This study is a first step toward the development of a vaccine cream that will be applied to the skin in the same way as cosmetic formulations. Skin may be a potent immunological induction site since it acts as an immune barrier by its immunocompetent cells. Vaccines that target the skin only require delivery through the outermost skin layer (stratum corneum), which is an effective but fragile barrier that can be disrupted by hydration. Therefore, several studies have already shown strong systemic and mucosal immune responses following topical application. Transcutaneous immunization has the potential to make vaccine administration easier and cheaper, while maintaining efficiency and safety, which would facilitate the implementation of worldwide mass vaccination campaigns and provide the means for a fast response to terrorist bio-attacks Our main goal was to provide a novel stimulus-responsive water-in-oil-in-water (W1/O/W2) double-emulsion system for vaccine administration to the skin. By use of fluorescence capillary video-microscopy we prepared and monitored individual W1/O/W2 double-emulsion globules subjected to pH and temperature stimuli in order to control the release of model drugs (FSS) and proteins (FITC-BSA), respectively: (1) We proposed a method to fine-tune release of small drugs from double emulsions. Complexation of the active species with oppositely-charged nanohydrogels---confined within the emulsion globules---prevented leakage until presence of acid disrupted such complex and activated release. (2) The delivery of proteins requires an external stimulus that breaks the emulsion globules. We demonstrated that this can be achieved by temperature swings that cause the oil phase to freeze and thaw. Finally, a model W1/O/W2 double emulsion was developed in bulk which remained stable during months of storage at low temperature and efficiently released the encapsulated protein (FITC-13SA) upon temperature increase According to the double-carrier concept introduced here, the proposed W1/O/W2 double emulsion may be used in combination with cationic nanohydrogels. Thus, we suggest that the double emulsion would protect the vaccine during storage and facilitate topical application, while the hydrogel nanoparticles enhance its delivery to the antigen-presenting cells---located below the stratum corneum---so that an immune response is generated / acase@tulane.edu

No description available.

No description available.

Thesis (Ph.D.)--Brown University, 2008. / Vita. Advisor: Kate L. Lapane. Includes bibliographical references (leaves 52-57).

The use of herbal remedies (HR) as complementary and alternative medicines (CAM) appears to be popular despite the limited evidence of their safety and efficacy. The overall purposes of this investigation were to (1) investigate the relationship between regular use of HR and self-reported health status, (2) evaluate this relationship when the HR use was concomitant with pharmaceutical use, and (3) describe consumer beliefs, behaviors, and characteristics related to HR use. A national random-digit dialed telephone survey of 1,500 adult English- and Spanish-speaking Americans was conducted. The survey yielded a response rate of 40.4%. The prevalences of HR use and HR-pharmaceutical concomitant use were 17.1% and 7.9%, respectively. Multivariate modeling indicated that HR use was not associated with health status but was independently associated with race/ethnicity ("other" compared with White adjusted OR = 0.38, 95% CI 0.16-0.85), educational attainment (greater than high school diploma/GED compared with a high school diploma/GED or less adjusted OR = 2.05, 95% CI 1.47-2.87), and urbanicity (Metropolitan Statistical Area- [MSA]-4 compared with MSA-5 adjusted OR = 2.14, 95% CI 1.05-4.34). Among HR users, HR-pharmaceutical concomitant use was independently associated with health status (MCS-12 score adjusted OR = 0.95, 95% CI 0.92-0.99; PCS-12 score adjusted OR = 0.96, 95% CI 0.93-0.99), race/ethnicity (non-White compared with White adjusted OR = 0.26, 95% CI 0.11-0.62), and age (adjusted OR = 1.02, 95% CI 1.01-1.04). Over 45% of HR users reported that they were motivated to use HR for health maintenance. In contrast, HR non-users reported most commonly that the motive to not use HR was because they did not have any health problems that required their use (43.6%). Adult Americans were estimated to have spent between 7.9 and 15.7 billion per year out-of-pocket on HR. Respondents agreed that the government should become more involved in regulating HR safety and efficacy (p < 0.005). In conclusion, this investigation provided evidence that HR and HR-pharmaceutical concomitant use were prevalent across a variety of sociodemographic groups. Furthermore, the evidence indicated that consumers were willing to spend sizeable amounts out-of-pocket for largely unproven preventive agents/therapies, suggesting that the demand for these products would continue.

The purpose of this study was to develop and validate an evaluation instrument that would provide information to sites and schools about the costs and consequences of participating in a pharmacy clerkship program. The evaluation instrument for estimating the learning opportunities at the sites was based on Kolb's theory of experience as a source for learning and development and Bandura's social cognitive theory of thought and action. The evaluation instrument for estimating impact of student training on practice sites was based on the Nonemployee and Employee Models of the student-preceptor relationship and was adapted from an earlier study. Instrument development was an iterative process involving theoretical and empirical components resulting in algorithms, guidelines, and worksheets. Student activities were the unit of analysis for all instruments. Learning opportunity was characterized by level of learning cycle completeness, ranging from no opportunity to completion of all four steps. Student activities were defined by characteristics that were under the control of the site or school and independent of the individual student, thereby removing confounding factors in the estimation process. The impact sustained by a practice site and the student learning opportunities present at the site could be estimated and compared to negotiate a placement that would minimize potential negative impact and maximize the learning opportunities for the clerkship student.

The primary focus of this research is to develop an in vitro method that uses an appropriate formulation:blood ratio and contact time to evaluate the degree of hemolysis occurring after an intravenous injection. The effects of both the formulation composition and the formulation:blood contact time on hemolysis are given in Chapters I-IV. Since hemolysis is shown to increase as either the formulation:blood ratio and/or the contact time increases for various pharmaceutical vehicles, a small formulation:blood ratio and short contact time must be selected to determine the degree of hemolysis occurring as the formulation is rapidly diluted by the blood after an intravenous injection. Using a formulation:blood ratio of 0.1 and a contact time of 1 second, a dynamic method has been developed to evaluate intravascular hemolysis. The ability of this method to accurately evaluate hemolysis occurring after an injection is determined by comparing hemolysis data generated with this dynamic method to in vivo hemolysis data obtained from the literature. The results of this comparison are given in chapter V. The in vitro hemolysis data are shown to be in agreement with in vivo hemolysis data.

The EQ-5D is a brief, multi-attribute, preference-based health status measure. This dissertation describes the development of a statistical model for estimating U.S. population-based preference weights for the EQ-5D health states. A multistage probability sample was selected from the adult U.S. population. Using the time trade-off (TTO) method, each respondent valued 13 of the 243 health states described by the EQ-5D. The valuations were linearly transformed to lie on the interval [-1, 1]. Numerous model specifications were investigated, and a modified split-sample approach was used to evaluate the predictive accuracy of the models. All statistical analyses took into account the clustering and disproportionate selection probabilities inherent in our sampling design. The best model proved to be one based on a conceptual notion of the effect of movements away from perfect health. This model, which we have named D1, included ordinal terms to capture the effect of departures from perfect health as well as interaction effects due to increasing health problems. Relative to other models tested, a random effects specification of the D1 model provided a good fit for the observed TTO data. This model yielded an overall R² of 0.38, a mean absolute error of 0.02, and a correlation between mean observed and predicted valuations of 0.99. We also examined differences in health state valuations among the three major racial/ethnic groups in the U.S., i.e., Hispanics, non-Hispanic blacks, and others. In general, non-Hispanic blacks valued health states more highly than Hispanics or non-Hispanic non-blacks. Non-Hispanic blacks appeared to perceive extreme health problems to be associated with less disutility than did members of the other racial/ethnic groups. Differences in valuations did not appear to be related to differences between groups in education, income, or self-reported chronic conditions. The D1 model predicts the values for observed health states with a high degree of accuracy. This model's predictions provide a set of EQ-5D preference weights specifically developed for use in the U.S. population. Within the U.S. population, there exist differences among the major racial/ethnic groups in the perceived desirability of the EQ-5D health states. These differences cannot be readily explained by socioeconomic disparities.

Various modified methods have been proposed in response to criticisms regarding the practical applicability of allometric scaling, which is one of the most widely used approaches in predicting human drug clearance based on data from animal species. The major problems encountered among allometric methods in predicting human drug clearance are addressed in this dissertation. In chapter 2, a large data set for allometric scaling (n = 138) was collected from the literature and was categorized according to the following criteria: oral or systemic clearance; elimination routes; protein or non-protein chemicals; low, intermediate, or high metabolic clearance. Some significant observations have been made regarding the applicability of allometric scaling according to the pharmacokinetic and physical-chemical properties of the drugs examined. Of special note, several potential rules were developed for when one could expect large vertical allometry. In chapter 3, a new model for predicting human clearance was developed. The new model was shown to provide better predictability than any other current approach. In particular, the new model for the first time predicts the occurrence of large vertical allometry noted in humans. In chapter 4, a general equation was derived, which directly describes the mathematical relationship between predicted pharmacokinetic (PK) parameters in humans and the body weights of animals and the values of their corresponding measured PK parameters. This relationship clearly illustrates the species or body weight-dependency of the prediction performance by allometric scaling. Finally, real data from the literature demonstrated the species-dependency predicted from the equation. In chapter 5, the functionality of the correction factors, maximum life-span potential (MLP) and brain weight (BrW) in allometry is mathematically described for the first time. It was found that corrections by MLP or BrW are equivalent to a multiplication of certain constants by the predicted values in humans from simple allometry and has nothing to do with any measured values of PK parameters in any animal species. The role of correction factors (MLP and BrW) or "rule of exponents" in species scaling was evaluated.

A self-administered, mail questionnaire was used to assess the current state of hospital drug-use evaluation (DUE) programs within short-term, general U.S. hospitals. During February-March 1992, two mailings were sent to pharmacy directors at 491 randomly selected institutions. A net response rate of 66.6% (327/491) was achieved. The level of pharmacist participation in DUE program activities was found to be very high and to have a significant, positive correlation with the rated effectiveness of current DUE programs and the rated importance of pharmacist participation in DUE program activities. Pharmacists were members on 97.9% of responders' DUE (sub)committees, while 65.5% of pharmacist members held voting privileges. Pharmacists devoted an average of 11.27 hours per week to DUE-related tasks. Wide variation was demonstrated in rationale used to select DUE study drugs, interventions employed, use of DUE study results, and methods selected to evaluate DUE program effectiveness.