Alternative Administration Research Articles

Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs.

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

The Effectiveness of Intranasal Midazolam for the Treatment of Prehospital Pediatric Seizures: A Non-inferiority Study

Background: Intranasal (IN) midazolam allows for rapid, painless treatment of pediatric seizures in the prehospital setting and may be a preferred administration route if determined to be non-inferior to intravenous (IV) or intramuscular (IM) routes. We sought to evaluate the effectiveness of IN midazolam for terminating prehospital pediatric seizures compared to midazolam administered by alternate routes. Methods: We performed a retrospective, non-inferiority analysis using data from a regional Emergency Medical Services (EMS) database. We included pediatric patients ≤ 14 years treated with midazolam (0.1 mg/kg) by EMS for non-traumatic seizures. The primary outcome was the proportion of patients requiring redosing of midazolam after initial treatment with IN midazolam compared to those that received IV or IM midazolam. We established a priori a risk difference of 6.5% as the non-inferiority margin. Results: We evaluated outcomes from 2,034 patients (median age 6 years [interquartile range 3 − 10 years], 55% male). Initial administration routes were 461 (23%) IN, 547 (27%) IM, 1024 (50%) IV, and 2 (0.1%) intraosseous (IO). Midazolam redosing occurred in 116 patients (25%) who received IN midazolam versus 222 patients (14%) treated initially with midazolam via alternate routes (risk difference 11% [95%CI 7 − 15%]). The age-adjusted odds ratio for redosing midazolam after intranasal administration compared to alternate route administration was 2.0 (95% CI 1.6 − 2.6). Conclusion: Prehospital treatment of pediatric seizure with intranasal midazolam was associated with increased frequency of redosing compared to midazolam administered by other routes, suggesting that 0.1 mg/kg is a subtherapeutic dose for intranasal midazolam administration.

Impact of the Injectable Opioid Drug Shortage on Analgesia and Sedation Management in the Medical Intensive Care Unit: A Retrospective Cohort Study.

Objectives: The purpose of this study was to assess the impact of the injectable opioid drug shortage on analgesia and sedation management in the medical intensive care unit (MICU). Methods: A single-center, retrospective cohort study was conducted of mechanically ventilated patients during the injectable opioid shortage. Outcomes were compared between a cohort of patients during the intravenous (IV) opioid shortage (01/01/18-03/31/18) and a control cohort (01/01/17-03/31/17). Total IV opioids and alternative sedative administration were assessed. Richmond Agitation Sedation Score (RASS) and Clinical Pain Observation Score (CPOT) assessments were also evaluated. The primary outcome was percentage of RASS within goal. Secondary outcomes included duration of mechanical ventilation, hospital/ICU length of stay, and mortality. Results: One hundred patients were included (50 patients per cohort). In the shortage cohort, 23.2% fewer IV opioids were used (40 501.8 vs 52 713.8 oral morphine equivalents [OME]). No statistical differences were found in percentage of patients within goal RASS between the shortage and control (median 63.7% vs 74.8%; P = .094) or CPOT (median 49.7% vs 47.7%; P = .575). More patients received enteral opioids and propofol on day 1 in the shortage cohort when compared to the control (22% vs 4%; P = .007 and 76% vs 56%; P = .035) but there were no differences in benzodiazepine, dexmedetomidine, or antipsychotic use. No differences in mechanical ventilation, hospital/ICU length of stay, or mortality were found. Conclusions: Use of less IV opioids during the injectable opioid shortage did not affect achievement of goal RASS and CPOT scores or increase prescribing of sedative medications such as benzodiazepines in the MICU.

The Path to New Pediatric Vaccines against Pertussis.

Whooping cough, or pertussis, mostly caused by Bordetella pertussis, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent B. pertussis infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches.

Comparison of the Incidence of Nausea and Vomiting in the Administration of Tramadol 100 mg Suppositories with Intravenous Post-Spinal Anesthesia for Lower Extremity Surgery

Pendahuluan : Post operative nausea vomiting (PONV) pasca pemberian tramadol Postoperative nausea vomiting (PONV) after intravenous administration of tramadol has a high incidence rate, so it needs alternative drug administration to overcome this problem. This study aims to compare the incidence of postoperative nausea and vomiting in the intravenous administration of tramadol suppositories. A double-blind analytical experimental study, involving 36 subjects divided into tramadol suppositories and intravenous tramadol post-extremity surgery with spinal anesthesia at Haji Adam Malik Hospital and Network Hospital in 2013. The incidence of PONV in tramadol suppository subjects was much lower than in intravenous tramadol subjects.

Development of vaccine formulations: past, present, and future

The current situation, heavily influenced by the ongoing pandemic, puts vaccines back into the spotlight. However, the conventional and traditional vaccines present disadvantages, particularly related to immunogenicity, stability, and storage of the final product. Often, such products require the maintenance of a “cold chain,” impacting the costs, the availability, and the distribution of vaccines. Here, after a recall of the mode of action of vaccines and the types of vaccines currently available, we analyze the past, present, and future of vaccine formulation. The past focuses on conventional formulations, the present discusses the use of nanoparticles for vaccine delivery and as adjuvants, while the future presents microneedle patches as alternative formulation and administration route. Finally, we compare the advantages and disadvantages of injectable solutions, nanovaccines, and microneedles in terms of efficacy, stability, and patient-friendly design.Graphical abstractDifferent approaches to vaccine formulation development, the conventional vaccine formulations from the past, the current development of lipid nanoparticles as vaccines, and the near future microneedles formulations are discussed in this review.

Cooperative Role of Thrombopoietin and Vascular Endothelial Growth Factor-A in the Progression of Liver Cirrhosis to Hepatocellular Carcinoma.

Primary thrombopoietic mediator thrombopoietin (THPO) is mainly produced by the liver; it may act as a growth factor for hepatic progenitors. Principal angiogenesis inducer vascular endothelial growth factor-A (VEGF-A) is critical for the complex vascular network within the liver architecture. As a cross-regulatory loop between THPO and VEGF-A has been demonstrated in the hematopoietic system, the two growth factors were hypothesized to cooperatively contribute to the progression from liver cirrhosis (LC) to hepatocellular carcinoma (HCC). The mRNA and protein expression levels of THPO, VEGF-A, and their receptors were examined, compared, and correlated in paired cancerous and LC tissues from 26 cirrhosis-related HCC patients, using qRT-PCR and immunohistochemistry. THPO and VEGF-A were alternatively silenced by small interfering RNA (siRNA) in human liver cancer cell lines Huh7 and HepG2. THPO and VEGF-A expressions significantly increased in tumor versus LC tissues. HCC and paired LC cells expressed similar levels of THPO receptor (R), whereas vascular endothelial growth factor receptor (VEGFR) -1 and VEGFR-2 levels were higher in HCC than in corresponding LC tissue samples. A significant linear correlation emerged between THPO and VEGF-A transcripts in HCC and, at the protein level, THPO and THPOR were significantly correlated with VEGF-A in tumor tissues. Both HCC and LC expressed similar levels of gene and protein hypoxia inducible factor (HIF)-1α. Positive cross-regulation occurred with the alternative administration of siRNAs targeting THPO and those targeting VEGF-A in hypoxic liver cancer cell lines. These results suggest THPO and VEGF-A might act as interdependently regulated autocrine and/or paracrine systems for cellular growth in HCC. This might be clinically interesting, since new classes of THPOR agonistic/antagonistic drugs may provide novel therapeutic options to correct the frequent hemostatic abnormality seen in HCC patients.

Application and validation of a coaxial liquid core waveguide fluorescence detector for the permeation analysis of desmopressin acetate

In recent years, the development of peptide drugs and alternative routes of administration, such as buccal and sublingual routes, has become increasingly important to the pharmaceutical industry. Performing experiments under physiologically relevant conditions is still a challenge that has not yet been fully mastered. The requirements associated with these alternative administration routes (e.g. permeation testing for buccal administration) push common analytical detection systems in pharmaceutical technology to their limits, especially with regard to large molecules and peptides. An HPLC-coupled coaxial liquid-core waveguide fluorescence detector has been developed and evaluated within this study to overcome these limits by achieving a more sensitive detection. Desmopressin acetate was selected as the peptide drug with the aim of investigating its permeation behavior during the clinically relevant application period of one hour. Based on the detector system, a complete validation according to the requirements of international guidelines was successfully performed. The results of the validation showed an increase in sensitivity resulting in a limit of detection of 4.7 ng/mL and a lower limit of quantification of 9.5 ng/mL. Moreover, it has been demonstrated that the permeation of desmopressin can be observed in clinically relevant dosages and time periods of up to one hour using this innovative detector system.

The Four Square Step Test and its Use Clinically in Different Populations

This review will summarize and appraise the most recent literature that has been published on the Four Square Step Test (FSST) so that clinicians can make informed decisions about its appropriate use with patients. The FSST is a valid and reliable measure of dynamic balance that has been successfully utilized across age cohorts and in multiple patient populations including those with neurologic diagnoses, musculoskeletal pathologies, and lower limb amputations. Performance on the FSST correlates with the functioning of multiple body structures, processes, and systems and it may be useful in predicting the care needs of older adults. The FSST does have some limitations; however, and in order to address these limitations, alternative administrations have been developed. The initial literature on these variations shows promise in their ability to build on the clinical utility of the traditional FSST. The FSST is quick, easy, and inexpensive to administer. It has robust psychometric properties, and there is a rapidly growing body of literature on its use in diverse circumstances. When using the FSST with specific populations, clinicians should refer to the available literature to determine the appropriateness of the test, how to interpret scores, and the potential utility of alternative administration methods. Future research should continue to explore the utility of these alternative administrations, as well as the use of the FSST in combination with other balance and mobility measures, and the relationship between FSST score and various body structures, functions, and systems.

Development and characterization of nano-emulsions and nano-emulgels for transdermal delivery of statins

ABSTRACT Background Oral administration of statins for the treatment of familial hypercholesterolemia results in poor therapeutic outcomes and patient compliance. An alternative administration route is proposed to circumvent the current limitations. This research is aimed at developing nano-emulsions and nano-emulgels as the ultimate potential delivery systems of statins for administration via the transdermal route. Methods Oil-in-water (o/w) nano-formulations (nano-emulsions and nano-emulgels) containing 2% (w/w) of the selected statin and 8% apricot kernel oil as oil phase were formulated. The nano-formulations were characterized using transmission electron microscopy (TEM), pH, viscosity, droplet size and zeta-potential. Results Nano-emulsions’ and nano-emulgels’ droplet size ranged between 114.23–169.83 nm and 149.83–267.53 nm, respectively. The addition of Carbopol® Ultrez 20 increased the nano-emulsions’ viscosity (3.59–8.38 cP) resulting in the formation of nano-emulgels (viscosity: 1911.00–46,090.00 cP). The entrapment efficiency (90.77–99.55%) confirmed the incorporation of the statins. Membrane release studies indicated that statins were released at higher flux values in nano-emulsions compared to their respective nano-emulgels. Ex vivo (skin diffusion) studies indicated higher median values in the nano-emulgels compared to their nano-emulsion counterparts. Conclusions The results indicate the benefits of nano-emulsions and nano-emulgels as potential alternative delivery systems for the transdermal delivery of statins.

What's New in Allergen Immunotherapy Patents? A Review.

In recent years, allergies are on the rise. The growth of allergies cases has changed the immune system's response to new pathogens. The therapy used to treat these diseases is based on allergen avoidance, pharmacotherapy and allergen-specific immunotherapy. The last one has received a lot of interest in the research field, due to the possibility of leading the patient to a cure. In this sense, new allergen immunotherapy need to be developed or improved to increase safety and efficiency. This review aims to evaluate patents published, from 2015 to July 2020, that have developed allergic immunotherapy treatment and administration routes, as well as new alternatives of vehicles, carriers and delivery systems in this context. The advance of new patents has been mostly seen in China and United States. The oral route is the most used in the development of new allergy treatments. However, due to the challenges that still exist in allergy therapy, association with other pathways is interesting to amplify the possibilities and alternatives of treatment. Thus, other routes of administration for allergen-specific immunotherapy such as topical, sublingual and intranasal have been explored in the research and industrial fields. Nevertheless, it has been observed that few studies are using these alternative administration routes, probably due to the higher cost and lack of investments. The delivery systems are also other tools that can be more explored in the allergen immunotherapy formulations. The effectiveness, safety and acceptance of this therapy depends on the development of new formulations and routes of administration.

A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia

AbstractPreclinical studies with the histone deacetylase (HDAC) inhibitor depsipeptide (FK228) in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have demonstrated that it effectively induces apoptosis at concentrations at which HDAC inhibition occurs. We initiated a minimum effective pharmacologic dose study of depsipeptide, targeting an in vivo dose at which acetylation of histone proteins H3 and H4 increased by 100% or more in vitro. Ten patients with CLL and 10 patients with AML were treated with 13 mg/m2 depsipeptide intravenously days 1, 8, and 15 of therapy. Neither life-threatening toxicities nor cardiac toxicities were noted, although the majority of patients experienced progressive fatigue, nausea, and other constitutional symptoms that prevented repeated dosing. Several patients had evidence of antitumor activity following treatment, but no partial or complete responses were noted by National Cancer Institute criteria. HDAC inhibition and histone acetylation increases of at least 100% were noted, as well as increases in p21 promoter H4 acetylation, p21 protein, and 1D10 antigen expression. We conclude that depsipeptide effectively inhibits HDAC in vivo in patients with CLL and AML, but its use in the current schedule of administration is limited by progressive constitutional symptoms. Future studies with depsipeptide should examine alternative administration schedules.

NURS-11. MARIJUANA, HEMP, AND THE CHILD WITH CANCER: PATIENT, PARENT, AND CLINICIAN EDUCATION

Many pediatric oncology patients report medical marijuana (MMJ) and hemp-based CBD use. Eleven states and Washington, DC have legalized marijuana for recreational use for adults greater than 21. Medical marijuana is legalized in 33 states. Additionally, due to the bipartisan Farm Bill passed in December of 2018, hemp is federally legal. Marijuana has medical legalization in 23 countries worldwide. Clinical trials in adults have examined MMJ for cancer-related symptoms. New research is emerging on MMJ in anticancer therapy, MMJ receptors on tumor cells, and the potential role for MMJ as an immunomodulator. Few pediatric oncology studies have evaluated MMJ. We describe the initial findings of a prospective observational study of MMJ on the quality of life (QOL) in pediatric brain tumor patients. Specific aims included (1) MMJ’s association with symptoms (nausea, anxiety, pain, fatigue, and cognitive problems) and (2) MMJ’s impact on family dynamics. The legality of hemp plus the increasing use of MMJ raises concerns with pharmacological interactions with CBD and the medications routinely administered to children with cancer. Nurses are the frontline for discussions with patients about MMJ and must be aware of the emerging field of MMJ in pediatric cancer. Additionally, nurses can influence patient care protocols and processes for alternative therapy administration enabling an open dialogue between providers, parents, and patients regarding treatments, symptoms, adverse effects, and drug interactions. Education about how to have conversations about important facets to cover and consider is crucial to patient safety and increased quality of life.

Erlotinib entrapped in cholesterol-depleting cyclodextrin nanoparticles shows improved antitumoral efficacy in 3D spheroid tumors of the lung and the liver

Erlotinib (ERL), a tyrosine kinase inhibitor approved for therapeutic use in non-small cell lung cancer is further researched for eventual liver cancer treatment. However, conventional ERL has important bioavailability problems resulting from oral administration, poor solubility and gastrointestinal degradation into inactive metabolites. Alternative administration routes and nanoparticulate drug delivery systems are studied to prevent or reduce these drawbacks. In this study, ERL-loaded CD nanosphere and nanocapsule formulations capable of cholesterol depletion in resistant cancer cells were evaluated for ERL delivery. Drug loading and release profile depended largely on the surface charge of nanoparticles. Antiproliferative activity data obtained from 2D and 3D cell culture models demonstrated that polycationic βCD nanocapsules were the most effective formulation for ERL delivery to lung and liver cancer cells. 3D tumour tumoral penetration studies further revealed that nanocapsule formulations penetrated deeper into the tumour through the multilayered cells. Furthermore, all formulations were able to extract membrane cholesterol from lung and liver cancer cell lines, indicating the induction of apoptosis and overcoming drug resistance. In conclusion, given their tumoral penetration and cell membrane cholesterol depletion abilities, amphiphilic CD nanocapsules emerge as promising alternatives to improve the safety and efficiency of ERL treatment of both liver and lung tumours.

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars.

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a–b and 11a–b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I2/ImH activating system, which provided the desired compounds in high yields (94–96%) by a one-pot procedure. The substantial increase in the lipophilicity of 10a–b and 11a–b is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.

Transbuccal Delivery of Isoniazid: Ex Vivo Permeability and Drug-Surfactant Interaction Studies.

The oral administration of isoniazid (INH) may lead to discontinuation of tuberculosis treatment due to drug-related hepatotoxicity events, and thus, the transbuccal delivery of this drug was investigated, for the first time, as an alternative administration route. Ex vivo permeability assays were performed in Franz-type diffusion chambers, applying INH alone and in combination with sodium dodecyl sulfate (SDS) and sodium taurocholate (ST). After confirming the formation of micelle structures by dynamic light scattering analysis, UV-visible spectroscopy and zeta potential analyses were used to investigate drug-micelle interactions. In zeta potential analyses, no electrostatical interactions were identified for both surfactants in saliva buffer pH6.8. Spectrophotometric analyses, in turn, indicated chemical interactions between INH and SDS in both pH values (2.0 and 6.8) whereas no interaction between the drug and ST was observed. Despite the interaction between SDS and drug, this surfactant increased the buccal transport rate of INH by approximately 11 times when compared with the control. In contrast, ST did not increase the drug permeability. The INH retention in SDS-treated mucosa was significantly higher when compared with the control and an effect on intercellular lipids was suggested. In vivo studies are needed to confirm the high INH absorption found here. Grapical abstract.

Engineering Antiviral Vaccines.

Despite the vital role of vaccines in fighting viral pathogens, effective vaccines are still unavailable for many infectious diseases. The importance of vaccines cannot be overstated during the outbreak of a pandemic, such as the coronavirus disease 2019 (COVID-19) pandemic. The understanding of genomics, structural biology, and innate/adaptive immunity have expanded the toolkits available for current vaccine development. However, sudden outbreaks and the requirement of population-level immunization still pose great challenges in today’s vaccine designs. Well-established vaccine development protocols from previous experiences are in place to guide the pipelines of vaccine development for emerging viral diseases. Nevertheless, vaccine development may follow different paradigms during a pandemic. For example, multiple vaccine candidates must be pushed into clinical trials simultaneously, and manufacturing capability must be scaled up in early stages. Factors from essential features of safety, efficacy, manufacturing, and distributions to administration approaches are taken into consideration based on advances in materials science and engineering technologies. In this review, we present recent advances in vaccine development by focusing on vaccine discovery, formulation, and delivery devices enabled by alternative administration approaches. We hope to shed light on developing better solutions for faster and better vaccine development strategies through the use of biomaterials, biomolecular engineering, nanotechnology, and microfabrication techniques.

Dry Emulsions based on Alpha Cyclodextrin and Vegetable Oils for Buccal Delivery of Lipophilic Drugs

Background: Buccal delivery of drugs can be used as an alternative administration route to conventional oral route avoiding the liver first-pass effect and improving patient compliance. Objective: The goal of this work was to develop dry emulsions for buccal delivery of ketoprofen, used as a lipophilic model drug. The influence of two vegetable oils, olive oil or wheat germ oil, in the presence of α-cyclodextrin and different drying techniques on the dry emulsion properties was evaluated. Methods: Emulsions were prepared by adding olive oil or wheat germ oil to an aqueous solution of α-cyclodextrin and subsequently dried through an oven, freeze-dryer or spray-dryer. Dry emulsions were characterized in terms of yield, encapsulation efficiency, morphology and drug solid-state. In vitro drug release and permeation studies were carried out to evaluate dry emulsion ability to release the drug and to allow its permeation through the esophageal porcine epithelium. Results: The formation of stable and milky emulsion was assured by cyclodextrin ability to interact with oil components obtaining an inclusion complex with amphiphilic property able to act as a surfaceactive agent. The drying process influenced the yield and the encapsulation efficiency, while no significant differences were observed between olive oil and wheat germ oil. Freeze-dried emulsions, selected as the best formulations, resulted in fast release of drug thereby ensuring its permeation across the epithelium. Conclusion: Dry emulsions prepared with a simple and easy method, using natural ingredients and avoiding synthetic surfactants and organic solvents, could be used for buccal delivery of lipophilic drugs.

New Formulation and Evaluation of Camptothecin Encapsulated and/or Dispersed Suppository.

Camptothecin is known for its potent anticancer activity. However, its optimal activity is reduced due to its low solubility and stability in biological media. The aim of the present study is to design and characterize a Camptothecin (CPT) suppository formulation. Rectal suppositories of camptothecin alone, encapsulated with Cyclodextrin (CD) and in the ternary system (CPT encapsulated with cyclodextrin and dispersed in Polyethylene Glycol (PEG) 6000) were prepared using various hydrophobic and hydrophilic polymeric bases as semi-synthetic glyceride (Suppocire® AM Pellets) and Polyethylene Glycols (PEGs) mixtures. Formulations were evaluated by various parameters like weight variation, drug content, hardness and liquefaction time. In vitro release study was performed in USP type I apparatus using phosphate buffer pH 7.2 as dissolution media. Suppositories were within the permissible range of all physical parameters. In vitro drug released from water soluble base (PEG) was greater than that from oil soluble base with ninety percent (90%) of drug dissolution. It was also established that drug release from various formulations was by diffusion mechanism, according to the Higuchi's equation. This new formulation offers a new approach to colorectal cancer treatment by offering an alternative and simple drug administration route.

MEK1/2 Inhibition in Murine Heart and Aorta After Oral Administration of Refametinib Supplemented Drinking Water.

Upregulation of the RAS-RAF-MEK-ERK-MAPK pathway is involved in the development of several human tumors, aortic aneurysms, atherosclerosis, and cardiomyopathy. Refametinib, a highly selective MEK-inhibitor, has already shown antineoplastic activity in phase II trials. Furthermore, it showed potency to attenuate aortic root growth in murine models. Current formulations of this drug however necessitate oral gavage as a delivery method for long-term studies, which is labor-intensive and induces stress and occasional injury, potentially confounding results. Therefore, we developed a novel oral administration method for refametinib. A 2-hydroxypropyl-beta-cyclodextrin (HPBCD) based drinking water preparation of refametinib was formulated, for which a selective, analytical UHPLC-UV method was developed to assess the in-use stability. Next, 16 week old male wild-type C57Bl/6J mice received either a daily dose of 50 or 75 mg/kg/day refametinib or were given regular drinking water during 7 days. In both dosage groups the refametinib plasma levels were measured (n = 10 or 7, respectively). Furthermore, pERK/total ERK protein levels were calculated in the myocardial and aortic tissue of mice receiving a daily dose of 50 mg/kg/day refametinib and untreated mice (n = 4/group). After 7 days no significant degradation of refametinib was observed when dissolved in drinking water provided that drinking bottles were protected from UV/visible light. Furthermore, a dose-dependent increase in refametinib plasma levels was found whereby active plasma levels (> 1.2 µg/mL) were obtained even in the lowest dose-group of 50 mg/kg/day. A significant reduction of pERK/total ERK protein levels compared to untreated mice was observed in aortic and myocardial tissue of mice receiving a daily dose of 50 mg/kg/day refametinib. Importantly, a relatively high mortality rate was noted in the highest dose group (n = 5). This approach provides a valid alternative oral administration method for refametinib with a reduced risk of complications due to animal manipulation and without loss of functionality, which can be implemented in future research regarding the malignant upregulation of the RAS-RAF-MEK-ERK-MAPK pathway. However, care must be taken not to exceed the toxic dose.