No description available.

Recently, there has been an explosion of interest in developing biopharmaceutical therapeutics for the treatment of life altering conditions. The main issue with the utilization of biopharmaceutical therapeutics is the mode of administration. The Oral Ghost Drug Delivery (OGDD) device could potentially enable the administration of these peptide therapeutics via the oral route and significantly extend the application of these advanced therapeutic compounds.

Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within this thesis is the possibility of further developing transdermal drug delivery for chronic pain treatment using an Electro-Modulated Hydrogel- Microneedle array (EMHM) prototype device for the delivery of analgesic medication

No description available.

Drug delivery to the brain has challenged medical professionals for several decades, with 98% of small molecules and 100% of large molecules unable to cross the blood brain barrier (BBB). Biocompatible, biodegradable polymers have been extensively researched for the oral delivery of therapeutic agents, but to date has not been successfully manipulated for the formulation of an implantable device. We have therefore utilised such polymers for the formulation and design of an implantable nanoenabled multipolymeric drug delivery device (NMDDD) for the management of AIDS Dementia Complex (ADC). ADC is a central nervous system (CNS) complication of HIV, associated with a host of debilitating cognitive, motor and behavioural symptoms. ADC remains a serious manifestation of HIV/AIDS in both developing and developed countries, affecting both adults and children, with death expected within 6 months of initial diagnosis. Zidovudine (AZT), the current gold standard for the management of ADC, has demonstrated the best penetration into the CNS. It is capable of reducing viral replication in the CNS and managing neurological abnormalities associated with ADC, with clinical efficacy evidenced by the decline in morbidity and mortality of patients treated with this drug. Nanotechnology, an interdisciplinary field of research, involving the manipulation of matter on a submicron level, is receiving emerging interest for the formulation of novel drug delivery systems. As they can potentially be manipulated to react in a bioresponsive manner, nanopharmaceuticals have received much attention for site-specific drug delivery and were therefore employed in the formulation of an implantable NMDDD, with AZT employed as the model drug, for the management of ADC. Nanoparticles were prepared by means of an approach utilising controlled gelation of alginate, employing cationic crosslinking of the anionic alginate to precipitate nanoparticles. A 3-factor Box-Behnken statistical design was employed for the optimisation of nanoparticle and multipolymeric scaffold formulations. Nanoparticles measuring 68.04nm (SD<0.0002) in size with a zeta potential of -13.4mV (SD<0.0005) were formulated. Nanoparticles presented with a mean dissolution time (MDT) of 46.046 hours 30 days post exposure to phosphate buffered saline (PBS), pH 7.4. In an attempt to further retard drug release and to formulate a device for implantation in the frontal lobe of the brain, nanoparticles were dispersed within a robust multipolymeric matrix. Matrix erosion was calculated at 28%w/w (SD<0.001) for multipolymeric scaffold and a matrix resilience of 4.451%w/w (SD<0.007) was observed 30 days post exposure to PBS, indicating slow degradation of the NMDDD. MDT was reduced to 12.570 hours (SD<0.0005) with dispersion of the nanoparticles within a polymer matrix, supporting the application of the drug-loaded MDDD in the management of ADC patients. The optimised multipolymeric nanoparticulate scaffold was implanted into the frontal lobe of the rat brain, for investigation of drug release characteristics and tissue response to the device following in vivo administration.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Medicine in Pharmaceutical Affairs Johannesburg, 2003 / Tshwane is one of three metropolitan municipalities in Gauteng Province and a cross border district with North West Province. Tshwane has a complex Drug Supply Management system. Gauteng Provincial Authority (GPA), North West Provincial Authority (NWPA) and City of Tshwane Metropolitan Municipality (CTMM) play significant roles. This has resulted in duplication of duties and inefficient use of resources. The aim of the study was to describe the current Drug Supply Management System in Tshwane, identify any weaknesses plus the factors responsible for the observed weaknesses and formulate recommendations for improvement. / IT2018

Antibiotic therapy has been proven to be vital for the treatment of life-threatening bacterial infections. Oral antibiotic therapy, however, results in unwanted side effects such as the intestinal flora destruction, allowing for the colonization of foreign bacteria. This phenomenon results in the occurrence of antibioticassociated diarrhea. Probiotic supplementation has been the choice adjunctive prophylaxis for this condition allowing for the bacterial adhesion of intestinal mucosal binding sites. Probiotic bacteria are, however, susceptible to the bactericidal effects of broad-spectrum antibiotics, resulting in many probiotic formulations being prescribed two hours after the ingestion of the antibiotic formulation. This is, however, not always adhered to, with many patients taking the antibiotic and probiotic concomitantly resulting in the destruction of the probiotic bacteria. This study provides for the design, development, characterization and evaluation of an oral delivery system for the concurrent administration of antibiotics and probiotics employing a dual release mechanism or ‘Dual-Biotic System’. The premise behind the development of this system is to allow for the concurrent administration of antibiotics and probiotics where the probiotic bacteria are only released two hours after the antibiotic, in which time the antibiotic would be absorbed into systemic circulation, preventing physical interaction between the systems and thus preventing bacterial destruction. Amoxicillin was chosen as the model antibiotic in this study due to its spectrum of activity and wide utilization in oral antibiotic therapy.

Thesis (M. Pharm.)--University of the Witwatersrand, Faculty of Health Sciences, 2013. / Ocular diseases of the anterior segment are ubiquitous, especially among elderly patients. The development of novel drug delivery systems on the journey for improved treatment is therefore imperative. Aside from anatomical and physiological barriers of the eye, the actual dosage form plays a crucial role. Although liquid eye drops are the first-choice dosage form, the shortcomings do not go unnoticed. In an attempt to circumvent these drawbacks, a novel instantly soluble eye drop device was developed. The system aimed to provide an easier administration form, comfort for the patient and improve drug bioavailability to anterior chamber. This was a steer toward attaining patient-convenience and compliance which are critically challenging factors. Preformulatory studies allowed for the screening and selection of candidate components and key processing conditions. Hydrophilic polymers and excipients were selected for attainment of small, rapid disintegrating yet robust matrices via lyophilization of solutions. Design of experiments generated formulations by means of a Face centred central composite design (FCCCD) that underwent thorough physicochemical and mechanical assessment. Overall, robust rapidly disintegrating solid eye drops were produced. Fastest disintegration time was noted to be 0.200s. Drug content ranged from 79-96%. An improved permeation of formulations compared to a pure drug dispersion was seen. Mathematical modeling was conducted for better insight into the behavior of the device on the eye surface. Statistical analysis through constraint optimization yielded a single optimal formulation. Thermal and molecular transition analysis showed congruent findings with no incompatibility between components. Combinatory surface morphology and porositometric studies confirmed the presence of interconnecting pores across the matrix surface. Drug release kinetic evaluation predicted that best model fit was first-order release. Ocular irritancy studies by means of the HET-CAM test indicated that both drug-loaded and drug-free eye drops had an irritation score of 0 with the inference of good tolerability. Ex vivo permeation across excised rabbit cornea showed an improved steady state drug flux (0.00052mg.cm-2.min-1) and permeability co-efficient (1.7x10-4cm.min-1) for the optimized device compared to pure drug and a marketed eye drop preparation. In vivo analysis was conducted on the rabbit model with insertion of the device into the ocular cul-de-sac. Subsequently, ultra performance liquid chromatography (UPLC) analysis of the aspirated aqueous humour for model drug timolol maleate detection was conducted. The device demonstrated improved drug levels (Cmax = 3ug/mL) in comparison to commercial eye drops (Cmax = 1.97ug/mL) and was well tolerated. Level A point-to-point IVIVC plots indicated a R2 value of 0.84. This served to imply that the in vitro dissolution data can be compared to and may serve as a surrogate to that of in vivo pK data. Histopathological assessment on the enucleated eye ball confirmed the lack of noxious effects of the device on ocular tissue. From this study, the solid eye drop device was concluded to be safe as a drug delivery system for the anterior eye. Looking toward innovative trends and modifications, a bi-layered solid eye drop system with enhanced permeability capabilities employing low molecular weight chitosan was further fabricated for preliminary investigation.

No description available.

Conotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus, which effectively treats patients suffering from severe chronic pain without consequent narcotic effects. Additionally, six other conotoxins have reached clinical trials and many novel ones are being discovered every day. Investigations reported in this dissertation broadens the applicability of conotoxins to non-excitable systems. Here, conotoxins from the dissected venom of the vermivorous cone snail Conus nux were isolated and purified by size exclusion and reverse phase HPLC and characterized by MALDI-TOF and MS/MS spectrometry. The purified conopeptide fractions revealed: 1) antagonist activity of conotoxin NuxVID on two human voltage-gated sodium channels, displaying capabilities as a practical molecular probe and a potential therapeutic lead. 2) Ability for two novel conotoxins to traverse artificial biological membranes, suggesting their potential as drug delivery systems. 3) In vitro capacity of several novel conopeptides to interfere with the adhesion of PfEMP1 domains, expressed in P. falciparum infected erythrocytes, to vascular endothelial and placenta receptors. Lastly, this work reveals binding of the synthetic form of α-conotoxin ImI, from the vermivorous cone snail Conus imperialis, to the α7 nAChR of macrophage-like-cells derived from the pre-monocytic leukemic cell line THP-1 in support of the involvement of this receptor in the cholinergic anti-inflammatory pathway. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection