Trend analysis of the pharmaceutical market in Iran; 1997-2010; policy implications for developing countries.

BACKGROUND: So far, no detailed study of the Iranian pharmaceutical market has been conducted, and only a few studies have analyzed medicine consumption and expenditure in Iran. Pharmaceutical market trend analysis remains one of the most useful instruments to evaluate the pharmaceutical systems efficiency. An increase in imports of medicines, and a simultaneous decrease in domestic production prompted us to investigate the pharmaceutical expenditure structure. On the other hand, analyzing statistics provides a suitable method to assess the outcomes of national pharmaceutical policies and regulations. METHODS: This is a descriptive and cross-sectional study which investigates the Iranian pharmaceutical market over a 13-year period (1997-2010). This study used the Iranian pharmaceutical statistical datasheet published by the Iranian Ministry of Health. Systematic searches of the relevant Persian and English research literature were made. In addition, official government documents were analyzed as sources of both data and detailed statements of policy. RESULTS: Analysis of the Iranian pharmaceutical market in the 13-year period shows that medicine consumption sales value growth has been 28.38% annually. Determination of domestic production and import reveals that 9.3% and 42.3% annual growth, respectively, have been experienced. CONCLUSIONS: The Iranian pharmaceutical market has undergone great growth in comparison with developing countries and the pharmerging group, and the market is expanding quickly while a major share goes to biotechnology drugs, which implies the need to commercialization activities in novel fields like pharmaceutical biotechnology. This market expansion has been in favor of imported medicine in sales terms, caused by the reinforcement of suspicious policies of policy makers that necessitates fundamental rearrangements.

Method for Isolating Extracellular Vesicles from Human Neural Stem Cells Expanded Under Neurosphere Culture.

Neural stem cells (NSCs) transplantation enhances plasticity and restores functions in neurological diseases. Therapeutic benefits of NSCs are due to their ability to replace the lost neurons and glial cells and also secreting a wide array of free and membrane-bound bioactive molecules that can reduce the hostility of diseased microenvironment, resolve inflammation, and rescue damaged neural cells. Membrane-encircled spherical nanostructures that are collectively known as extracellular vesicles (EVs) contain mRNA, miRNA, lipids, and specific proteins that affect different biological processes in cells located nearby or at far distances. Using EVs as an alternative non-cell-based therapy has gained huge attention, and developing methods for large-scale production of EVs is of great clinical importance. Here, we describe an efficient method to yield significant quantity of EVs from human NSCs that are expanded under free floating neurosphere assay culture system. Using the neurosphere assay in bioreactors under GMP-compliant conditions can result in scalable NSC-EVs required for human trials.

Enrichment of the erythrocyte miR-451a in brain extracellular vesicles following impairment of the blood-brain barrier.

Extracellular RNAs (exRNAs) are present in all biofluids and incorporate many types of RNAs including miRNA. To enhance their stability outside of the cell, exRNAs are bound within ribonucleoprotein complexes or packaged into extracellular vesicles (EVs). The blood-brain barrier (BBB) is a dynamic interface between the systemic circulation and the CNS and is responsible for maintaining a stable extracellular environment for CNS cells. The intent of this study was to determine if EVs and their contents are transferred from the peripheral circulation to the CNS under conditions of an impaired BBB. The BBB of mice was disrupted by unilateral intracarotid artery infusion with hyperosmolar mannitol solution. To validate barrier opening, the uptake clearance of [13C12]-sucrose in the left forebrain (i.e. the ipsilateral, mannitol injected hemisphere) was quantified and revealed a 14-fold increase in the mannitol perfused hemisphere compared to sham treated mice. EVs were isolated from the extracellular spaces of the left forebrain following gentle tissue lysis and differential ultracentrifugation. EVs were confirmed using nanotracking analysis, electron microscopy and western blotting. qRT-PCR showed that the erythrocyte-enriched miR-451a in brain tissue EVs increased with mannitol treatment by 24-fold. Small RNA sequencing performed on the EVs isolated from the sham and mannitol treated mice showed that miR-9-5p was the most abundant miRNA contained within the brain EVs. qRT-PCR analysis of plasma EVs did not produce a statistically significant difference in the expression of the CNS-enriched miR-9-5p or miR-9-3p, suggesting that transfer of CNS EVs to the peripheral circulation did not occur under the conditions of our experiment. We demonstrate that EVs containing miR-451a, a highly abundant miRNA present within erythrocytes and erythrocyte EVs, are enhanced in the CNS upon BBB disruption.

The impact of sanction and healthcare system reform on the healthcare performance and pharmaceutical market in Iran; 2001-2016.

BACKGROUND: Iranian government has introduced multiple healthcare system reforms during the last 30 years aiming at improving accessibility and affordability of care. Pharmaceutical products are one of the major sources of financial burden on the healthcare system. The healthcare system and pharmaceutical sector have been balanced out by the partially counteracting effects of the HSEP (Health sector evolution plan) and the imposed sanctions. METHODS: This research investigates the healthcare system performance as well as the pharmaceutical market trend mostly based on the financial criteria from 2001. The correlation between the two change patterns was studied to understand the underlying driving market forces. RESULTS: During 2001 to 2013, total health expenditure has grown 25.6% in average. THE (Total health expenditure) share of the GDP remains between 6-7%, while the out of pocket payment has dropped to 37% in 2015 from 57% in 2001, and most health services been directed to the inpatient facilities. Iranian pharmaceutical market has grown rapidly in recent years and grew 28.38% per year and drug consumption per capita reached 34.43$ from 2.28$. However, the import drove most of the market expansion. Noteworthy, the share of pharmaceuticals from THE has also increased. CONCLUSIONS: It is concluded that the sanctions and HSEP have enforced partially counteracting forces on the pharmaceutical market to maintain its consistent growing trend.

Trend Analysis of Medicine Consumption Based on Therapeutic Categories in Iran: 2000-2016.

OBJECTIVE: Iranian healthcare system cost has been remarkably growing during the recent decades. Drug shortages and the economic effects of the sanctions have also exposed the pitfalls and shortcomings of the pharmaceutical system. Moreover, the pharmaceutical system is a major expenditure source for the health system. Pharmaceutical market trend analysis serves as a reliable tool to gather and analyze market and consumption data to take account of the past policies and forecast the future of the market and disease trends. METHODS: The present work tries to quantitatively describe and analyze past 17 years of Iranian pharmaceutical market sales data from 2000 to 2016. The anatomical therapeutic chemical-classified drug utilization data obtained from the Iranian Food and Drug Administration were used to analyze the market trends for each therapeutic class and categorize them. FINDINGS: The size of Iranian pharmaceutical market has grown dramatically during the last 5 years reaching to $5.183 billion in 2016 from $3.847 billion in 2011 with a compound annual growth rate of 6.14%. Antidiabetics and antineoplastic agents were one of the most prominent market growth drivers. Introduction of new drug molecules to the market has also contributed to the trend. However, the noncommunicable diseases are gaining momentum in the national disease burden. CONCLUSION: The market growth necessitates policies to prevent the overwhelming cost burden on the healthcare system which in turn requires well-informed decision-making. Pharmaceutical market trend analysis tries to supply the evidence feed for informed policy-making to forecast, prioritize, and contain the cost burden imposed on the healthcare system by the pharmaceutical sector.

Optimization of rPDT fusion protein expression by Escherichia coli in pilot scale fermentation: a statistical experimental design approach.

High yield recombinant protein production is highly desirable for biotechnological purposes. In the design of recombinant expression conditions, a number of essential central elements such as expression strain, type of medium, bioprocess optimization, and mathematical modeling should be considered. Well-designed industrial scale production of one recombinant protein with optimized influential parameters and yield can address the cost and production reproducibility issues. In the present study, statistical experimental design methodology was used to investigate the effect of fermentation conditions (dissolved oxygen, IPTG, and temperature) on rPDT production by Escherichia coli. rPDT is a recombinant fusion protein consisting of three different protein domains including the N-terminal 179 amino acid fragment of the S1 subunit of pertussis toxin, the full-length genetically detoxified diphtheria toxin (CRM197), and the 50 kDa tetanus toxin fragment C. A 15 Box-Behnken design augmented with center points revealed that IPTG and DO at the center point and low temperature will result in high yield. The optimal condition for rPDT production were found to be 100 µM IPTG, DO 30% and temperature 20 °C.