AN INVESTIGATION OF EXPERIMENTAL PARAMETERS REQUIRED TO STUDY HYDROCARBON PHASE BEHAVIOR UNDER CONSTANT VOLUME AND CONSTANT COMPOSITION CONDITIONS

Accurate fluid phase behavior evaluation is essential for reservoir engineers to predict the type of reservoir, oil and gas in place, and develop proper production strategies. The change in phase behavior and phase equilibrium are key to understand the reservoir condition and estimate production from a particular formation. In shale reservoirs, hydrocarbon phase behavior in nanopores can be affected by various factors such as pore proximity and pore size distribution. In many shale and tight oil and gas reservoirs, pore sizes are in the ranges of nanometers. Various simulation models are seen in literature attempting to predict phase behavior under confinement but there is no good reference of experimental results for verification. Our research team is trying to conduct phase behavior tests for single, binary, and multi-component hydrocarbon mixtures under confinement to validate and test the various simulation models. Since that’s not an easy endeavor, each of us in the research team has taken on one of the challenging tasks to accomplish the goal. My particular goal is to examine the feasibility of a new experimental procedure for detecting the edge of the phase envelope. The new experimental approach for detecting the phase envelope was examined through numerical simulation of binary hydrocarbon mixtures in bulk since these bulk simulation numbers have been verified experimentally in the past. The binary hydrocarbon mixtures we examined were Ethane with Propane, Pentane, Heptane and Hexane with 50-50 mole percentage. As per the experimental feasibility in the laboratory and lower temperature and pressure ranges available, various compositions of Ethane-Pentane system were studied in order to design the experimental parameters. The results of this study will be used by the rest of the members in the research team to conduct the experiments as it provided them with the most suitable system to explore in the laboratory

Topical Clear Aqueous Nanomicellar Formulation for Anterior and Posterior Ocular Drug Delivery

VitaTitle from PDF of title page, viewed on August 31, 2016Dissertation advisor: Ashim K. MitraVitaIncludes bibliographical references (pages 329-352)Thesis (Ph.D.)--School of Pharmacy and Department of Chemistry. University of Missouri--Kansas City, 2015The objective of this study was to develop a clear, aqueous drug loaded nanomicellar formulation (NMF) for the back-of-the-eye delivery. Hydrophobic drugs such as cyclosporine, resolvin analog (RX-10045), dexamethasone, rapamycin were entrapped in the core of polymeric micelles and solubilized. Polymeric amphiphilic molecules (e.g., hydrogenated castor oil – 40 (HCO-40) and Vit. E TPGS) are known to generate nanomicellar constructs with hydrophobic core and hydrophilic corona. However, constructs prepared from a single polymer are unstable and easily fall apart at high temperature. Inclusion of a second polymer such as Oc-40 improves stability and prevents nanomicellar destabilization. Such stable nanomicellar constructs can encapsulate hydrophobic drugs in their lipophilic core while the hydrophilic corona helps solubility in aqueous solution. We screened resolvin for efflux pumps and prepared resolvin analog nanomicelles. Studies showed that NMFs were tolerable and delivered high drug concentrations to back-of-the-eye tissues with topical eye drop application to rabbits. Negligible drug levels were quantified in systemic circulation. These nanomicellar constructs efficiently utilize their hydrophilic corona and evade the wash-out into the systemic circulation from both the conjunctival and choroidal blood vessels and lymphatics, thus overcoming the dynamic barrier. Moreover, this pathway might overcome the major drawback associated with steroid therapy (glaucoma and cataract), since a trans-scleral route of absorption is accessed. In summary, for the first time we identified that resolvin analog was substrate/inhibitor for BCRP and MRP but not P-gp. Moreover, resolvin analog was identified as a strong inhibitor of influx transporter (OCT-1). Clear, aqueous NMF encapsulating hydrophobic drugs were successfully developed. Ocular bioavailability and pharmacokinetic studies demonstrated a very high drug levels in retina-choroid (place of drug action) with a negligible drug partitioning into lens and vitreous humor. These results suggest that drug and/or NMFs cannot reach back-of-the-eye tissues following corneal pathway. Alternatively, ~12 nm - 20 nm nanomicelles efficiently permeate through 20 nm to 80 nm scleral pores and reach back-of-the-eye tissues (retina-choroid) following conjunctival-scleral pathway. In the lipoidal posterior ocular tissues, these nano-constructs may release the cargo into Bruch’s membrane/retina-choroid generating high drug levels.Introduction -- Literature review -- Topical aqueous clear cyclosporine nanomicellar formulation: optimization, in vivo ocular toxicity evaluation and pharmacokinetic study -- Topical aqueous clear resolvin E1 analog (RX-10045) nanomicellar formulation -- Part A: interaction studies of resolvin E1 analog with efflux transporters -- Part B. formulation optimization and in vivo evaluation -- Topical aqueous clear dexamethasone nanomicellar formulation: optimization and in vivo tissue distribution -- Topical aqueous clear rapamycin (sirolimus) nanomicellar formulation: develop,emt and in vivo issue distribution -- Summary and recommendations -- Appendi

Topology and FEA modeling and optimization of a patient-specific zygoma implant

Additive manufacturing has proven to be a very beneficial production technology in the medical and healthcare industries. While existing for over four decades, recent work has seen great improvements in the quality of products; particularly in medical devices such as implants. Improved customization reduced operating time and increased cost-effectiveness associated with Metal AM for these products offers a new value proposition. This paper investigates and evaluates modelling methods for the zygoma bone (human jawbone) and explores the most suitable material and optimum design for this critical biomedical implant. This paper proposes an innovative and efficient pre-process methodology that includes modelling, design validation, topological optimization, and numerical analysis. The method includes the generation of the model using reverse engineering of CT scan data and a topology optimization technique which makes the implant lightweight without causing excessive stress concentration. Static structural Finite Element Analysis was conducted to test three different biocompatible materials (Ti6Al4V, stainless steel 316L and CoCr alloys) which are commonly available for metal additive manufacturing. The stresses and conditions in the analysis were that of the human mastication process and all the implant design were tested with the three material types. The Taguchi method was used to determine the optimum design which was found to result in the highest mass reduction of 25% with Ti6Al4V as the implant material

Ultrafast laser-induced surface structuring of anti-fouling steel surfaces for biomedical applications

Metallic surfaces are increasingly used in medical applications due to their favorable material properties such as high strength and biocompatibility. In medical applications antifouling properties are an important requirement especially for implants and medical devices which come into contact with different types of fluid streams. These should be anti-fouling in order to prevent contamination and corrosion. Laser processing methods such as ultrafast laser processing is a one-step and scalable process for surface texturing. This process can be used to produce well-defined surface nano- and microscale superficial textures such as Laser-induced Periodic Surface Structures (LIPSS) which can enhance the anti-fouling capability of the surface. In this study, micro and nano scaled LIPSS structures are manufactured on a biocompatible grade stainless steel 316L substrate using an ultrafast (<370 fs) and low power (<4 W) laser system. With an aim to optimize the anti-fouling properties, laser process parameters such as pulse energy, pulse repetition rate and beam scanning speed were varied to produce microstructures on the stainless-steel surface of varying dimensions. Surface roughness was analyzed using a laser surface profilometer and changes in the hydrophobicity were examined using water contact angle goniometry

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease