Implication of polymer properties on the manufacture and absorption of soft contact lenses used as drug carrier systems

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

Nanoparticle-laden contact lens for controlled ocular delivery of prednisolone : formulation optimization using statistical experimental design

Human eye is one of the most accessible organs in the body, nonetheless, its physiology and associated precorneal factors such as nasolacrimal drainage, blinking, tear film, tear turnover, and induced lacrimation has significantly decreased the residence time of any foreign substances including pharmaceutical dosage forms. Soft contact lenses are promising delivery devices that can sustain the drug release and prolong residence time by acting as a geometric barrier to drug diffusion to tear fluid. This study investigates experimental parameters such as composition of polymer mixtures, stabilizer and the amount of active pharmaceutical ingredient on the preparation of a polymeric drug delivery system for the topical ocular administration of Prednisolone. To achieve this goal, prednisolone-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by single emulsion solvent evaporation method. Prednisolone was quantified using a validated high performance liquid chromatography (HPLC) method. Nanoparticle size was mostly affected by the amount of co-polymer (PLGA) used whereas drug load was mostly affected by amount of prednisolone (API) used. Longer homogenization time along with higher amount of API yielded the smallest size nanoparticles. The nanoparticles prepared had an average particle size of 347.1 ± 11.9 nm with a polydispersity index of 0.081. The nanoparticles were then incorporated in the contact lens mixture before preparing them. Clear and transparent contact lenses were successfully prepared. When the nanoparticle (NP)-loaded contact lenses were compared with control contact lenses (unloaded NP contact lenses), a decrease in hydration by 2% (31.2% ± 1.25% hydration for the 0.2 g loaded NP contact lenses) and light transmission by 8% (unloaded NP contact lenses 94.5% NP 0.2 g incorporated contact lenses 86.23%). The wettability of the contact lenses remained within the desired value (<90 °C) even upon incorporation of the NP. NP alone and NP-loaded contact lenses both displayed a slow in vitro drug release of drug over 24 h; where 42.3% and 10.8% prednisolone release were achieved, respectively. Contact lenses can be used as a medicated device to sustain ocular drug delivery and improve patient compliance; nonetheless, patients and healthcare professionals' acceptability and perceptions of the new formulations entail further investigations

Feasibility of Using Nanoparticles of SiO2 to Improve the Performance of Recycled Aggregate Concrete

The aim of this paper was to examine the feasibility of using nanoparticles of SiO2 (nanosilica) to improve the performance of recycled aggregate concrete (RAC) containing recycled aggregate (RA) derived from processing construction and demolition waste of concrete buildings. The examined properties include compressive strength, splitting tensile strength, and water absorption. The study also includes examining the microstructure of RA and RAC with and without nanoparticles of SiO2. In total, nine mixes were investigated. Two mixes with RA contents of 50% and 100% were investigated and for each RA content; three mixes were prepared with three different nanoparticles dosages 0.4%, 0.8%, and 1.2% (by mass of cement). A control mix with natural aggregate (NA) was also prepared for comparison reasons. The results show that nanoparticles of silica can improve the compressive strength, tensile strength, reduce the water absorption, and modify the microstructure of RAC

Contact lenses as drug reservoirs & delivery systems : the successes & challenges

Although conventional eye drops comprise over 90% of the marketed ocular dosage forms, they do have limitations, such as poor ocular drug bioavailability and systemic side effects; contact lenses are amongst the new delivery systems and devices that could overcome some of these problems. The most common approach to load drug molecules into contact lenses includes soaking in a drug solution. This approach had some success, but failed to achieve controlled/sustained drug release to the eye. On the other hand, nanoreservoir systems comprising nanoparticles, cyclodextrins, liposomes or surfactant aggregates being incorporated into the contact lenses could offer a plausible solution. This review highlights the status quo with contact lenses as ocular drug-delivery carriers and identifies possible future directions. </jats:p