Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis

Gallagher, Andrew; McLean, K. Robin; Stewart, Rosalind M K; Wellings, Don A.; Allison, Heather E.; Williams, Rachel

doi:10.1167/iovs.17-22301

Cited by 22 publications

(25 citation statements)

References 23 publications

(31 reference statements)

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“…A significant advantage of pεK hydrogels is that we can tailor the mechanical properties of the pεK hydrogel to fit specific requirements. In this study, a pεK hydrogel with polymer density 0.066 g/ml cross-linked to 60% with octanedioic-acid was initially used as previous research had demonstrated that this pεK hydrogel was robust enough to handle easily [38, 39]. The pεK hydrogels had a modulus of 0.11 MPa and ultimate tensile strength of 0.04 MPa.…”

Section: Discussionmentioning

confidence: 99%

“…Synthetic hydrogels are an attractive option for CE replacement as they would allow the diffusion of water and biomolecules into the stroma. Our previous studies have shown that poly-ε-lysine (pεK) cross-linked with octanedioic-acid produces hydrogels that are transparent, are non-toxic to corneal epithelial cells in vitro and can be cast into contact lens moulds [38, 39]. In addition, following crosslinking of pεK hydrogels, free amine sites remain for either electrostatic or covalent binding of drugs, proteins or peptides to the pεK hydrogel.…”

Section: Introductionmentioning

confidence: 99%

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Poly-ε-lysine based hydrogels as synthetic substrates for the expansion of corneal endothelial cells for transplantation

Kennedy

Lace

Carserides

et al. 2019

J Mater Sci: Mater Med

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Dysfunction of the corneal endothelium (CE) resulting from progressive cell loss leads to corneal oedema and significant visual impairment. Current treatments rely upon donor allogeneic tissue to replace the damaged CE. A donor cornea shortage necessitates the development of biomaterials, enabling in vitro expansion of corneal endothelial cells (CECs). This study investigated the use of a synthetic peptide hydrogel using poly-ε-lysine (pεK), cross-linked with octanedioic-acid as a potential substrate for CECs expansion and CE grafts. PεK hydrogel properties were optimised to produce a substrate which was thin, transparent, porous and robust. A human corneal endothelial cell line (HCEC-12) attached and grew on pεK hydrogels as confluent monolayers after 7 days, whereas primary porcine CECs (pCECs) detached from the pεK hydrogel. Pre-adsorption of collagen I, collagen IV and fibronectin to the pεK hydrogel increased pCEC adhesion at 24 h and confluent monolayers formed at 7 days. Minimal cell adhesion was observed with pre-adsorbed laminin, chondroitin sulphate or commercial FNC coating mix (fibronectin, collagen and albumin). Functionalisation of the pεK hydrogel with synthetic cell binding peptide H-Gly-Gly-Arg-Gly-Asp-Gly-Gly-OH (RGD) or α2β1 integrin recognition sequence H-Asp-Gly-Glu-Ala-OH (DGEA) resulted in enhanced pCEC adhesion with the RGD peptide only. pCECs grown in culture at 5 weeks on RGD pεK hydrogels showed zonula occludins 1 staining for tight junctions and expression of sodium-potassium adenosine triphosphase, suggesting a functional CE. These results demonstrate the pεK hydrogel can be tailored through covalent binding of RGD to provide a surface for CEC attachment and growth. Thus, providing a synthetic substrate with a therapeutic application for the expansion of allogenic CECs and replacement of damaged CE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Poly-ε-lysine based hydrogels as synthetic substrates for the expansion of corneal endothelial cells for transplantation

Kennedy

Lace

Carserides

et al. 2019

J Mater Sci: Mater Med

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Section: Methodsmentioning

confidence: 99%

“…The fabrication of pɛK hydrogels (cross-linked to 60 mol% with octanedioic acid to a polymer density of 0.071 g mL −1 ), pɛK functionalization, sterilization, and wash steps were performed as previously described. 26,29 Bacterial Strains and Culture Conditions P aeruginosa (PAO1) (ATCC 47085) and clinical keratitis isolates (cytotoxic strain exoU + PA39016 and invasive strain exoS + PA58017) (kindly donated by Prof. C. Winstanley, University of Liverpool, Liverpool, UK), 30 were cultured overnight on Luria-Bertani (LB) agar (Sigma-Aldrich, Dorset, UK) plates at 37°C. Five milliliters of LB broth (Sigma-Aldrich) was inoculated with bacteria and cultured for 18 hours with shaking (120 rpm/min), at 37°C.…”

Section: Pɛk Hydrogel Synthesis and Functionalizationmentioning

confidence: 99%

Antimicrobial Activity of Poly-epsilon-lysine Peptide Hydrogels Against Pseudomonas aeruginosa

Kennedy

Deshpande

Gallagher

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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To determine the antimicrobial activity of poly-epsilon-lysine (pɛK) functionalization of hydrogels against Pseudomonas aeruginosa. METHODS. Antimicrobial activities of pɛK and pɛK+ hydrogels were tested against both keratitis and a laboratory strain of P aeruginosa at a range of inocula sizes, over 4 and 24 hours. The number of viable CFU on pɛK and pɛK+ hydrogels or commercial contact lenses (CL) was investigated. Ex vivo porcine corneas were inoculated with P aeruginosa PAO1 (10 3 CFU) and incubated with pɛK+ hydrogels or commercial hydrogel CL for 24 hours and the effects of infection determined. RESULTS. PɛK+ hydrogels showed log reductions in viable CFU compared with pɛK hydrogels for all P aeruginosa strains, depending on inocula sizes and incubation time. After 24 hours pɛK+ hydrogels showed >5 and >7.5 log reduction in CFU compared with commercial hydrogel CL at 10 3 and 10 6 CFU, respectively. In an ex vivo porcine corneal infection model, pɛK+ hydrogels led to a significant decrease in viable PAO1 CFU and histologic analysis indicated a decreased infiltration of PAO1 into the stroma. CONCLUSIONS. PɛK+ hydrogels demonstrated enhanced antimicrobial activity versus nonfunctionalized pɛK hydrogels against clinically relevant P aeruginosa strains. PɛK+ hydrogels have the potential to be used as a bandage CL with innate antimicrobial characteristics to minimize the risk of microbial keratitis.

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“…In recent years, several examples of the mentioned drugs have been incorporated into CLs using many different techniques, and the obtained results have been extensively discussed in previous review papers [21,111,186]. Therapeutic CLs for the treatment of keratitis have also been widely reported in literature reviews [187,188], with promising results for the delivery of biocides [189,190], antifungals [189,[191][192][193][194], and antiviral drugs [195,196].…”

Section: Corneal Diseasesmentioning

confidence: 99%

Therapeutic Ophthalmic Lenses: A Review

2020

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An increasing incidence of eye diseases has been registered in the last decades in developed countries due to the ageing of population, changes in lifestyle, environmental factors, and the presence of concomitant medical conditions. The increase of public awareness on ocular conditions leads to an early diagnosis and treatment, as well as an increased demand for more effective and minimally invasive solutions for the treatment of both the anterior and posterior segments of the eye. Despite being the most common route of ophthalmic drug administration, eye drops are associated with compliance issues, drug wastage by lacrimation, and low bioavailability due to the ocular barriers. In order to overcome these problems, the design of drug-eluting ophthalmic lenses constitutes a non-invasive and patient-friendly approach for the sustained drug delivery to the eye. Several examples of therapeutic contact lenses and intraocular lenses have been developed, by means of different strategies of drug loading, leading to promising results. This review aims to report the recent advances in the development of therapeutic ophthalmic lenses for the treatment and/or prophylaxis of eye pathologies (i.e., glaucoma, cataract, corneal diseases, or posterior segment diseases) and it gives an overview of the future perspectives and challenges in the field.

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Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis

Cited by 22 publications

References 23 publications

Poly-ε-lysine based hydrogels as synthetic substrates for the expansion of corneal endothelial cells for transplantation

Poly-ε-lysine based hydrogels as synthetic substrates for the expansion of corneal endothelial cells for transplantation

Antimicrobial Activity of Poly-epsilon-lysine Peptide Hydrogels Against Pseudomonas aeruginosa

Therapeutic Ophthalmic Lenses: A Review

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