Improve Drug Therapy Research Articles

Medication Reconciliation as Part of Admission Management-A Survey to Improve Drug Therapy Safety in a Urology Department.

Complete medication reconciliation during hospital admission is the rationale for further treatment decisions. A consecutive, controlled intervention study was conducted to assess discrepancies in medication reconciliation performed by nurses of the Urology Department compared to the Best Possible Medication History (BPMH) established by pharmacists. This study included pre-intervention (control group, CG), nursing training as a pharmaceutical intervention, and post-intervention (intervention group, IG) groups. The discrepancies were classified as "Missing" (not recorded but taken), "Added" (additionally recorded) "Strength" (incorrect documented dosage), "Intake" (incorrect intake time/schedule), "Double" (double prescription), and "Others" (no clear assignment). Additionally, high-risk drug subgroup discrepancies were particularly prevalent and were evaluated. Training success was compared concerning discrepancies in the CG and IG. Generally, the percentage of discrepancies per patient found was lower in the IG than in the CG (78.1% vs. 87.5%, significantly). The category most identified was "Missing" (IG, 33.3% vs. CG, 35.2%). Overall, a discrepancy of 7.4% each (discrepancies: IG, 27 vs. CG, 38) was determined for high-risk drugs while "Missing" occurred (77.8% vs. 52.6%, out of 7.4%). Despite nursing training only partially reducing discrepancies, the implementation of medication reconciliation using BPMH by pharmacists could improve the process, especially for high-risk drugs.

Overcoming Barriers: Strategies for Implementing Pharmacist-Led Pharmacogenetic Services in Swiss Clinical Practice.

There is growing evidence that pharmacogenetic analysis can improve drug therapy for individual patients. In Switzerland, pharmacists are legally authorized to initiate pharmacogenetic tests. However, pharmacogenetic tests are rarely conducted in Swiss pharmacies. Therefore, we aimed to identify implementation strategies that facilitate the integration of a pharmacist-led pharmacogenetic service into clinical practice. To achieve this, we conducted semi-structured interviews with pharmacists and physicians regarding the implementation process of a pharmacist-led pharmacogenetic service. We utilized the Consolidated Framework for Implementation Research (CFIR) to identify potential facilitators and barriers in the implementation process. Additionally, we employed Expert Recommendations for Implementing Change (ERIC) to identify strategies mentioned in the interviews and used the CFIR-ERIC matching tool to identify additional strategies. We obtained interview responses from nine pharmacists and nine physicians. From these responses, we identified 7 CFIR constructs as facilitators and 12 as barriers. Some of the most commonly mentioned barriers included unclear procedures, lack of cost coverage by health care insurance, insufficient pharmacogenetics knowledge, lack of interprofessional collaboration, communication with the patient, and inadequate e-health technologies. Additionally, we identified 23 implementation strategies mentioned by interviewees using ERIC and 45 potential strategies using the CFIR-ERIC matching tool. In summary, we found that significant barriers hinder the implementation process of this new service. We hope that by highlighting potential implementation strategies, we can advance the integration of a pharmacist-led pharmacogenetic service in Switzerland.

Unveiling Pharmacokinetics and Drug Interaction of Linagliptin and Pioglitazone HCl in Rat Plasma Using LC-MS/MS.

The linagliptin (LIN) and pioglitazone HCl (PIO) combination, currently undergoing phase III clinical trials for diabetes mellitus treatment, demonstrated significant improvements in glycemic control. However, the absence of an analytical method for simultaneous determination in biological fluids highlights a crucial gap. This underscores the pressing need for sensitive bioanalytical methods, emphasizing the paramount importance of developing such tools to advance diabetes management strategies and enhance patient care. Herein, a sensitive reverse-phase high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for simultaneous determination of LIN and PIO in rat plasma using alogliptin as an internal standard. Chromatographic separation was performed on an Agilent Eclipse Plus C18 (4.6 × 100 mm, 3.5 μm) using an isocratic mobile phase system consisting of ammonium formate (pH 4.5) and methanol using an acetonitrile-induced protein precipitation technique for sample preparation. Multiple reaction monitoring in positive ion mode was used for quantitation of the precursor to production at m/z 473.2 → 419.9 for LIN, 357.1 → 134.2 for PIO, and 340.3 → 116.1 for ALO. The linearity range was 0.5 to 100 and 1 to 2000 ng/mL for LIN and PIO, respectively. The developed method was validated as per US-FDA guidelines and successfully applied to clinical pharmacokinetic and drug-drug interaction studies with a single oral administration of LIN and PIO in rat plasma. Pharmacokinetic parameters of LIN were significantly influenced by the concomitant administration of PIO and vice versa. Molecular modeling revealed the significant interaction of LIN and PIO with P-glycoprotein. Therefore, the drug-drug interaction between LIN and PIO deserves further study to improve drug therapy and prevent dangerous adverse effects.

Linking Disulfide Levels and NAD+ Metabolism with Alzheimer's Disease for Diagnostic Modeling and Target Drug Analysis.

Alzheimer's disease (AD) is a condition that affects the nervous system and that requires considerably more in-depth study. Abnormal Nicotinamide Adenine Dinucleotide (NAD+) metabolism and disulfide levels have been demonstrated in AD. This study investigated novel hub genes for disulfide levels and NAD+ metabolism in relation to the diagnosis and therapy of AD. Data from the gene expression omnibus (GEO) database were analyzed. Hub genes related to disulfide levels, NAD+ metabolism, and AD were identified from overlapping genes for differentially expressed genes (DEGs), genes in the NAD+ metabolism or disulfide gene sets, and module genes obtained by weighted gene co-expression network analysis (WGCNA). Pathway analysis of these hub genes was performed by Gene Set Enrichment Analysis (GSEA). A diagnostic model for AD was constructed based on the expression level of hub genes in brain samples. CIBERSORT was used to evaluate immune cell infiltration and immune factors correlating with hub gene expression. The DrugBank database was also used to identify drugs that target the hub genes. We identified 3 hub genes related to disulfide levels in AD and 9 related to NAD+ metabolism in AD. Pathway analysis indicated these 12 genes were correlated with AD. Stepwise regression analysis revealed the area under the curve (AUC) for the predictive model based on the expression of these 12 hub genes in brain tissue was 0.935, indicating good diagnostic performance. Additionally, analysis of immune cell infiltration showed the hub genes played an important role in AD immunity. Finally, 33 drugs targeting 10 hub genes were identified using the DrugBank database. Some of these have been clinically approved and may be useful for AD therapy. Hub genes related to disulfide levels and NAD+ metabolism are promising biomarkers for the diagnosis of AD. These genes may contribute to a better understanding of the pathogenesis of AD, as well as to improved drug therapy.

Efficacy of Liposomal Bupivacaine in Reducing Opioid Use After Posterior Lumbar Spinal Decompression and Fusion.

Despite improvements in drug therapy and treatment of lumbar spinal disorders, dependence on opioid medication for postoperative pain control remains a concern nationwide. This study assessed the ability to diminish the reliance on opioid medication postoperatively with the Food and Drug Administration-approved local anesthetic liposomal bupivacaine in open posterior lumbar decompression and fusion procedures. In addition, the possible effects of this modality on other parameters were studied regarding patients and their recovery. A retrospective chart review of 198 patients who underwent an open posterior lumbar laminectomy and fusion surgery with instrumentation treated by a single surgeon in a single institution was conducted. Ninety-nine patients who received liposomal bupivacaine administered intraoperatively were then matched by age, sex, and procedure with the same number of patients treated prior to the availability of liposomal bupivacaine. We evaluated how the use of liposomal bupivacaine affected the requirement for postoperative opioid medication, as well as related changes in length of stay, the use of antiemetics, and urinary retention postoperatively. The patients who received liposomal bupivacaine required less than half of the morphine milligram equivalents of narcotic medications during their hospital stay compared with patients who did not receive liposomal bupivacaine (approximately 57% reduction). The findings of this study suggest that the addition of liposomal bupivacaine to traditional pain management modalities can augment pain management for patients undergoing posterior lumbar surgery, as evidenced by the significant decrease in postoperative morphine milligram equivalents required. [Orthopedics. 2024;47(4):244-248.].

A study to Monitor Adverse drug reactions in a patients of Chronic Obstructive pulmonary Disease

Background: Inappropriate drug usage may preclude ideal benefit due to increased medical cost, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). The present study aimed at assessing the current drug practice and ADEs in COPD management in ICU. Material and Methods: A prospective, single centered, observational and open labeled study was carried out in Department of Pulmonary Medicine and Pharmacology, Tertiary Care Teaching Hospital. The patient population was broadly divided into four categories based on diagnosis ‑ chronic obstructive pulmonary disease, Infections, Asthma and Others. Suspected ADRs were reported, analyzed, and causality assessment was carried out using Naranjo’s algorithm scal0065. Results: In our study, most important causative drug was Budesonide (11.1%). Causality assessment of ADR by Naranjo’s algorithm showed 11.9% probable and 88.1% possible reactions. According to WHO-UMC scale, 85.9% reactions are possible, 11.1% are probable, and 3% are unlikely. Among the 270 ADR reported, the most common ADR was oral thrush which accounted for 11.1% (n = 30) of the reported cases, followed by palpitation 11.1% (n = 30), sore throat 20 (7.4%), dizziness 17 (6.3%) cases, and headache 20 (7.4%) of reported ADR cases. Conclusion: Many research have been conducted separately on various respiratory diseases such as COPD, tuberculosis, asthma, respiratory tract infections (upper/lower), and so on. However, this study included some of the most common diseases in this field, such as COPD, tuberculosis, and respiratory tract infections. A routine patient follow-up is needed for the early detection and prevention of ADRs in order to improve patient adherence to drug therapy and provide improved drug therapy by avoiding associated morbidity and mortality.

Advanced Drug Carriers: A Review of Selected Protein, Polysaccharide, and Lipid Drug Delivery Platforms.

Studies on bionanocomposite drug carriers are a key area in the field of active substance delivery, introducing innovative approaches to improve drug therapy. Such drug carriers play a crucial role in enhancing the bioavailability of active substances, affecting therapy efficiency and precision. The targeted delivery of drugs to the targeted sites of action and minimization of toxicity to the body is becoming possible through the use of these advanced carriers. Recent research has focused on bionanocomposite structures based on biopolymers, including lipids, polysaccharides, and proteins. This review paper is focused on the description of lipid-containing nanocomposite carriers (including liposomes, lipid emulsions, lipid nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers), polysaccharide-containing nanocomposite carriers (including alginate and cellulose), and protein-containing nanocomposite carriers (e.g., gelatin and albumin). It was demonstrated in many investigations that such carriers show the ability to load therapeutic substances efficiently and precisely control drug release. They also demonstrated desirable biocompatibility, which is a promising sign for their potential application in drug therapy. The development of bionanocomposite drug carriers indicates a novel approach to improving drug delivery processes, which has the potential to contribute to significant advances in the field of pharmacology, improving therapeutic efficacy while minimizing side effects.

Supramolecular assembly of isomeric SN-38 prodrugs regulated by conjugation sites.

Supramolecular polymers (SPs) are an emerging class of drug transporters employed to improve drug therapy. Through the rational design of self-assembling monomers, one can optimize the properties of the resulting supramolecular nanostructures, such as size, shape, surface chemistry, release, and, therefore, biological fates. This study highlights the design of isomeric SN38 prodrugs through the conjugation of hydrophilic oligo(ethylene glycol) (OEG) with hydroxyls at positions 10 and 20 on hydrophobic SN-38. Self-assembling prodrug (SAPD) isomers 10-OEG-SN38 and 20-OEG-SN38 can self-assemble into giant nanotubes and filamentous assemblies, respectively, via aromatic associations that dominate self-assembly. Our study reveales the influence of modification sites on the assembly behavior and ability of the SN38 SAPDs, as well as drug release and subsequent in vitro and in vivo antitumor effects. The SAPD modified at position 20 exhibits stronger π-π interactions among SN38 units, leading to more compact packing and enhanced assembly capability, whereas OEG at position 10 poses steric hindrance for aromatic associations. Importantly, owing to its higher chemical and supramolecular stability, 20-OEG-SN38 outperforms 10-OEG-SN38 and irinotecan, a clinically used prodrug of SN38, in a CT26 tumor model, demonstrating enhanced tumor growth inhibition and prolonged animal survival. This study presents a new strategy of using interactions among drug molecules as dominating features to create supramolecular assemblies. It also brings some insights into creating effective supramolecular drug assemblies via the engineering of self-assembling building blocks, which could contribute to the optimization of design principles for supramolecular drug delivery systems.

Joint recommendations on cost calculation and estimation in paediatric clinical trials.

The conduct of clinical trials in paediatrics is essential to improve drug therapy in children. In Europe, paediatric clinical trials have been supported by the European Paediatric Regulation since 2007, but there is still a great need for high-quality clinical trials. The personnel and time required to conduct clinical trials in accordance with EU Regulations 536/2014 and 745/2017 is considerably higher compared to other studies, such as observational studies. It is important that this additional workload for the trial centre is fully compensated, also taking into account EU state aid rules. In paediatric trials, it is necessary to take into account the special requirements of paediatric and adolescent medicine when calculating the additional costs. Within the framework of the pan-European paediatric study network c4c/GermanNetPaeT, a working group dealt with specific aspects of cost calculation in order to support paediatric study centres in internal cost calculation as well as in the subsequent preparation of financing requirements for industrial sponsors or public funders. In several workshops the working group developed a cost calculation template with the content derived from the "Joint recommendations for a total services account as a factor in simplifying contracts" of the Deutsche Hochschulmedizin (DHM, German University Medicine), the Netzwerk der Koordinierungszentren für Klinische Studien (KKS Network, Network of Coordinating Centres for Clinical Trials) and the Verband Forschender Arzneimittelhersteller (vfa, German Association of Research-Based Pharmaceutical Companies). By estimating the specific time required for measures and investigations as part of a sample study, the background to the increased time required was discussed and a list with aspects to be considered for cost calculation was compiled together with the study centres. The paediatrics-specific aspects mentioned in detail are intended to increase understanding of the particular problem of higher costs for clinical trials involving children and adolescents and the need for correspondingly appropriate remuneration. This transparent and comprehensible presentation of the higher financial requirements for both the study centres and the financial supporters is intended to promote the high-quality conduct of clinical trials in paediatric study centres in the long term.

Method of treatment of trigeminal neuralgia in the elderly

The treatment of trigeminal neuralgia (HTN) in the elderly, highlighted in the literature, reflects the dissatisfaction of clinicians with the results of the treatment of this chronic disease. Scientific research on the treatment of trigeminal neuralgia in the elderly is carried out by improving drug therapy through the introduction of new drugs and their combinations and through the development of new surgical techniques that affect the trigeminal nerve system (TN). Each of the therapeutic methods is mainly aimed at a single link in the pathogenetic chain of the development of trigeminal neuralgia, either to increase the threshold of excitability of sensitized neurons of the brain stem and cortex or to turn off the trigger zone.

Prescribing of valproate and oral antiepileptics for women of childbearing age and during pregnancy in Germany between 2010 and 2020.

To examine prescriptions of valproate and oral antiepileptic drugs (OAED) in Germany irrespective of the indication in women in general and particularly in women of childbearing age (13-49 years) and during pregnancy between 2010 and 2020, that is, before, during and after the implementation of the EU risk minimization measures (RMMs). Analysis of claims data. all women continuously insured with the AOK health insurance fund in the respective observation year (2010-2020) and the previous year. OAED were identified by ATC code N03. Period of pregnancy was calculated based on birth information in claims data. (i) prevalent use of valproate/OAED: number of women with at least one prescription of valproate/OAED per year divided by all women of the study population (rate per 1000 women); (ii) percentage of OAED recipients with at least one valproate prescription during pregnancy (13-49 years) in the respective observation year. Prevalence rate/1000 women for valproate use decreased by -31.33% across all age groups (2010-2014: -7.48%; 2014-2018: -16.47%; 2018-2020: -11,17%) with a strong reduction in women 13-49 years between 2014 and 2018 (-28.74%). The rate for OAED across all age groups rose from 33.43/1000 women in 2010 to 41.03/1000 (+22,73%). Valproate use during pregnancy of women with OAED declined from 1.29% in 2010 to 0.59% in 2020 (-54,26%) (2010-2014: -5.14%; 2014-2018: -42.31%; 2018-2020: -16.69%). Even if, due to the descriptive nature of the study, no causal relationship can be postulated between the RMMs and the strong decrease in valproate prescriptions, our results are compatible with the hypothesis that the measures have improved drug therapy safety.

Function and Role of Histamine H1 Receptor in the Mammalian Heart.

Histamine can change the force of cardiac contraction and alter the beating rate in mammals, including humans. However, striking species and regional differences have been observed. Depending on the species and the cardiac region (atrium versus ventricle) studied, the contractile, chronotropic, dromotropic, and bathmotropic effects of histamine vary. Histamine is present and is produced in the mammalian heart. Thus, histamine may exert autocrine or paracrine effects in the mammalian heart. Histamine uses at least four heptahelical receptors: H1, H2, H3 and H4. Depending on the species and region studied, cardiomyocytes express only histamine H1 or only histamine H2 receptors or both. These receptors are not necessarily functional concerning contractility. We have considerable knowledge of the cardiac expression and function of histamine H2 receptors. In contrast, we have a poor understanding of the cardiac role of the histamine H1 receptor. Therefore, we address the structure, signal transduction, and expressional regulation of the histamine H1 receptor with an eye on its cardiac role. We point out signal transduction and the role of the histamine H1 receptor in various animal species. This review aims to identify gaps in our knowledge of cardiac histamine H1 receptors. We highlight where the published research shows disagreements and requires a new approach. Moreover, we show that diseases alter the expression and functional effects of histamine H1 receptors in the heart. We found that antidepressive drugs and neuroleptic drugs might act as antagonists of cardiac histamine H1 receptors, and believe that histamine H1 receptors in the heart might be attractive targets for drug therapy. The authors believe that a better understanding of the role of histamine H1 receptors in the human heart might be clinically relevant for improving drug therapy.

The EURO-FORTA (Fit fOR The Aged) List Version 2: Consensus Validation of a Clinical Tool for Improved Pharmacotherapy in Older Adults.

The aging of our societies leads to a higher prevalence of multimorbidity and therefore polypharmacy, which often results in inappropriate drug treatment. To address this issue, numerous listing approaches, such as the Fit fOR The Aged (FORTA) list have been developed. FORTA's positive impact on the quality of medications and relevant clinical outcomes has been shown. Based on new emerging evidence and experiences with the existing FORTA lists, we aimed to update the FORTA lists in several European countries/regions. Two-step Delphi consensus procedures were conducted in Poland, UK/Ireland, Italy, Spain, the Nordic countries, The Netherlands and France. The existing European FORTA lists served as survey proposals. Thirty-two experts agreed to take part in this study (return rate: 96.9%). The country/region-specific overall consensus for all items and participants after the first round was >90%. FORTA lists from six participating countries, plus the FORTA list for the German-speaking countries, were collated into the new EURO-FORTA List, which now contains 267 items aligned to 27 indications. Three items were added to the EURO-FORTA List, and no drugs were deleted. Eight FORTA items were relabeled, and 96.9% of the labels remained unchanged. In this study, seven new country/region specific FORTA lists, as well as a new overarching EURO-FORTA List, were developed. An overall increase in the mean consensus coefficient and increases for all disease-specific mean consensus coefficients show a wider consensus among participants. The new lists have the potential to improve drug therapy in older people internationally.

Predictive significance of HIF-1α, Snail, and PD-L1 expression in breast cancer.

Currently, the prediction of breast cancer (BC) effectiveness to drug treatment is based on determining the expression level of steroid hormone receptors and human epidermal growth factor receptor type 2 (HER2). However, significant differences in individual response to drug treatment require the search for new predictive markers. Here, by comprehensively examining HIF-1α, Snail, and PD-L1 expression in BC tumor tissue, we demonstrate that high levels of these markers correlate with unfavorable factors of BC prognosis: the presence of regional and distant metastases and lymphovascular and perineural invasion. Analyzing the predictive significance of markers, we show that the most significant predictors of chemoresistant HER2-negative BC are a high PD-L1 level and a low Snail level, while in HER2-positive BC, only a high PD-L1 level is an independent predictor of chemoresistant BC. Our results suggest that using immune checkpoint inhibitors in these groups of patients may improve drug therapy effectiveness.

Biomarkers: Role and Scope in Neurological Disorders.

Neurological disorders pose a great threat to social health and are a major cause for mortality and morbidity. Effective drug development complemented with the improved drug therapy has made considerable progress towards easing symptoms associated with neurological illnesses, yet poor diagnosis and imprecise understanding of these disorders has led to imperfect treatment options. The scenario is complicated by the inability to extrapolate results of cell culture studies and transgenic models to clinical applications which has stagnated the process of improving drug therapy. In this context, the development of biomarkers has been viewed as beneficial to easing various pathological complications. A biomarker is measured and evaluated in order to gauge the physiological process or a pathological progression of a disease and such a marker can also indicate the clinical or pharmacological response to a therapeutic intervention. The development and identification of biomarkers for neurological disorders involves several issues including the complexity of the brain, unresolved discrepant data from experimental and clinical studies, poor clinical diagnostics, lack of functional endpoints, and high cost and complexity of techniques yet research in the area of biomarkers is highly desired. The present work describes existing biomarkers for various neurological disorders, provides support for the idea that biomarker development may ease our understanding underlying pathophysiology of these disorders and help to design and explore therapeutic targets for effective intervention.

Nature-inspired nanocarriers for improving drug therapy of atherosclerosis.

Atherosclerosis (AS) has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation, primarily causing disability and mortality globally. Drug therapy remains the main treatment for AS. However, a series of obstacles hinder effective drug delivery. Nature, from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment, offers compelling solutions for efficient drug delivery. Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components, such as lipids, proteins and membrane structures, have emerged as promising candidates for fulfilling drug delivery needs. These nanocarriers offer several advantages, including prolonged blood circulation, targeted plaque delivery, targeted specific cells delivery and controlled drug release at the action site. In this review, we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy. Finally, we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.

ПОСТГАСТРОРЕЗЕКЦИОННЫЕ СИНДРОМЫ

The article gives a description of the section of diseases of the operated stomach – post-gastroresection syndromes. It has been noted that over the past decades the number of resection interventions due to complicated gastroduodenal ulcer has decreased. This was facilitated by the improvement of drug therapy, the emergence of new antiulcer drugs, including proton pump inhibitors, and the improvement of endoscopic methods for diagnosing and treating this pathology. Therefore, the number of post-gastroresection syndromes remains significant. The paper describes the ethology, pathogenesis, clinical manifestations of postgastrectomy syndromes. Diagnostic methods using the X-ray method, esophagogastroduodenoscopy, ultrasound examination of the abdominal organs, and computed tomography are considered in detail. Methods of conservative therapy are described, indications for surgical treatment are determined. The characteristic of classical and new methods of performing operational aids is given, and an assessment of their effectiveness is given.

Improving Drug Therapy for Pediatric Patients: Unfinished History of Pediatric Drug Development.

Improving Drug Therapy for Pediatric Patients: Unfinished History of Pediatric Drug Development.

Study protocol of the HD-MED study aiming to personalize drug treatment in Huntington's disease: a longitudinal, observational study to assess medication use and efficacy in relation to pharmacogenetics.

Huntington's disease (HD) is a hereditary, neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Currently, HD can only be managed symptomatically, including a large variety of prescribed drugs. Many HD patients experience negative medication effects (e.g. side effects or non-response). Pharmacogenetic (PGx) studies show how genetic variation affects both medication efficacy and toxicity and holds the potential to improve these outcomes of drug treatment. To classify the effect of the PGx profile of CYP2C19 and CYP2D6 in HD gene expansion carriers on negative medication effects of HD-related medication. Multicenter, observational study with 1-year follow-up. Adult HD gene expansion carriers who use one or more HD-related medications are eligible to participate. A detailed overview of medication use, medication efficacy, and side effects is retrospectively and prospectively collected via medication diaries, questionnaires, phone calls, and pharmacy medication verification schemes. PGx analysis on whole blood-extracted DNA is performed with Agena Bioscience VeriDose® Core Panel and long-range polymerase chain reaction copy number variation analysis. Per the study protocol-defined negative medication effects in HD gene expansion carriers with a genotype predicted poor or ultrarapid metabolizer phenotype will be compared with HD gene expansion carriers with a predicted intermediate and normal metabolizer phenotype. Frequencies will be analyzed via χ2 and logistic multivariate regression analysis. In addition, we summarize in this manuscript HD-relevant PGx prescription recommendations to improve drug therapy. The original study protocol was approved by the medical research ethics committee Leiden Den Haag Delft on 26 November 2019. HD-MED is a low-risk study that will generate personalized PGx results that can immediately be implemented in clinical practice, thus potentially improving pharmacovigilance and patients' quality of life. This study is registered in the International Clinical Trial Registry Platform under registration number NL8251, URL https://trialsearch.who.int/Trial2.aspx?TrialID=NL8251.

Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine

BackgroundNanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems. MethodsBiophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed. ResultsLysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs. ConclusionsWe conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes. General significanceThis investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.