Virus-Derived Peptides for Hepatic Enzyme Delivery

Lysosomal Storage Disorders (LSDs), also known as lysosomal diseases (LDs) are a group of serious genetic diseases characterized by not only the accumulation of non-catabolized compounds in the lysosomes due to the deficiency of specific enzymes which usually eliminate these compounds, but also by trafficking, calcium changes and acidification. LDs mainly affect the central nervous system (CNS), which is difficult to reach for drugs and biological molecules due to the presence of the blood-brain barrier (BBB). While some therapies have proven highly effective in treating peripheral disorders in LD patients, they fail to overcome the BBB. Researchers have developed many strategies to circumvent this problem, for example, by creating carriers for enzyme delivery, which improve the enzyme’s half-life and the overexpression of receptors and transporters in the luminal or abluminal membranes of the BBB. This review aims to successfully examine the strategies developed during the last decade for the treatment of LDs, which mainly affect the CNS. Among the LD treatments, enzyme-replacement therapy (ERT) and gene therapy have proven effective, while nanoparticle, fusion protein, and small molecule-based therapies seem to offer considerable promise to treat the CNS pathology. This work also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of LDs. Polymeric nanoparticles and liposomes are explored from their technological point of view and for the most relevant preclinical studies showing that they are excellent choices to protect active molecules and transport them through the BBB to target specific brain substrates for the treatment of LDs.

Download Full-text

Associations of CYP2A6 Gene Polymorphism with Smoking Status Among Jordanians: Gender-Related Differences

Current Drug Metabolism ◽

10.2174/1389200220666190827161112 ◽

2019 ◽

Vol 20 (9) ◽

pp. 765-770 ◽

Cited By ~ 1

Author(s):

Hana M. Hammad ◽

Amer Imraish ◽

Belal Azab ◽

Al M. Best ◽

Yousef S. Khader ◽

...

Keyword(s):

Cytochrome P450 ◽

Genetic Polymorphism ◽

Smoking Status ◽

Hepatic Enzyme ◽

Nicotine Metabolism ◽

Significant Frequency ◽

Cytochrome P450 2A6 ◽

Study Population ◽

Major Metabolic Pathway ◽

Cyp2a6 Gene

Background: Cytochrome P450 2A6 enzyme (CYP2A6), an essential hepatic enzyme involved in the metabolism of drugs, is responsible for a major metabolic pathway of nicotine. Variation in the activity of polymorphic CYP2A6 alleles has been implicated in inter-individual differences in nicotine metabolism. Aims: The objective of the current study was to assess the association between the smoking status and the cytochrome P450 2A6 enzyme (CYP2A6) genotype in Jordanians. Methods: In the current study, 218 (117 Male and 101 female) healthy unrelated Jordanian volunteers were recruited. CYP2A6*1B, CYP2A6*4 and CYP2A6*9 were determined and correlated with subject smoking status. Results: *1A/*1A was the most common genetic polymorphism in the overall study population, with no significant frequency differences between smokers and non-smokers. When the population was divided according to gender, only male smokers showed a significant correlation between genotype and smoking status. Considering the CYP2A6*9 genotype, the results showed differences in distribution between smokers and non-smokers, but only women showed a significant association between CYP2A6*9 allele genotype and smoking status. Conclusion: The results of this study show that there is a significant association between CYP2A6*9 genotype and smoking status. They also show that CYP2A6 genotype is significantly influenced by gender.

Download Full-text

Sleeve Gastrectomy Is Associated with a Greater Reduction in Plasma Liver Enzymes Than Bypass Surgeries—A Registry-Based Two-Year Follow-Up Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10051144 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1144

Author(s):

Shira Azulai ◽

Ronit Grinbaum ◽

Nahum Beglaibter ◽

Shai Meron Eldar ◽

Moshe Rubin ◽

...

Keyword(s):

Gastric Bypass ◽

Sleeve Gastrectomy ◽

Fatty Liver Disease ◽

Laboratory Tests ◽

Liver Enzymes ◽

Liver Pathology ◽

Hepatic Enzyme ◽

Demographic Information ◽

Post Surgery

Bariatric surgeries may lead to an improvement in metabolic fatty liver disease, and a reduction in the levels of the hepatic enzyme Alanine Aminotransferase (ALT). We compared the effects of Sleeve Gastrectomy (SG), Roux en Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) on the levels of ALT by analysis of two-year follow-up data from 4980 patients in the Israeli Bariatric Registry that included laboratory tests and demographic information. Pre-operative characteristics of patients, and particularly levels of liver enzymes, were similar across surgery types. Regression modeling and retrospective matching showed that SG was superior to RYGB and OAGB in reducing ALT levels, and in reducing the fraction of patients with abnormally high ALT levels. Two-year post-surgery, an increase in ALT levels from normal to abnormal levels was observed in 5% of SG patients, and in 18% and 23% of RYGB and OAGB patients. In conclusion, SG leads to a greater reduction in ALT levels compared with bypass surgeries and a lower incidence of post-surgical elevation of ALT levels. Further studies are required to identify the cause for the rise in liver enzymes, and to determine whether ALT levels correlate with liver pathology especially following bariatric surgery.

Download Full-text

Bluetongue Virus Particles as Nanoreactors for Enzyme Delivery and Cancer Therapy

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.0c01053 ◽

2021 ◽

Author(s):

Eva C. Thuenemann ◽

Duc H. T. Le ◽

George P. Lomonossoff ◽

Nicole F. Steinmetz

Keyword(s):

Cancer Therapy ◽

Bluetongue Virus ◽

Virus Particles ◽

Enzyme Delivery

Download Full-text

Decreased Wait Time and Increased Satisfaction With Bedside Pancreatic Enzyme Dosing for the Inpatient Adolescent With Cystic Fibrosis: A Quality Improvement Project Comparing Enzyme Self-Administration to Nurse Administration

Journal of Patient Experience ◽

10.1177/2374373520981490 ◽

2021 ◽

Vol 8 ◽

pp. 237437352098149

Author(s):

Brandi Middour-Oxler ◽

Margaret Gettis ◽

Betsy Dye

Keyword(s):

Cystic Fibrosis ◽

Pancreatic Enzyme ◽

Wait Time ◽

Self Administration ◽

Nurse Satisfaction ◽

Improvement Project ◽

Hospital Unit ◽

Pediatric Inpatient ◽

Inpatient Adolescent ◽

Enzyme Delivery

For children with cystic fibrosis (CF), enzymes are essential with meals to absorb nutrients and ensure adequate growth. When hospitalized, CF patients typically rely on nurse-administered medications. Recently, a pediatric hospital unit began allowing adolescents with CF enzymes at the bedside. Postimplementation, a satisfaction questionnaire was administered to participating patients and nurses measuring patient and nurse satisfaction with access to bedside enzymes versus nurse administration and overall time for enzyme delivery. The survey utilized a 5-point Likert scale. The wait time for pancreatic enzymes decreased for self-administered enzymes when compared to those that were nurse administered. All (11/11) patients and 86% (12/14) of nurses preferred the self-administration of enzymes. Hospitalized pediatric CF patients and nurses had higher levels of satisfaction with enzyme self-administration. Immediate access to enzymes in room safes impact patient autonomy, reflecting home self-care practices. Decreases in wait times optimize nutritional growth and healing while hospitalized. As a result, a new limited scope policy allowing patient-administered enzymes is now in place in the pediatric inpatient CF unit.

Download Full-text