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Faculty of Pharmacy

 

Recent Submissions

  • Karumo, Suvi (2022)
    Liposomes are biocompatible spherical nanosized vesicles consisting of hydrophobic phospholipid bilayer encasing an aqueous core. They can be utilized as drug carriers by either encapsulating molecules inside the core or embedding them in the bilayer accordingly to achieve numerous advantages such as prevention of rapid clearance and reduction of adverse effects as systemic exposure is reduced. Despite the marked efforts in designing the liposomes to improve therapeutic outcomes, only limited drug concentrations are achieved at the target sites such as in solid tumors. Stimuli-responsive liposomes could be applied as potential delivery systems to achieve spatiotemporally controlled drug delivery, i.e., the drug release could be pinpointed and restrained to the target site. In this thesis, the objective was to study the light-activated indocyanine green (ICG) liposomes as nanocarriers for peptide-based anti-tumor agents. The physicochemical characteristics, stability and functionality of the prepared liposomes were determined alongside optimizing the formulation as needed and utilizing different model peptides as encapsulated compounds. Additionally, the peptide stability during near-infrared (NIR) light illumination and the effects of the anti-angiogenic model peptides in vitro were investigated. The stability of the liposomes was assessed by monitoring the size of the liposomes, intactness of ICG, and passive leakage of the peptides over time, and by determining the phase transition temperatures of the different formulations. The liposomes remained adequately stable in different relevant conditions, and the observed phase transition temperatures did not indicate the lipid bilayer becoming permeable in physiological temperatures. However, the rate of passive leakage was rather high in all formulations, although with stiffer lipid bilayer in the “rigid” formulation, the unintended release was able to be decreased slightly in comparison to the other formulations. On the other hand, light-triggered release upon illuminating the liposomes remained considerably low in all formulations. The intactness of peptides seemed to not be impacted by the illumination. Also, no cytotoxic effects were observed after exposing human umbilical vein endothelial cells (HUVEC) to the peptides. The final “rigid” formulation showed the best functionality out of those included in the studies. It remains to be investigated whether the formulation could be improved further for optimal functionality and stability, and to what degree do the properties of the cargo molecule affect the performance of the liposomes.
  • Savola, Mirjam (2022)
    Ischemic heart disease (IHD) and subsequent heart failure are caused by irreversible loss of contractile cardiomyocytes due to low oxygen supply to the heart. As the leading cause of death worldwide, IHD raises an urgent need for regenerative therapies that prevent or reverse loss of cardiomyocytes. The fetal mammalian heart grows by cardiomyocyte proliferation and utilizes glycolysis as main energy metabolism pathway, until it is introduced to increased oxygen and fatty acid supply at birth. Subsequently, cardiac energy metabolism shifts from glycolysis to β-oxidation of fatty acids and cardiomyocytes exit the mitotic cell cycle. Due to cessation of proliferation the heart can no longer regenerate after ischemic injury and responds to it by introduction of maladaptive pathological processes leading to heart failure. To gain deeper insight on the roles of cardiac metabolism pathways and hypoxia in cell cycle activation, we evaluated the effects of pharmacological metabolic modulation and oxygen supply on cardiomyocyte phenotype and hypoxia response. Furthermore, we studied the changes in the metabolic genotype of cardiomyocytes under alterations of oxygen supply. We utilized quantitative reverse transcription PCR (qRT-PCR) to evaluate the effects of hypoxia and metabolic maturation on the expression of genes involved in hypoxia signaling and metabolism of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Additionally, we investigated the effects of five metabolism-modulating compounds on cell cycle and phenotype of both metabolically matured and unmatured hiPSC-CMs, by utilizing high content analysis. We observed presence of hypoxia signaling as an increase in vascular endothelial growth factor A (VEGFA) expression following 3-hour hypoxic exposure. High expression of succinate dehydrogenase complex flavoprotein subunit A (SDHA) in hiPSC-CMs, which was downregulated at hypoxia, confirmed occurrence of oxidative metabolism induced by metabolic maturation. Surprisingly, metabolic maturation tended to increase proliferation and decrease stress response signaling of hiPSC-CMs. Introduction of the TCA cycle intermediate succinate decreased proliferation of metabolically unmatured hypoxic hiPSC-CMs by 8.2 %. Finally, inhibition of the mevalonate pathway and ketogenesis caused no alterations in hiPSC-CM phenotype or cell cycle, but introduction of the ketone body β-hydroxybutyrate tended to increase proliferation, supporting current evidence that ketogenesis plays a role in cardiomyocyte cell cycle regulation. Our observations suggest that hypoxic hiPSC-CMs can be useful in investigating gene expression and phenotype. Even so, additional methodologies are needed for in-depth evaluation of metabolic reprogramming and its effects on cardiomyocyte phenotype.
  • Ruutiainen, Henna (2022)
    In health care, the most patient safety incidents occur from medication errors, to which pediatric patients in particular are susceptible. According to James Reason's Theory of Human Error, errors inevitably occurs in an individual's actions, causing potential harm. The prescribing phase has been identified as a specific risk point in the pediatric medication-use process, and therefore defences must be established to prevent or stop errors before they reach the patient. Such system-centric barriers are, for example, electronic health record (EHR) systems that can include computerized physician order entry (CPOE) systems where e.g., medication orders and prescriptions can be made. Knowledge-based clinical decision support (CDS) tools such as dose range check or dose calculator can be integrated into the CPOE system to assist in the prescribing process. The objective of this systematic review was examine the effects of CPOE systems with CDS functions on preventing wrong dose errors in pediatric inpatient orders and outpatient prescriptions. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 criteria and Synthesis Without Meta-analysis (SWiM) items as an extension to PRISMA criteria. The Joanna Briggs Institute’s (JBI) recommendations from JBI Manual for Evidence Synthesis on mixed methods was used as a guide to conduct this review. Additionally, Cochrane Handbook for Systematic Reviews of Interventions was utilized to conduct the synthesis examining the wrong dose error effectiveness. The study protocol according to the prior defined eligibility criteria was registered in PROSPERO. The literature search was implemented in four databases (MEDLINE Ovid, Scopus, Web of Science and EMB Reviews), reference lists and grey literature in January 2022. Two independent reviewers conducted the study selection and data extraction of the eligible studies using a Covidence software platform. Vote counting method was used to describe and analyze the quantitative findings of the studies exploring the characteristics of CPOE-CDS systems reducing wrong dose errors and regarding their effectiveness on error prevention. JBI’s critical appraisal tools and Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach were used to define the quality of the studies. A total of 18 studies met the inclusion criteria. The studies had been published in 2007–2021 and majority (13/18) considered only inpatient orders. Almost all (n=16) studies had customized or homegrown CPOE-CDS system and the most used CDS tools were dose range check (78%, 14/18), dose calculator (45%, 8/18) and dosing frequency check (45%, 8/18). When implementing new or customizing the used CPOE-CDS system usually alert functions were added (n=9) and in total alerts were present in 15 studies. Statistically significant reduction in wrong dose errors (overall, overdosing or underdosing errors) was reported in eight studies. None of the studies (n=18) found an overall increase of wrong dose errors. CPOE systems with CDS functions have a great potential to reduce wrong dose errors and promote pediatric medication safety. CPOE-CDS system customization for pediatric population, implementing CDS alerts and the use of dose range check tool seem to be most advantageous when aiming to prevent wrong dose errors. However, CPOE-CDS systems cannot prevent all wrong dose errors as human errors continue to occur and the implemented CPOE-CDS systems can pose new risks such as alert fatigue. Therefore, systematic actions are needed to optimize the safe use of CPOE-CDS systems in pediatrics. More studies are needed particularly on the effectiveness on wrong dose error prevention comparing basic and advanced CDS tools and the effects of different individual CDS functions on wrong dose errors.
  • Hietanen, Jannemarkus (2022)
    The price competition of biological medicines induced by biosimilars has started slower than expected in Europe. One of the main reasons has been the differences in physicians’ attitudes toward biosimilars. Switching biological medicines to clinically comparable alternatives is an important way to enhance the cost-effectiveness of using biological medicines. The focus of the conversation has shifted from the general similarity of biosimilars and the originators to whether frequent switching involves additional risks. The purpose of this master’s thesis was to investigate factors influencing physicians’ prescribing of biological medicines. In addition, their perceptions of the automatic substitution of biological medicines in Finland were explored. The study was based on structured personal interviews of rheumatologists and gastroenterologists including specialising physicians who work at HUS Helsinki University Hospital in the Hospital District of Helsinki and Uusimaa (n=48). They had a chance to comment on their responses at any time freely. The interview consisted of four sections: demographics, general attitudes toward biosimilars, factors affecting prescribing biological medicines, and perceptions of the automatic substitution of biological medicines. Study participants had a chance to comment on their structured responses during the interview. The interviews were recorded for further analysis of the comments. The results are based on a descriptive quantitative analysis and an inductive analysis of the comments. The interviewed physicians’ (n=27, response rate 56,3%) attitudes toward biosimilars were highly positive. Most of the physicians (21/27, 78%) also strive to motivate patients to switch biological medicines to clinically comparable but lower-cost options despite the challenges associated with switching, for example the differences in the administration devices. Of the previously determined factors, the ones affecting prescribing biological medicines the most were the willingness to support the price competition between the biological medicines, reimbursement status, and the hospital’s drug formulary when initiating the biological treatment in the hospital. The attitudes toward the automatic substitution of the biological medicines were positive among 13/27 (48 %) physicians. Our study results are in line with the results of earlier studies, but the open responses especially to the automatic substitution of biological medicines might indicate more positive perceptions on the subject among physicians in Finland.
  • Sinnemaa, Olivia (2022)
    The package leaflet (PL) is a technical document sheet included in medicine packages to provide guidance on safety and rational use of medicines for the user. The EU is increasingly encouraging the adoption of digital product information, which in time should be seen as the basic medicine information. The outdated package leaflet has for a long time been criticized by both patients and pharmaceutical operators. As a result, it is important to map the perspectives of various pharmaceutical operators on the electronic package leaflet. The aim of the study was to gain broader knowledge and deeper understanding of what opportunities and challenges the electronic package leaflet entails from the perspective of different pharmaceutical operators, and whether there are differences between opinions of the pharmaceutical operators. The study also sought to find out how the electronic package leaflet compared with the printed current leaflet from an environmental perspective. The study was conducted as a questionnaire e-survey, whose target groups were companies in the pharmaceutical industry, The Finnish Medical Agency (Fimea) and hospital pharmacies / departmental pharmacists. The material was collected over a three-week period in April 2022. The data was analysed both quantitatively and qualitatively. Based on the results of the study, it emerged that 55 experts, broadly across the pharmaceutical field, took part in the study. According to the pharmaceutical operators, the main opportunities of the electronic package leaflet were its ease of use and environmental friendliness. Patient safety, which is always a focal point when discussing medicines, would also increase as the users would have access to the most up-to-date medicine information (75 %, n = 41). In addition, the QR code on the medicine packages could be utilized when introducing ePL. The challenges, however, mainly concerned the user's lack of internet connectivity and incompetence in the use of e-services. Although pharmaceutical operators are of different opinion on the electronic package leaflet, it is highlighted that the majority of respondents (69 %, n = 38) believe that ePL would be an improvement and a more environmentally friendly alternative than the current printed leaflet. The study shown that there are differences in the perspectives on ePL between different pharmaceutical operators. The varying opinions on the electronic package leaflet depends on the respondent's position in the pharmaceutical sector. Despite the disagreement, the majority believe that ePL would be a positive development and a prerequisite for achieving the challenges of the future.