Matrix hyaluronic acid and bilayer poly-hydroxyethyl methacrylate-hyaluronic acid films as potential ocular drug delivery platforms.

This study aimed to design hydrogel based films comprising hyaluronic acid (HA) to overcome limitations of currently used eye drops. Timolol-loaded crosslinked (X2) HA-based and bilayer (B2) (pHEMA/PVP-HA-based layers) films were designed and characterized. The films were transparent (UV, visual observation) with crosslinked (<80 %) films showing lower light transmittance than bilayer (>80 %) films. X2 showed significantly higher swelling capacity, tensile strength and elastic modulus (5491.6 %, 1539.8 Nmm-2, 1777.2 mPa) than B2 (1905.0 %, 170.0N mm-2, 67.3 mPa) respectively. However, X2 showed lower cumulative drug released and adhesive force (27.3 %, 6.2 N) than B2 (57.5 %, 8.6 N). UV sterilization did not significantly alter physical properties, while SEM and IR microscopy showed smooth surface morphology and homogeneous drug distribution. Timolol permeation (EpiCorneal™/porcine cornea) depended on the film matrix with erodible films showing similar permeation to commercial eyedrops. Drug permeation for porcine cornea (X2 = 549.0.2, B2 = 312.1 µgcm-2 h-1) was significantly faster than EpiCorneal™ (X2 = 55.2, B2 = 37.6 µgcm-2 h-1), but with a linear correlation between them. All the selected optimized films showed acceptable compatibility (MTT assay) with both HeLa cells and EpiCorneal™. In conclusion, crosslinked and bilayer HA based films showed ideal characteristics suitable for potential ocular drug delivery, though further work is required to further optimize these properties and confirm their efficacy including in vivo tests.

Development of 3D printed drug-eluting contact lenses.

OBJECTIVES: The aim of the work was to introduce 3D printing technology for the design and fabrication of drug-eluting contact lenses (DECL) for the treatment of glaucoma. The development of 3D printed lenses can effectively overcome drawbacks of existing approaches by using biocompatible medical grade polymers that provide sustained drug release of timolol maleate for extended periods. METHODS: Hot melt extrusion was coupled with fusion deposition modelling (FDM) to produce printable filaments of ethylene-vinyl acetate copolymer-polylactic acid blends at various ratios loaded with timolol maleate. Physicochemical and mechanical characterisation of the printed filaments was used to optimise the printing of the contact lenses. KEY FINDINGS: 3D printed lenses with an aperture (opening) and specified dimensions could be printed using FDM technology. The lenses presented a smooth surface with good printing resolution while providing sustained release of timolol maleate over 3 days. The findings of this study can be used for the development of personalised DECL in the future.

Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma.

Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.