Zero‐Order Antibiotic Release from Multilayer Contact Lenses: Nonuniform Drug and Diffusivity Distributions Produce Constant‐Rate Drug Delivery

Abstract

A novel approach to zero-order constant-rate drug delivery from contact lenses is presented. Quasi-Case II non-Fickian transport is achieved by nonuniform drug and diffusivity distributions within three-layer bimodal amphiphilic conetworks (β-APCNs). The center layer is a highly oxygen permeable β-APCN matrix, which contains the drug and exhibits a high drug diffusivity. The outer β-APCN layers contain no-drug and are loaded with vitamin E, which slows diffusion. In contrast to single-layer neat-polymer and vitamin E-loaded films that display first-order "burst" kinetics, it is demonstrated experimentally and by modeling that the combined effect of nonuniform distribution of drug loading and diffusion constants within the three-layer lens maintains low local drug concentration at the lens-fluid interface and yields zero-order drug delivery. The release rates of topical antibiotics provide constant-rate therapeutic-level delivery with appropriate oxygen permeability for at least 30 h, at which time ≈25% of the drug was released.

Amphiphilic Polymer Conetworks Based on Interconnected Hydrophobic Star Block Copolymers: Synthesis and Characterization

“…[9] Finally, because nanophase separation within these materials leads to the formation of a large interfacial area, APCNs have been used as the scaffolds for phase transfer catalysis, both enzymatic and organocatalysis. [10] Other, recent publications on APCNs report constant rate antibiotic release from a contact lens based on three APCN layers, with the two external layers imbibed with vitamin E which acts as a diffusion barrier, [11] and tissue regeneration from ovine corneal endothelial cells attached on crystallizable and degradable APCNs. [12] Further investigations in the field of APCNs describe the fabrication of biocidal macroporous cryogel APCNs based on cross-linked diblock copolypeptides, [13] the development of highly conductive, tough, ion APCNs, [14] the formation of APCNs comprising highly interacting poly(propylene glycol) and poly(N-vinylimidazole) segments, [15] the preparation of microcrystalline APCNs based on all-oxazoline blocks, [16] and the synthesis of carboxylate-bearing APCNs, non-susceptible to abrupt shrinkage in the presence of calcium cations.…”

“…Such more regular morphologies will result in APCNs better-suited for all above-mentioned applications. [6][7][8][9][10][11][12][13][14] Experimental Section Polymer synthesis was performed using one-pot, sequential group transfer polymerization (GTP) [30][31][32] under anhydrous conditions and using Schlenk techniques. The molecular weights of the star polymers were characterized using gel permeation chromatography (GPC, chromatograph from Polymer Laboratories using a PL-Mixed "D" column) with dual refractive index (RI, RL-RI800 detector) and static light scattering (SLS, BI-MwA spectrophotometer from Brookhaven) detection, whereas the molecular weights of the cores of the stars were characterized using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (UltraFlex III MALDI spectrometer from Bruker, equipped with a Nd:YAD laser, together with dithranol as the matrix and sodium trifluoroacetate as the cationization salt).…”

Novel Anti‐Biofouling Soft Contact Lens: l‐Cysteine Conjugated Amphiphilic Conetworks via RAFT and Thiol–Ene Click Chemistry

“…The silicone hydrogels with amphiphilic conetwork (APCN) structure have been specifically developed for soft contact lenses with dramatically improvement of oxygen permeability. The cocontinuous microphase morphology in APCNs is achieved by skillful combination of the hydrophilic phase with the hydrophobic polydimethylsiloxane phase, which perfectly matches the need of extended‐wear contact lenses …”

“…The cocontinuous microphase morphology in APCNs is achieved by skillful combination of the hydrophilic phase with the hydrophobic polydimethylsiloxane phase, which perfectly matches the need of extended-wear contact lenses. [5][6][7][8] Most APCNs are prepared by conventional free radical polymerization, [9][10][11][12] and the resultant conetworks generally possess bicontinuous microphase separation morphologies and the optical transparency is obtained when the microphase size is less than 100 nm. [1,[13][14][15] However, the APCN synthesis via free radical polymerization may be accompanied by some unavoidable imperfections, for example, although complete conversion of bismacromonomers is reported, [16] dangling chains may be formed by incomplete incorporation of the bifunctional cross-linker, which may lead to poor conformation regularity and structural defects in the conetworks.…”

Double‐networks based on interconnected amphiphilic “in–out” star first polymer conetworks prepared by RAFT polymerization

“…This means that these first network components were amphiphilic polymer conetworks (APCN), an important macromolecular entity possessing the properties of hydrogels and block copolymer surfactants, i.e., swelling and self-assembly in water, respectively. [23][24][25][26] In turn, this would imply that the final DN hydrogels would also bear the hydrophobic cores of the self-assembled APCN first networks, which may be exploited for drug delivery, 27,28 tissue engineering, 29 solid or gel polymer electrolytes, [30][31][32][33] but also for organic or enzymatic phase transfer catalysis. 34 In the present report, we extend our previous work on DN hydrogels based on well-defined APCN first networks comprising interconnected amphiphilic star copolymers.…”