Oral delivery of proteins and peptides: Challenges, status quo and future perspectives

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs.

Evaluation of Serum Level of Neutrophil Elastase, Superoxide Dismutase and Nitric Oxide in COPD Patients and its Correlation with Lung Function Test.

Aims: Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death worldwide. Its prevalence is increasing in the world. Tobacco smoking is the major risk factor for COPD. Oxidant-antioxidant and protease – anti-protease imbalance is the major hallmarks for the pathogenesis of COPD. The present study was planned to assess the correlation between markers of airflow obstruction with the serum level of neutrophil elastase, nitric oxide and superoxide dismutase in COPD patients. Study Design: Case Control Study. Place and Duration of Study: Department of Biochemistry, B. J. Govt. Medical College, Pune [Maharashtra]. The study period was in between Feb.2012 to Dec. 2013. Methodology: Study comprised of 60 stable COPD patients and 60 healthy controls. COPD patients were selected as per the GOLD (Global Initiative for Obstructive Lung Disease) criteria with of aged between 40 to 75 yrs. Each subject undergone through the pulmonary function test by spirometry prior to enter in the study and predicted values of FEV1, FVC and FEV1/FVC were measured. Serum level of neutrophil elastase (NE) was analyzed using commercial available ELISA kits while serum level of nitric oxide and superoxide dismutase were measured by spectrophotometric methods. Statistical analysis was done by using SPSS software 17 version. Results: In our study we observed significantly increased levels of serum neutrophil elastase and nitric oxide and decreased level of enzymatic antioxidant superoxide dismutase (SOD) in COPD patients as compared to healthy controls. We found significant strong inverse correlation between neutrophil elastase (r=-0.604, P<0.0001) and nitric oxide (r=-0.565, P<0.0001) with FEV1% predicted and positive correlation between superoxide dismutase and FEV1% predicted (r=+0.394, P<0.001) in COPD patients. Conclusion: The present study demonstrates that the level of nitric oxide, superoxide dismutase and neutrophil elastase in serum might have played role in oxidative stress and inflammation in COPD patients. Hence, it can be concluded that the measurement of these biomarkers in serum may provide a good approach to assess the severity of the disease in COPD patients.

Hypertension Prevalence in the US Population Varies with Difference in Alpha-1 Antitrypsin Genotype: A Cross Sectional Study.

Background: The prevalence of hypertension (HTN) associated with alpha-1 antitrypsin deficiency (AATD) has been studied with indeterminate results. The aim of the study was to prospectively compare the prevalence of HTN before testing in 3 groups of individuals with subsequently normal, moderately deficient, and severely deficient genotypes of AATD with adjustment for differences in demographics and clinical variables. Methods: We performed a cross sectional study using data from the Alpha-1 Coded Testing (ACT) study. The univariate demographic and clinical factors associated with HTN were further analyzed by logistic regression analysis. Results: The prevalence of HTN was 27.2%, 20.6%, and 27.9% for individuals with normal, moderate and severe AATD, respectively (p<0.02). The prevalence of HTN increased with age and an interaction between age, alpha-1 antitrypsin deficiency genotype and HTN was identified. The relative risk of HTN among young moderately deficient individuals was 0.53 (95% CI 0.37-0.76) the risk of young PiMM and PiMS (normal genotype) individuals. There was no significant difference in the risk in older moderately deficient individuals 1.02 (95% CI 0.76-1.37) and individuals with severe AATD 1.10 (95% CI 0.71-1.68) when compared to normal genotypes. Conclusion: Moderate deficiency genotypes (PiMZ, PiSS, PiMNull) have less HTN than normal or severe deficiency genotypes, particularly in young individuals. We speculate that protease inhibitor deficiency over a lifetime allows unopposed proteolysis of vascular connective tissue.Measured comorbidities do not explain these findings. Validation of this data should occur in other AATD cohorts.

Usability of COPD u-Healthcare Services: A from Patient Experience Perspective / 대한의료정보학회지

OBJECTIVE: This study determines the usability of the experimental u-Healthcare services program by examining the prior experience of COPD patients. METHODS: A qualitative content analysis and in-depth interviews were conducted. A total of eight COPD patients with prior experience in u-Healthcare services were interviewed between August 12, 2009 and September 10, 2009. RESULTS: The participants were asked open questions on u-Healthcare services, including their general experience, major attributes, service expectations, future usage intentions, and education and training needs. The participants were also asked to indicate current healthcare inconveniences that u-Healthcare services might solve. CONCLUSION: The results of this study based on patient experience suggest the potential viability of u-Healthcare services.

Oxygen and Ventilatory Therapy and Lung Transplantation of the Chronic Obstructive Pulmonary Disease (COPD) / 한양의대학술지

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation, and in advanced COPD, peripheral airway obstruction, and pulmonary vascular abnormalities reduce the lung's capacity for gas exchange, producing hypoxemia and, later, hypercapnia. Oxygen therapy, one of the principal non-phamacologic treatments for patients with advanced COPD, can be administered in various ways. Long-term oxygen therapy improves longevity in patients with COPD who are chronically hypoxemic; it may also decrease morbidity, decrease disability, and improve handicap in some patients. A prescription for long-term oxygen therapy should outline the dose of oxygen for rest, sleep, activity, and exercise; the duration of continuous use; and the delivery devices required. Ventilatory support can be applied both invasively and noninvasively in patients with an acute exacerbation of COPD, as well as in stable COPD patients. Noninvasive ventilatory support is attractive therapy and should be tried whenever possible. Positive pressure ventilation is the mode of choice for ventilatory support, both in patients with acute exacerbation of COPD and in stable patients. In the acute situation, the main goals of ventilatory support are to reduce the work of breathing and to support gas exchange and alveolar ventilation. In appropriately selected patients with COPD, lung transplantation prolong life, improves functional capacity, and enhances the quality of life. The choice of transplantation procedure is determined on an individual basis by predetermined guidelines and experience of the individual transplantation center. However, rejection remains an obstacle to better mid-term results, and its effects on survival remain controversial.