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Polymer-based systems are often considered a necessity for controlled drug delivery, but have well-known limitations. Here, the authors report on drug delivery implants formed solely from corticosteroid dimers, which demonstrate controlled release and overcome many of the challenges of polymer-based systems.

While the use of topical drops for the delivery of drugs to the anterior of the eye is well accepted, it is far from efficient with as little as 5% of the drug instilled on the eye actually reaching the target tissue. The ability to prolong the residence time on the eye is desirable. Based on the acceptability of 2-hydroxyethyl methacrylate based polymers in contact lens applications, the current work focuses on the development of a poly(2-hydroxyethyl methacrylate (HEMA)) nanoparticle system. The particles were modified to allow for degradation and to permit mucoadhesion. Size and morphological analysis of the final polymer products showed that nano-sized, spherical particles were produced. FTIR spectra demonstrated that the nanoparticles comprised poly(HEMA) and that 3-(acrylamido)phenylboronic acid (3AAPBA), as a mucoadhesive, was successfully incorporated. Degradation of nanoparticles containing N,N′-bis(acryloyl)cystamine (BAC) after incubation with DL-dithiothreitol (DTT) was confirmed by a decrease in turbidity and through transmission electron microscopy (TEM). Nanoparticle mucoadhesion was shown through an in-vitro zeta potential analysis.

The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA) into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v) and a 1 mg/mL dexamethasone phosphate solution (0.1%) was prepared in borate buffered saline. Three hydrogel material samples (pHEMA; pHEMA TRIS; DMAA TRIS) were prepared with and without the covalent incorporation of HA of molecular weight (MW) 35 or 132 kDa. Hydrogel discs were punched from a sheet of material with a uniform diameter of 5 mm. Uptake kinetics were evaluated at room temperature by soaking the discs for 24 h. Release kinetics were evaluated by placing the drug-loaded discs in saline at 34 °C in a shaking water bath. At various time points over 6–7 days, aliquots of the release medium were assayed for drug amounts. The majority of the materials tested released sufficient drug to be clinically relevant in an ophthalmic application, reaching desired concentrations for antibiotic or anti-inflammatory activity in solution. Overall, the silicone-based hydrogels (pHEMA TRIS and DMAA TRIS), released lower amounts of drug than the conventional pHEMA material (p < 0.001). Materials with HA MW132 released more ciprofloxacin compared to materials with HA MW35 and lenses without HA (p < 0.02). Some HA-based materials were still releasing the drug after 6 days.

Contact lenses, as an alternative drug delivery vehicle for the eye compared to eye drops, are desirable due to potential advantages in dosing regimen, bioavailability and patient tolerance/compliance. The challenge has been to engineer and develop these materials to sustain drug delivery to the eye for a long period of time. In this study, model silicone hydrogel materials were created using a molecular imprinting strategy to deliver the antibiotic ciprofloxacin. Acetic and acrylic acid were used as the functional monomers, to interact with the ciprofloxacin template to efficiently create recognition cavities within the final polymerized material. Synthesized materials were loaded with 9.06 mM, 0.10 mM and 0.025 mM solutions of ciprofloxacin, and the release of ciprofloxacin into an artificial tear solution was monitored over time. The materials were shown to release for periods varying from 3 to 14 days, dependent on the loading solution, functional monomer concentration and functional monomer:template ratio, with materials with greater monomer:template ratio (8:1 and 16:1 imprinted) tending to release for longer periods of time. Materials with a lower monomer:template ratio (4:1 imprinted) tended to release comparatively greater amounts of ciprofloxacin into solution, but the release was somewhat shorter. The total amount of drug released from the imprinted materials was sufficient to reach levels relevant to inhibit the growth of common ocular isolates of bacteria. This work is one of the first to demonstrate the feasibility of molecular imprinting in model silicone hydrogel-type materials.

The efficiency of drug delivery to the eye using topical drop therapy is limited by the ocular clearance mechanisms. Nanocarriers, able to encapsulate bioactive compounds and slow down their release, may allow for prolonged on-eye residence times when combined with topical application for treatment of ocular conditions. Previously, self-assemblies of methylcellulose (MC) hydrophobized with N-tert-butylacrylamide side chains (MC-g-PNtBAm) were developed. The purpose of the current study was to investigate the impact of the methylcellulose backbone length on the properties of the nanogels. We synthesized MC-g-PNtBAm nanogels using four different molecular weights of MC with two degrees of hydrophobic modification and investigated the physical and chemical properties of the resulting polymeric nanogels. While no significant change could be observed at a high degree of hydrophobization, properties were affected at a lower one. Increasing the molecular weight of MC improved the swelling capacity of the nanogels, increasing their size in water. An effect on the drug release was also noted. Nanogels prepared using MC with a molecular weight of 30 kDa did not retain as much dexamethasone and released it faster compared to those prepared using 230 kDa MC. Thus, besides the degree of hydrophobization, the length of MC chains provides another means of tuning the properties of MC-g-PNtBAm nanogels.