The research team, working with the vitamin E derivative D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and the triblock copolymer Poloxamer 188 (P188), set out to systematically optimize a mixed micellar carrier for the antibiotic. Their choice of polymers was deliberate. TPGS carries a bulky hydrophobic vitamin E succinate moiety attached to a polyethylene glycol chain, giving it a low critical micelle concentration and a strong capacity to form a compact, drug-friendly core. P188, a nonionic polyethylene oxide–polypropylene oxide–polyethylene oxide copolymer, is highly hydrophilic, biocompatible, and widely used in ophthalmic formulations for its steric stabilizing effect. Combining the two in different ratios, the researchers hypothesized, would let them fine-tune micellar packing, core–corona organization, and ultimately drug loading, release behavior, and permeation.

Preparation relied on the thin-film hydration technique. Ofloxacin, TPGS, and P188 were dissolved together in ethanol, and the solvent was removed under vacuum on a rotary evaporator to leave a uniform thin film. After drying overnight, the film was hydrated with phosphate-buffered saline at pH 7.4 and sonicated in a controlled bath kept below 30 degrees Celsius to protect the drug and polymers from thermal degradation. Before formulating, the team measured each polymer’s critical micelle concentration using iodine as a hydrophobic probe, finding values of 200 micrograms per milliliter for TPGS and 3 milligrams per milliliter for P188. Such low thresholds indicate that the micelles remain stable even when heavily diluted, an advantage for maintaining nanocarrier integrity under physiological conditions in the eye.

Nine formulations were screened, varying polymer identity, concentration, and drug-to-polymer ratio. The results revealed how strongly composition governs micellar architecture. Formulations built on TPGS alone produced uniformly small particles below 20 nanometers with narrow size distributions, consistent with tight hydrophobic core packing and effective steric shielding by the PEG corona. In stark contrast, P188-only systems ballooned into the micrometer range, forming loose aggregates rather than discrete nanomicelles, because the copolymer’s small polypropylene oxide block provides weak core stabilization. The hybrid systems fell between these extremes, and the balance proved decisive: modest amounts of P188 conferred stability, while excess of the highly hydrophilic copolymer gradually enlarged the particles and disturbed optimal packing.

Drug entrapment told an even sharper story. TPGS-rich micelles achieved entrapment efficiencies of roughly 80 to 89 percent, a figure the authors attribute to the compatibility between ofloxacin’s aromatic quinolone ring system and the compact, hydrophobic vitamin E succinate core, which supports hydrophobic, pi–pi, and hydrogen-bonding interactions. P188-only formulations trapped a dismal 8 to 11 percent, leaving most of the drug stranded in the external aqueous phase, while intermediate hybrid ratios reached only about 30 to 34 percent. The winning candidate, designated F8 and composed of 30 milligrams of TPGS with 20 milligrams of P188 per 10 milligrams of drug, delivered a particle size of 14.61 nanometers, a polydispersity index of 0.158, an entrapment efficiency of 88.7 percent, and a mildly negative zeta potential of −6.47 millivolts. That modest surface charge, combined with the steric barrier of the PEG chains, keeps the micelles from aggregating despite weak electrostatic repulsion.

Release testing in phosphate-buffered saline at 32 degrees Celsius, mimicking the ocular surface temperature, showed a characteristic biphasic pattern. An initial burst reflected ofloxacin molecules sitting near the micellar surface, followed by a prolonged sustained phase as drug entrapped deep in the hydrophobic core diffused out slowly. The optimized hybrid formulation released approximately 80 percent of its payload over ten hours, compared with less than 25 percent from a pure ofloxacin suspension, whose crystalline nature and limited solubility near physiological pH restrict dissolution. Kinetic modeling confirmed the mechanism: the Korsmeyer–Peppas model fit the F8 release data with a correlation coefficient of 0.9994 and a release exponent of 0.548, indicating anomalous, non-Fickian diffusion in which both molecular diffusion and relaxation of the micellar matrix contribute to drug liberation.

The most striking results came from ex vivo transcorneal permeation experiments using excised sheep corneas mounted in Franz diffusion cells. The optimized nanomicelles achieved a steady-state flux of 1.56 micrograms per square centimeter per minute, roughly eight times higher than the 0.19 micrograms per square centimeter per minute measured for the pure drug suspension. The lag time also shortened dramatically, from about 25 minutes for the suspension to roughly 10 minutes for the nanomicellar formulation. The researchers attribute this performance to nanomicelle-mediated solubilization of the drug and the intimate contact of nanosized carriers with the corneal surface, which promotes efficient partitioning of ofloxacin into the epithelial layer, the principal barrier to ocular drug entry.

Complementary structural analyses supported the encapsulation picture. Field-emission scanning electron microscopy showed spherical micelles of nanometer scale with a core–shell morphology. Differential scanning calorimetry revealed that the sharp melting endotherm of crystalline ofloxacin near 270 degrees Celsius vanished in the lyophilized formulation, indicating that the drug had been molecularly dispersed in an amorphous state within the micellar core, a transition generally associated with improved solubility. Fourier-transform infrared spectroscopy showed the drug’s characteristic carbonyl and aromatic bands attenuated and slightly shifted, without new peaks that would signal chemical incompatibility, while powder X-ray diffraction confirmed the complete loss of crystalline diffraction peaks upon entrapment.

The authors are careful to frame the work as a preclinical step rather than a clinical breakthrough. In vivo ocular residence time and antibacterial efficacy were not assessed and remain targets for future investigation, as do safety and long-term stability studies required before any clinical translation. Still, the platform’s appeal is broad. Unlike in situ gels and ocular inserts, which can cause blurred vision and foreign-body sensation, or niosomal vesicles, which suffer from larger sizes and cholesterol-related instability, polymeric nanomicelles form a clear, low-viscosity aqueous solution that patients would use much like conventional drops. And because the hybrid micellar strategy is not specific to ofloxacin, the team plans to extend it to other fluoroquinolones such as levofloxacin, potentially offering a general route to longer-acting, more penetrating topical antibiotics for the eye.

Subject of Research: Hybrid polymeric nanomicelles for improved ocular delivery of ofloxacin

Article Title: Hybrid polymeric nanomicelles for ocular delivery of ofloxacin: formulation optimization, release mechanism, and transcorneal permeation

Article References: Hussien, R. M., Kassab, H. J., & Mohamad, A. A. A. (2026). Hybrid polymeric nanomicelles for ocular delivery of ofloxacin: formulation optimization, release mechanism, and transcorneal permeation. Pharmacia, 73, Article e199144. https://doi.org/10.3897/pharmacia.73.e199144

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e199144

Keywords: ofloxacin, nanomicelles, TPGS, Poloxamer 188, ocular drug delivery, transcorneal permeation, drug release kinetics, cornea, fluoroquinolone, thin-film hydration, entrapment efficiency, ophthalmic formulations