsening glaucoma, dry cough and blurred vision on administration. Glaucoma is frequently seen in patients with chronic bronchitis who require treatment with nebulized bronchodilator drugs. Aims and objectives: The present study was done to find out the efficacy and safety of inhaled anticholinergics on intraocular pressure (IOP) in eyes of COPD and potential glaucoma patients. Methods: Total 110 patients of suspected COPD aged between 40 to 80 years were observed in this study. The diagnosis was also confirmed by spirometry and patient condition was allocated into stages as per GOLD 2014. Level of IOP before and after inhalation of drug in both eyes of patients at 2nd hour, 8th day, 15th day, 22nd day and at 28th day was analyzed. Study group (N=70) received ipratropium 40μg eight hourly or tiotropium 18 μg once a day and formoterol 6 μg twice a day plus fluticasone 125 μg twice a day and control group (N=40) received formoterol 6 μg twice a day and fluticasone 125 μg twice a day except anticholinergics. Comparison of IOP was done by statistical analysis. Results: In the present study, patients of COPD with mean age of 59± 8.84 years were observed for IOP. In study group, mean change in IOP was more (3.3±2.3 mmHg) in stage 2 than in stage 3 (1.5±1.5 mmHg) and least in stage 4 (1.3±1.06 mmHg) (p=0.035). During distribution of angle at 28th day after inhaled anticholinergics, 4 patients with narrow angle and 3 with open angle developed IOP beyond normal range(>20mmHg), but all were normal on fundoscopic examination (ocular hypertension). At the end of 28th day, there were 4 patients with ocular symptoms in study group which disappeared after discontinuing tiotropium inhaler. Conclusion: Inhaled formetrol and fluticasone with anticholinergic drugs given by PMDI leads to ocular hypertension in COPD patients whose eyes were normal at initial clinical examination whereas formetrol and fluticasone without anticholinergics did not cause any significant change in IOP. Inhaled anticholinergics increased intraocular pressure in COPD patients.
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Background: Bronchial Asthma and COPD are among the cause of substantial morbidity and mortality, the treatment and control of which is hampered by incorrect use of inhaler. Methodology: Present study is a part of another hospital based study conducted among the patients using DPI, attending the OPD and IPD of department of TB & Chest diseases, FH Medical College Hospital. The secondary analysis was done to compare the inhaler use technique among Bronchial Asthma and COPD patients. The subjects were selected non-randomly (purposely), and observed by a single observer, while they were using the inhaler. The steps were noted at which the subjects were observed to be performing incorrectly, in a pre-tested structured format. Results: The mean age was observed to be significantly higher in COPD patients (53.5±12.0 years) as compared to that of bronchial asthma patients (46.9±17.5 years). Higher proportion of bronchial asthma patients (20%) were found to be using the inhaler correctly, as compared to COPD patients (11.8%), though it was not found to be statistically significant (p>0.05). Among the bronchial asthma patients, the most frequent mistake was made during breath holding after inhalation (68%), while among COPD patients, most crucial steps were slow exhalation i.e. step 4 and forceful inhalation through the mouth i.e. step 5 (72.9%). Conclusion: Incorrect usage of inhalers is widely prevalent among its users, which is not related to the diagnosis for which it is prescribed.
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Aim To investigate the antinociception, tolerance and withdrawal abstinence of δ/μ/κ opioid receptor triple agonist KUST201 ( DPI-125 ) in rats. Methods Male Sprague-Dawley rats were used to de-termine the time course of analgesic effects and ED50 effects of co-administration of naltrindole were assessed as well. In withdrawal experiments, KUST201 was ad-ministrated twice daily for 3 d with increasing doses each day. On the 4th day, the rats were given a single dose, challenged with naloxone 3 h later, and signs of abstinence were monitored. Results The ED50 values of KUST201 were 0. 34 mg·kg-1 in tail-pinch test and 0. 68 mg · kg-1 in hot-plate test. The antinociception actions of KUST201 started to decrease 1 h after ad-ministration, and disappeared after 2 h. In chronic tol-erance experiments, the antinociception actions started to decrease on d 3 , and completely disappeared on d 7 . Naltrindole could reduce the antinociceptive action of KUST201. In withdrawal experiments, abstinence scores increased significantly in the dose range between 2~8 times of tail-pinch ED50 . Conclusion Compared with previously reported δ/μ/κ triple agonist DPI-3290 , KUST201 exhibits similar antinociceptive effects in rats. The chronic tolerance to KUST201 actions de-velops less quickly, but the abstinence scores of KUST201 are slightly higher. The activation of δ-opi-oid receptor can synergistically enhance the antinoci-ception mediated by μ-receptor.
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Dry powder inhalers (DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance. The purpose of this review is to summarize and illuminate how these factors affect drug-carrier interaction and influence the performance of DPIs.
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Objective:The purpose of the study was to evaluate and compare hand tracings on conventional lateral cephalograms with different calibration techniques available in dolphin imaging on digital lateral cephalogram. Materials and Methods:50 Conventional lateral cephalogram and 50 digital lateral cephalogram were taken in (NHP) at same period of timeon the same patient. Two angular measurements Facial Axis Angle and ANB angle two linear measurements Sella to Nasion and Sella to articulare have been taken. The digital images were traced by calibration 3 techniques Ruler, DPI and Land mark available in Dolphin Imaging Software Version 11.5.The conventional were traced on lead acetate paper and data has been collected.Results: In measurement of Facial Axis Angle conventional when compared with different calibration techniques Ruler Land Mark technique show <0.001significantvalue. In measurement of ANB angle shows no significant values. In measurement of S-N length Ruler compared with DPI has shown significant p value <0.001. DPI compared with conventional shows 0.001. S-AR length has shown significant value p value 0.006, DPI compared with Landmark shows 0.007,Landmark compared with conventional shows 0.003. Conclusion: According to our study conventional when compared with calibration techniques ruler has show only one significant value DPI and land mark has shown two significant values so our study conclude that using ruler is the better option for calibration of digital radiograph. As ruler is more accurate to conventional we compare DPI and Landmark techniques to ruler, landmark shows less variation with ruler so according to our study the second option for calibration of digital radiograph is landmark and last option comes DPI.
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Drug delivery to lungs is becoming an important means of administration of some drugs for lung disease and some protein drugs with systemic effects. This article introduces the inhalation devices and particle characteristics,the two main features of dry powder inhalers (DPI), then reviews the advances on evaluation methods in vitro and in vivo for DPI, such as next generation pharmaceutical impactor (NGI), the imitation between particles and cells using electrodynamic levitation, hydraulic lung and dry powder endotracheal insufflator device, providing references for research and development of DPI evaluation methods.
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Drug delivery to lungs is becoming an important means of administration of some drugs for lung disease and some protein drugs with systemic effects. This article introduces the inhalation devices and particle characteristics,the two main features of dry powder inhalers (DPI), then reviews the advances on evaluation methods in vitro and in vivo for DPI, such as next generation pharmaceutical impactor (NGI), the imitation between particles and cells using electrodynamic levitation, hydraulic lung and dry powder endotracheal insufflator device, providing references for research and development of DPI evaluation methods.
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OBJECTIVE: To summary the common methods that used to assay dry powder inhaler in vivo, and provide a theoretical basis and some research ideas for relative research.
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Bronchial Asthma (BA) is a chronic airway disorder with significant morbidity and mortality but due to recent advances in the field of medicine most patients with BA can have complete symptom control and live a normal life. There are various routs of drug delivery for asthma control but among them aerosol inhalation is considered the optimal route. A number of pressured Metered Dose Inhalers (MDI) & Dry Powder Inhalers (DPI) are available for this purpose. However inhalation of therapeutic aerosols is not without difficulty, it requires precise instructions on the inhaler maneuvers, which is different from spontaneous normal breathing. Also, the characteristics of the inhaler device have to be suitable for the user. Available data indicate that, lack of knowledge demonstrated by health professionals & patients on the inhalation maneuvers & handling of inhalers resulting in a reduction of therapeutic benefit. The paper reviews the literature concerning the fundamental aspects of inhaler devices, inhalation maneuvers & device selection, in an attempt to increase the knowledge of and to optimize the clinical use of therapeutic inhalers. As a result of which Asthmatics can be kept under good control.
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Background: β2 agonist administered via a nebulizer is the standard treatment for acute asthma exacerbation. There are some limitations for the use of nebulization. We conducted a study to determine the efficacy of salbutamol administered via the pMDI with Volumatic® spacer and the Easyhaler®(DPI) compared to nebulization in mild to moderate asthma exacerbations in children. Methods: A multicenter, randomized, controlled study was conducted in children between 5 and 18 years of age who presented at an emergency or outpatient department. They were randomized to receive either 6 puffs of salbutamol via the pMDI with Volumatic® spacer, or via the Easyhaler®, or 0.15 mg/kg of salbutamol nebulized via oxygen (or compressed air). The primary outcome was the clinical response which was assessed using the modified Wood’s asthma score. The secondary outcomes were: hospitalization, asthma re-visit within 3 days, systemic corticosteroid use and adverse events. The clinical score, oxygen saturation, PR, RR, BP and adverse events were recorded at time 0 (before treatment) and 20, 40 and 60 minutes after drug administration. Results: There were no statistically significant differences in the clinical response between the three groups at the 1st, 2nd or 3rd dose or for the SpO2 or the respiratory rate while the children in the Easyhaler® group had significantly less tachycardia after the 2nd dose. No significant adverse events were noted among the three groups. Conclusions: Salbutamol administered via pMDI with Volumatic® spacer or DPI (Easyhaler®) are as effective as salbutamol given via a nebulizer in providing effective relief of mild to moderate severity acute asthma exacerbation in children between 5 and 18 years of age.
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Although dietary protein restriction may protect against progression of renal failure, it is important to consider whether protein restriction can be attained without inducing malnutrition. We assessed the calculated dietary protein intake(cDPI) by 24 hour urinary collection and food intake, biochemical nutritional indices and the results of anthropometric measurement in 83 predialysis patients with different stages of chronic renal failure(CRF) and 84 controls. Dietary interventions were minimal. We categorized patients into three groups according to whether their creatinine clearance(Ccr) was greater than 25(group A), 10 to 25(group B), or less than 10ml/min(group C). 1) The mean(+/-SD) cDPI was significantly lower in group C(0.77+/-0.17g/kg/day) and group B(0.84+/- 0.16g/kg/day) than in group A(1.04+/-0.21g/kg/day) and controls(1.14+/-0.22g/kg/day)(P<0.05). The mean (+/-SD) high biologic value protein intake was significantly lower in group C(0.29+/-0.25g/kg/day) and group B(0.39+/-0.27g/kg/day) than in group A (0.48+/-0.35g/kg/day)(P<0.05). The cDPI(r=0.50, P< 0.05), high biologic value protein intake(r=0.39, P< 0.05) were positively correlated with the Ccr. 2) The mean (SD) total lymphocyte count (TLC) was significantly lower in group C(1,554+/-368/mm3) and group B(1,972+/-470/mm3) than in group A(2,111+/-540/mm3) and controls(2,177+/-589/mm3)(P<0.05). The TLC was positively correlated with the Ccr(r= 0.28, P<0.05). The levels of albumin and transferrin were lower in patients with CRF than in controls (P<0.05). There was no difference in the levels of albumin, transferrin, prealbumin, insulin-like growth factor-1, cholesterol and anthropometric measurements among the different stages of CRF. CONCLUSION: In predialysis patients with CRF, the dietary protein and high biologic value protein intake spontaneously decreases as renal function declines. Several nutritional indices, such as TLC, albumin and transferrin were lower in predialysis patient with CRF than controls. Therefore objective measurement of DPI should be considered to educate a low protein diet in predialysis patients with CRF.
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Humans , Cholesterol , Creatinine , Diet, Protein-Restricted , Dietary Proteins , Eating , Kidney Failure, Chronic , Lymphocyte Count , Malnutrition , Nutrition Assessment , Prealbumin , Renal Insufficiency , Renal Insufficiency, Chronic , TransferrinABSTRACT
0.05).Conclusion The peptide growth factors can activate the Akt kinase by phosphorylation.This process depends on the production of H2O2 and the presence of PTEN.