• Technologies For Skin Delivery Of Hydrophilic Molecules And Macromolecules

      SONG, YANG
      ABSTRACT TECHNOLOGIES FOR SKIN DELIVERY OF HYDROPHILIC MOLECULES AND MACROMOLECULES Under the direction of Dr. Ajay.K.Banga, Professor and Chair of the Department of Pharmaceutical Sciences, Mercer University Transdermal delivery can bypass first pass metabolism, increase the bioavailability of drug and usually it is a non-invasive administration method and shows better patient compliance. While the transdermal delivery has some limitations, which hinders its wide application. Skin only allow the passage of drug molecules, which should ideally be moderately lipophilic (log P between 1-3) with a molecular weight <500 Da. Stratum corneum as a lipid barrier, it blocks the delivery of drug through the skin, especially for large and hydrophilic molecules such as peptide or protein. As a result, different strategies or devices have been developed to compromise the stratum corneum and enhance the drug permeation. In our studies, we investigated the delivery of hydrophilic small molecules and large molecules in/through the skin by optimizing the formulation, developing drug delivery systems or using physical enhancement techniques, such as maltose microneedle and ablative laser. The first aim was to optimize a gel formulation of cimetidine to maximize its transdermal delivery across microporated skin. Specifically, the effect of extent of ionization in formulation on permeation of cimetidine across microporated skin was studied. Results suggest that 0.8% w/w pH 5 gel showed highest permeation through microchannels compared with other formulations. In order to assess the skin irritation potential of cimetidine carbopol gel, skin irritation test had been performed using EpidermTM-200-SIT kit and results showed 0.8% pH 5 gel is not irritate to the skin. In the second aim, we investigated the feasibility of transdermal delivery of human growth hormone (hGH) through laser-microporated dermatomed porcine ear skin. Laser-assisted microporation creates microchannels in the skin that result in the enhancement of drug delivery. The effect of fluence of laser (34.1, 45.4 and 68.1 J/cm2) and micropores density (5%, 10% and 15%) on the permeation of hGH through laser-treated skin was studied. Permeation study results showed after 48 h, application of fluence of 68.1 J/cm2 laser resulted in significantly higher permeation of drug (90.94±3.93 µg/cm2) than that from 34.1 J/cm2 group (53.13±1.75 µg/cm2, p<0.05), but not as compared to the 45.4 J/cm2 group (p>0.05). With the increase in density of micropores from 5% to 15%, permeation of hGH increased significantly from 7.1±2.63 µg/cm2 to 95.89±13.43 µg/cm2 after 48 h study. In the third aim, we developed a controlled release system using Eudragit® RS100 and polyvinyl alcohol polymer. This microsponge based drug delivery technique can incorporate both hydrophilic and hydrophobic molecules and drug release follows the mechanism of process of diffusion. Salicylic acid microsponge was prepared by quasi emulsion solvent diffusion method and dispersed into 2.0 % carbopol gel. The structure of microsponge was checked under bright microscopy and scanning electron microscopy. Characterization studies of salicylic acid microsponge including loading efficiency, production yield and entrapment efficiency was performed. We tested the drug release profiles and permeation performance from the formulation with/without microsponge using dissolution tester and vertical Franz cell. Release study and permeation study results showed incorporation of salicylic acid in the microsponge did slow down the release rate from the formulation. Microsponge system plays a very important role in controlling the release as well as the permeation of salicylic acid topically. Microsponge was proved to be a potential carrier for salicylic acid in topical acne therapy to prolong drug release, minimize skin irritation and side effects. In the fourth aim, we evaluated the deactivation efficiency of a drug disposal pouch containing granular activated carbon. This activated carbon based drug deactivation system offers a unique disposal method. The deactivation study and desorption study were carried out using diazepam, lorazepam tablets and suboxone® sublingual film. Deactivation study results showed this drug disposal pouch successfully deactivated the drug within 28 days; more than 99% of drug had been adsorbed by the activated carbon. In the desorption study, only about 1% of drug leached out from the activated carbon when it exposed to the large volume of water and organic solvent. This activated carbon based drug deactivation system may provide a convenient way for the patients to dispose their unused medications.
    • TECHNOLOGIES TO ENHANCE AND MODIFY DELIVERY OF SMALL MOLECULES INTO AND ACROSS THE SKIN

      Junaid, Mohammad Shajid Ashraf; College of Pharmacy
      Skin, being the most easily accessible route for drug delivery, provides an appealing alternative to the commonly utilized routes. Transdermal drug delivery has multiple benefits including bypassing first-pass metabolism and reduced fluctuations in plasma drug concentrations. However, for passive permeation of a drug molecule through the transdermal route, the molecule should ideally have a molecular weight of < 500 Da, moderate lipophilicity (log P 1-3), and a melting point of < 250 ºC. To achieve the therapeutic plasma concentration for a drug lacking these properties, several chemical and physical enhancement techniques can be implemented. Transcutol, oleic acid, and isopropyl myristate are examples of commonly used chemical penetration enhancers that have been studied in this research. Furthermore, we investigated physical enhancement techniques such as iontophoresis and microneedles to facilitate transdermal delivery. Conversely, microsponges were used to retard the delivery of drug into and across the skin by limiting the amount of drug available for absorption at a given time. In one of the aims, we have explored the effect of chemical penetration enhancers and microsponges on the delivery of a chemical warfare antidote: 4-phenyl butyric acid (4-PBA). We aimed to explore techniques that can modify the delivery of 4-PBA, so that a suitable formulation could be prepared to meet the exact drug delivery profile required to treat any given complication arising from arsenical chemical warfare. Dose titration is important in the case of baclofen (GABAb agonist) treatment since the effective dose varies depending on the individual and disease condition. Maltose microneedles and iontophoresis were investigated to deliver baclofen to reach a therapeutically relevant plasma concentration. Microneedles were observed to be the most promising method in delivering baclofen. Cannabidiol (CBD) is a non-psychoactive component of cannabis extract. CBD is used in the treatment of myriad skin disorders, including atopic dermatitis and psoriasis. Hence, there is a need for topical formulation development for the delivery of CBD. Semisolid preparations such as cream and emulgel of CBD were prepared and evaluated for percutaneous delivery of cannabidiol. Additionally, the effect of drug concentration, chemical penetration enhancers, and essential oils on drug delivery was explored in this study.
    • Testing The Effect Of A Resident-focused Hand Hygiene Intervention In A Long-term Care Facility: A Mixed Methods Feasibility Study

      Morales, Kathleen A
      In the United States of America (U.S.) approximately 3 million people in all healthcare settings develop healthcare-associated infections annually (Centers for Disease Control [CDC], 2016; Office of Disease Prevention and Health Promotion [ODHP], 2013). Hand hygiene is the most effective measure to prevent healthcare-associated infections, making it a clear strategy to prevent healthcare-associated infections. While there is a wealth of evidence regarding the efficacy of healthcare provider’s hand hygiene, there is a paucity of research available related to the role of residents’ hand hygiene in preventing healthcare-associated infections. Many long-term care facilities lack specialized infection control staff, creating a challenge for infection control and surveillance in this setting. The purpose of this study was to test the feasibility and acceptability of a resident-focused hand hygiene intervention within a long-term care facility, using a mixed methods design. The study followed an exploratory sequential design. The strands were implemented sequentially, starting with qualitative data collection and analysis. The qualitative strand began with direct observation which is the gold standard to monitor hand hygiene adherence. Next, interviews of six residents and six staff members were completed using a semi-structured interview guide. Qualitative findings informed the second strand, which had a quantitative emphasis. The quantitative strand of the study was a quasi-experimental clinical trial (n=12 residents), implemented with a pre-test/post-test design with one experimental group and no control group. Participants in the quantitative strand were recruited and completed pre-intervention questionnaires on day one. Pre-observation occurred on day two with the educational intervention on day three. Post-intervention observation and questionnaires were completed on day four, which was 24 hours post- intervention and 72 hours after the pre-intervention data collection. The educational intervention revealed clinically important and positive changes in hand hygiene related health beliefs. While findings suggested the educational intervention improved respiratory hygiene, meal-related hand hygiene demonstrated only a minimal increase. Qualitative data revealed hand hygiene may be less amenable to change because of meal-related hand hygiene habits formed in childhood. A resident-focused hand hygiene intervention actively promotes self-efficacy rather than passive reliance on healthcare staff to assure clean hands during meals. Findings from both the quantitative and qualitative strands provide key information for future piloting of a resident-focused hand hygiene intervention on a larger scale.
    • The COVID-19 Pandemic And The Impact Of Social And Cultural Courses on Ethnocultural Empathy: Cultivating Comfortability, A Program Evaluation

      Paige, Lynn; College of Professional Advancement
      The current study’s findings explored and defined graduate students’ perceptions of the COVID-19 pandemic and the need for multicultural awareness, ethnocultural empathy, (a component of multicultural competency), and comfortability in the learning environment. The program evaluation’s aim is to report the impact of the learning outcomes of pre-designed social and cultural courses that are required in CACERP counseling programs and COAMFTE family therapy programs. As a program evaluation, the study research design was an embedded mixed- methodology that allowed for an analysis of both qualitative and quantitative inquiry. Therefore, a thematic analysis reported themes of multicultural awareness and empathic expressions among graduate students currently enrolled in a counseling program. The overall statistical analysis revealed a significant negative relationship between the number of credits for graduate students currently enrolled in a counseling program, and the level of ethnocultural empathy r= -.533*, p<05. There was a significant positive correlation between the level of comfortability in learning and the level of ethnocultural empathy r =. 05, p<01. A discussion on the areas of success, the study limitations, and implications for future research is included to provide insight of the presented program evaluation. Keywords: multicultural competency, ethnocultural empathy, comfortability, program evaluation, COVID-19 pandemic
    • The Effect Of Dietary Texture On The Composition Of The Murine Dental Microbiome

      Sedghi, Lea Maryam
      Dental plaque exists as a highly complex biofilm community that is known to lead to various states of dental disease. The pathogenicity of the dental biofilm is directly related to the species residing within the biofilm. While some oral biofilm communities are associated with states of oral health, others are interchangeable with states of dental disease and oral pathology. The microbial community population of the oral cavity is heavily influenced by host diet composition. Diet composition contributes to the establishment of differing microbial communities in terms of relative species abundance and diversity. Some diets are associated with oral bacteria related to a healthy oral environment while others show association with microbes that are related to states of dental disease. Many studies have focused on the significance of dietary carbohydrate content on dental disease. However, the effect of dietary texture on dental disease has been comparatively overlooked. This study utilizes 16S rRNA analysis to better understand the influence of diet texture on oral microbial populations among the dental enamel surface in terms of microbial diversity and abundance. Four diet groups—1) Base (Control), 2) Base+Fiber, 3) Base+Sugar, and 4) Base+Fiber+Sugar—are used to determine if dietary texture as well as carbohydrate content affects changes within the oral microbiome to potentially influence dental disease. This study ultimately seeks to offer insight into whether the loss of dietary texture in the Western diet has acted as a stimulus towards increased incidence of dental disease over time. We found that dietary fiber, and not sugar, had a significant effect on dental microbiome alpha and beta diversity at the genus level. Additionally, beta diversity was significantly affected at the phylum level. Consistent with this finding fiber, and not sugar, also explained significant changes in microbial taxonomic abundance at the genus level. These changes were microbe-specific for each dietary group. A general finding was that fiber had a stronger influence on microbial diversity and abundance than did sugar. The only significant effects sugar demonstrated in this experiment were in its interaction with dietary fiber. Further analysis using metagenomic shotgun sequencing should be utilized to better understand the metabolic impact of the changes observed in this preliminary study.
    • The Effect Of Unilaterally Added Mass To The Legs On Able-bodied Gait: Implications On Heavy Prosthesis Design

      Gracyalny, Justin Thomas
      ABSTRACT JUSTIN THOMAS GRACYALNY THE EFFECT OF UNILATERALLY ADDED MASS TO THE LEGS ON ABLE-BODIED GAIT: IMPLICATIONS ON HEAVY PROSTHESIS DESIGN (Under the direction of Dr. Ha Van Vo, Ph.D., MD, DPM) INTRODUCTION: General consensus is that lighter prostheses designs reduce gait deviations and improve energy efficiency; however, these studies have not been able to provide conclusive evidence on the overall effects of different mass distributions, particularly when heavier protheses are involved. METHODOLOGY: Several components of gait mechanics including sagittal and frontal plane joint kinematics, ground reaction forces (GRFs), and relative hamstring energy expenditure (RHEE) were evaluated in able-bodied subjects with unilaterally added mass to the legs simulating a best-case scenario for heavy transtibial and transfemoral prosthesis wearers. Five- and ten-pound masses were added unilaterally to the shank and/or thigh of 10 below-knee (i.e., calf-only) subjects (Baseline, 5lb, and 10lb groups) and 11 above-knee (i.e., calf and thigh) subjects (Baseline, 5lb/5lb and 5lb/10lb groups). RESULTS: Significant differences between weight conditions (p<0.05) were found in self-selected walking speed, cadence, swing time, and stance time. Significant decreases in knee flexion during mid-swing and hip flexion during terminal swing and increases in hip extension during pre-swing were observed with increasing weight. Trunk flexion was found to increase throughout the gait cycle while decreased contralateral trunk lean was found during swing phase of the weighted limb. Relative locations of maximum and minimum joint angles were less affected, and differences were generally not statistically significant. Weighted limb GRF curves generally showed decreased maximum heel strike and toe-off forces with a less defined mid-stance. RHEE was found to increase with heavier loads and was found to increase more with distal loading. DISCUSSION: Findings agree with previous studies regarding the recommendation to avoid distal loading unless other patient benefits are gained. Findings also support idea of kinematically invariant adaptions to gait for mass perturbations. Results suggest increased muscle activity in the lumbar spine with increasing weight with potential links to lower back. Further investigation into this linkage is suggested for future studies. Finally, findings suggest additional unilateral mass plays a significant role on gait and should be avoided when possible. CONCLUSION: This study shows that unilaterally added mass plays a significant role on able-bodied gait mechanics and can be used to support and provide insight for future prosthesis design.
    • The Effectiveness Of Project-based Learning On Mathematics Proficiency With African American Students / By Justina S. Jenkins.

      Jenkins, Justina S
      This sequential exploratory mixed methods study addressed the problem of low academic achievement in mathematics, specifically for African American middle school students who historically score below proficient levels on standardized mathematics assessments. The purpose was to investigate the effectiveness of the Project-Based Learning (PBL) approach on African American students’ academic achievement, and to determine what factors, if any, impact African American students’ motivation during PBL mathematics. Eight sixth-grade students from a private school in the southeastern United States, identified as performing below proficient level in mathematics, participated in this study. Data collection included two focus group interviews, a six-week PBL mathematics unit, classroom observations, and a pre-and post-benchmark assessment. The quantitative results indicated that on average, the students performing below proficient level significantly improved their performance from the pre-test to the post-test. However, their scores were significantly lower than the students who historically performed at math proficient levels, and the PBL unit did little to close the achievement gap. The qualitative data suggest three factors, student perceived level of rigor of the mathematics assignments, the nature of the peer-to-peer interactions, and the presence of classroom-based student activities that the students perceived to be fun and valuable, impact the students’ motivation in PBL. Recommendations for future research include studies of long term impacts on mathematics academic achievement and motivation when students are immersed in PBL over longer periods of time and studies comparing students’ mathematics scores on the SAT or ACT that completed PBL instruction opposed to more traditional methods.
    • The Effects Of Immediate Elaborative Feedback Using Student Response Systems On The Mathematics Achievement Of Fifth-grade Students

      Byrd, Liinda Ann
      Mathematics is one of the core subjects for students. In 2017, the National Center for Education Statistics shared results of the most recent tests in mathematics. Although students have increased in their proficiency since 2000, the 2017 results indicated that the scores of students in the United States continue to be lower in mathematics than the scores of students in other countries, especially students in grades fourth and eighth. Thus, educators need to work on implementing strategies to assist students in increasing their math skills. This quasi-experimental study with pretest and posttest with control group design investigated the effects of elaborative feedback and self-regulation strategy instruction on the mathematics achievement of fifth-grade students. The study’s theoretical framework consisted of distributed cognition and self-regulation. The participants were 26 fifth-grade students from a private Christian school in the southeastern United States. The researcher collected data for 12 weeks. The researcher analyzed data using ANCOVA and independent samples t-tests. The results of the tests showed no significant difference between the experimental and control groups on the STAR Math test and the Self-Regulation Questionnaire. The control group scored slightly higher on the posttest than the experimental group scored. Although the results did not yield a statistically significant difference, educators can recognize the importance of utilizing various strategies to assist students in constructing knowledge in mathematics. Additionally, when educators teach students self-regulation skills and how to collaborate using distributed cognition, they can help students understand the significance of their voices in the learning process. Thus, future research should involve the connection of self-regulation and distributed cognition in the early grades.