Sustained release of antibiotic from poly(2-hydroxyethyl methacrylate) to prevent blinding infections after cataract surgery

Abstract

Intraocular lens implantation after opacified natural lens removal is the primary treatment for cataracts in developed countries. Cataract surgery is generally considered safe, but entails significant risks in countries where sophisticated sterile operating theaters are not widely available. Post-operative infection (endophthalmitis) is a potential blinding complication. Infection often results from bacterial colonization of the new lens implant and subsequent antibiotic-tolerant biofilm formation. To combat this risk, we developed a polymeric hydrogel system that can deliver effective levels of antibiotic over an extended period of time within the globe of the eye. Norfloxacin™ antibiotic was loaded into cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) gels, which were subsequently surface-modified with octadecyl isocyanate to produce a hydrophobic rate-limiting barrier controlling norfloxacin release. Octadecyl surface modification was characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A 15-min modification leads to a uniform surface coating and near zero order release of norfloxacin from the matrix. Norfloxacin released from coated pHEMA kills Staphylococcus epidermidis in suspension and on a simulated medical implant surface. With these data, we demonstrate a new and effective system for sustained drug release from a hydrogel matrix with specific application for intraocular lens surgery.

Digital drug delivery: on–off ultrasound controlled antibiotic release from coated matrices with negligible background leaching

“…However, similar studies have shown that no additional alkyl groups were observed on the surface of samples reacted with isocyanate for longer than 30 minutes. 21 Samples coated longer than 30 minutes appeared to swell and eventually degraded in the isocyanate-THF solution. Degradation was more apparent in more hydrophobic samples, i.e., samples with more HPMA component.…”

Recent advances in materials for extended-release antibiotic delivery system

“…18 The most common adverse event of antibiotics (for example, macrolides) is gastrointestinal (GI) stimulus that appears to be dose related; therefore, bypassing the absorption site in the upper GI tract is necessary especially in sustained-release preparations with larger dosage. It is known that variations of pH occur at GI tract, and hence application the pH-responsive carriers may be a solution.…”

pH‐Responsive Micelles Based on Amphiphilic Block Copolymers Bearing Ortho Ester Pendants as Potential Drug Carriers

“…[53] Based on previous studies on the same ortho ester structure, [54,55] the hydrolysis of the PEYM pendant chains should lead to the production of hydroxybutyric acid, ethanol, and poly(2-hydroxyethyl methacrylate), which is a hydrophilic polymer with excellent biocompatibility [56] and is widely used as drug carriers in the forms of microspheres, hydrogels, and nanogels, due to their strong intramolecular/intermolecular hydrogen bonding. [57,58] The kinetics of the PEYM side-chain hydrolysis can be quantified based on the released amount of hydrolyzed product (ethanol) and was determined using an enzyme-based assay. The time/pH-dependence of hydrolysis is shown quantitatively in Figure 3.…”