Mustafa, Shelan (2020) Implication of polymer properties on the manufacture and absorption of soft contact lenses used as drug carrier systems. (PhD thesis), Kingston University, .
Abstract
Background: Glaucoma is one of the leading causes of vision loss, where it is found in 2% of the population over the age of 40. It is estimated that more than 500,000 people suffer from glaucoma in England and Wales alone, with more than 70 million affected across the world. Conventional treatments start with topical anti-glaucoma medications such as eye drops. Soft contact lenses (SCLs) can substitute eye drops and ocular ointments. They help improve drug bioavailability, residence time and drug delivery to the targeted site, leading to compromised patient compliance. Aim: This study focused on developing new SCLs using hydrophilic and hydrophobic polymers; which were further investigated as potential carriers for drozolamide hydrochloride (DZH). Surfactants to modulate drug release as well as improve SCL properties. Experimental: Si-Hy SCLs were prepared via UV-polymerisation. PAA NPs were prepared via ionic gelation using calcium chloride a cross-linking agent; they were incorporated into SCLs. A bacterial adherence study was conducted on the SCLs. The two pathogenic microorganisms investigated were Staphylococci epidermidis and Pseudomonas aeruginosa. Post SCLs polymerisation characterisation studies were carried out to investigate EWC, CA, TM, YM and in vitro drug release. Ocular toxicity studies (HETCAM and BCOP assays) were undertaken to identify any potential ocular irritation associated with these SCLs. Results: PDMS-AS displayed the highest EWC% followed by TFMS, PDMS-VT and TRIS. All of these silicones based polymers possessed promising qualities that could be of benefit when preparing SCLs. F-S/A gave rise to the transparent SCLs, whilst PDMS-AS had the highest EWC%. Combining the silicone based polymers with HEMA hydrogel, could potentially eliminate lens-induced hypoxia for SCL wearers, due to the high oxygen permeable nature of siloxane and the hydrophilic HEMA hydrogel will provide the required hydration and comfort for SCL wearers. It was found that polyacrylic acid (PAA) concentration affected the NP size, low PAA concentration proved to be the most promising to achieve the smallest particle size (200nm) and PDI values (0.048). Incorporation of DZH into NPs increased their mean particle size. Entrapment efficiency of DZH was 81%, which is sufficient to achieve a therapeutic dose. In vitro drug release studies have demonstrated that this new platform could potentially sustain DZH release, lowering IOP over extended periods of time, beyond what is achieved with conventional eye drops. Bacterial adherence studies revealed that incorporation of P407 aided the resistance of both gram negative and gram-positive bacteria when compared to the controls. Both irritation assays (HET-CAM and BCOP) revealed that the developed SCLs were devoid of potential conjunctiva and corneal irritation. Conclusion: modified SCLs could be formulated using a blend of silicon and HEMA with improved properties. The carbonic anhydrase inhibitor (DZH) can be loaded into these modified SCLs to achieve sustained drug release and potentially improve patient compliance. Polymeric NPs can be loaded into these SCLs with minimal effect on their properties. P407 surfactant has been shown to be essential to minimise bacterial adherence to the surface of SCLs, hence minimise the chance of microbial keratitis.
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