Currently, infections following cataract surgery are not as effectively managed with antibiotic eye drops, which suffer from poor bioavailability of drug and low patient compliance. The ideal solution, which can help to overcome the issue of drug wastage and poor bioavailabilty, as well as the need for frequent applications (patient inconvenience), is a drug-eluting intraocular lens (IOL). We describe a novel approach to such a drug-eluting lens by using a peripheral IOL attachment as a drug depot to deliver antibiotics, Levofloxacin (LFX) or Moxifloxacin (MFX). In this work, drug was entrapped within a fully-degradable polymer, poly(L-lactide-co-ɛ-caprolactone) (PLC). The effects of drug loading and solvent type on drug release and film morphology were investigated using cast films. The study clearly demonstrated that a slower-evaporating solvent tetrahydrofuran (THF) resulted in a better surface morphology, as well as lower initial burst compared to dichloromethane (DCM), and hence, was better suited to developing a drug-eluting attachment with sustained release of drug. When attachments were fabricated with drugs at high loading percentages (20% and 25% in polymer), significant burst was observed compared to films: this is attributed to the higher surface-to-volume ratio of the attachments. When the levofloxacin (LFX) loading percentage was decreased to 3% and 5%, the attachments presented lower burst and sustained release with therapeutic efficacy. This work has demonstrated the potential of using an IOL attachment as a more efficacious anti-infective option compared to daily eye drops.

This study reports on the release of a novel natriuretic peptide, CD-NP, from an in situ polymer precipitation delivery system. Following extensive screening of in-vitro release profiles, an in-vivo evaluation of the efficacy of the delivery system was carried out in Wistar rats. Gel injection was performed subcutaneously on the back of the rats. A secondary messenger, cyclic Guanosine 3′5′ Monophosphate (cGMP), was tested for verification of CD-NP bioactivity, in addition to direct measurements of CD-NP levels in plasma and urine using a radio-immuno assay. Plasma evaluation showed an elevated level of CD-NP over 3 weeks' duration. Unexpectedly, plasma cGMP level followed a decreasing trend over the same duration despite high CD-NP level. Loss of drug bioactivity was ruled out as a high level of CD-NP and cGMP excretion was observed in the treatment group as compared to baseline readings. This unexpected low-plasma cGMP levels and high-urinary cGMP excretion suggest that there might be other compensatory responses to regulation of the CDNP bioactivity as a result of the high drug dosing. The results stress the importance of assessing the overall bioactivity of released drug (in-vivo) concurrently in addition to measuring its concentrations, to determine the correct release profile.

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The in situ polymer precipitation delivery system has generated much interest over the last two decades. The ease of manufacturing and administering the delivery system are key advantages that have contributed to its increasing preference as a mode of drug delivery. Although much research has been performed on this system, the number of studies that have translated into animal models and subsequently into clinical trials is much lower than desired. This study aimed to investigate and understand the release mechanism and kinetics involved in peptide release from an in situ polymer precipitation system. Moreover, this study aimed to establish a correlation between the in vitroand in vivo-derived data. The ultimate aim was to identify a delivery system that can be used to deliver a novel therapeutic peptide, CD-NP, for the treatment of heart failure conditions. This study can be divided into 3 broad categories. First, in vitro studies were performed to characterise systemically the delivery system and its efficacy at achieving the prolonged release of the drug Cenderitide. Various gel formulation parameters were tested, i.e., the effect of polymer concentration, co-solvent, drug-loading and injected volume. The co-solvent system using the gel formulation 40% PLGA / 40% NMP / 20% triacetin was the most suitable for achieving the desired linear peptide release profile. Investigation of the solvent efflux and its influence on the drug release profile and shell structure formation morphology were also investigated. The Abstract x | P a g e solvent efflux and shell structure formation were found to be interdependent and affected the drug release profile. Second, feasibility studies were performed on both healthy and diseased Wistar rats. As

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