Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings

Abstract

Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio-surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano-fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano-structured coatings (for all formulations) were <200nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM-loaded PNIPAM coating releasing most drug after 24h (89.8%). Kinetic modelling (Higuchi, Korsmeyer-Peppas) was indicative of quasi-Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating method demonstrates sustained drug release yielding promising results; suggesting both novel device and method to enhance drug activity at the eyes surface which will reduce formulation drainage.

Development of random and ordered composite fiber hybrid technologies for controlled release functions

“…TE-HCL was only incorporated in PVP membranes for constructs P1-P5. Quasi-Fickian diffusion as demonstrated in previous studies since n is below 0.5 [40].…”

Self-Assembling Peptide Nanofiber Hydrogels for Controlled Ocular Delivery of Timolol Maleate

“…9 Recently, electrohydrodynamic atomization was employed for ocular drug delivery applications through fiber coating of contact lenses, showing the potential of the platform in reducing drug drainage and increasing drug transport across the cornea. [10][11][12][13] Self-assembling peptide hydrogels constitute a class of bio-inspired materials, which have been tested in a plethora of biomedical applications, including tissue engineering and regenerative medicine [14][15][16] and controlled drug release. [17][18][19][20][21] These peptides have a hydrophobic side and a hydrophilic side which contains alternating positively and negatively charged residues.…”

Assessing the ex vivo permeation behaviour of functionalised contact lens coatings engineered using an electrohydrodynamic technique

“…Coating engineering Previous work carried out in this area [17,18] has already showed the novel lens holder used here was able to accommodate up to 4 lenses whilst keeping the lenses stable and stationary during the deposition process. A masked arm was used to ensure only the peripheral regions of the lenses were coated so as not to obstruct vision.…”

“…Electrohydrodynamic atomisation (EHDA), more specifically electrospinning was utilised in this instance to engineer fibrous coatings for contact lens surfaces. The on-demand, cost effective process has already shown its potential in an array of applications [7] including wound management [8][9][10][11][12][13], drug delivery [14][15][16][17][18][19][20][21][22] bioengineering [23][24][25][26] and theranostics [27]. Here, electrospun fibrous coatings were engineered to assess the ex vivo release and permeation of TM through freshly excised cornea as an extension of previous work [18].…”