No abstract

No abstract

No abstract

No abstract

Poly(2‐hydroxyethyl methacrylate) (pHEMA) hydrogels are well known in ophthalmological applications and recently investigated as drug delivery systems. The study represents a theoretical approach where the sorption/desorption experiments and spectroscopic study is used to describe the influence of the pHEMA network structure on the sorption capacity and mechanism of the release of topotecan (TPT) and vincristine (VCR). The hydrogels are synthesized by free‐radical crosslinking polymerization of HEMA monomer with ethylene glycol dimethacrylate as a crosslinker in the concentration range from 0.3 to 1 wt%. Experimental data from sorption kinetics are evaluated using sorption kinetic models and sorption isotherms, drug release mechanism is assessed by two different models and attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy is employed to describe the polymer‐drug interaction. pHEMA hydrogels exhibit higher affinity for TPT than for VCR and hydrogels prepared with 0.5 wt% of crosslinker show the maximum sorption capacity for both drugs. Physisorption is proved to be the sorption mechanism. Analyzing the FTIR spectra, it is concluded that the hydrophobic crosslinks play an important role in the interaction of the hydrogel backbone with molecules of both drugs.

No abstract

No abstract

Transscleral diffusion delivery of chemotherapy is a promising way to reach the vitreal seeds of retinoblastoma, the most common intraocular malignancy in childhood. In this in vivo study, the delivery of topotecan via lens-shaped, bi-layered hydrogel implants was combined with transconjunctival cryotherapy to assess whether cryotherapy leads to higher concentrations of topotecan in the vitreous. The study included 18 New Zealand albino rabbits; nine rabbits received a topotecan-loaded implant episclerally and another nine rabbits received transconjunctival cryotherapy superotemporally 2 weeks before implant administration. Median vitreous total topotecan exposures (area under the curve, AUC) were 455 ng·h/mL for the cryotherapy group and 281 ng·h/mL for the non-cryotherapy group, and were significantly higher in the cryotherapy group, similar to maximum levels. Median plasma AUC were 50 ng·h/mL and 34 ng·h/mL for the cryotherapy and non-cryotherapy groups, respectively, with no statistically significant differences between them. In both groups, AUC values in the vitreous were significantly higher than in plasma, with plasma exposure at only approximately 11–12% of the level of vitreous exposure. The results confirmed the important role of the choroidal vessels in the pharmacokinetics of topotecan during transscleral administration and showed a positive effect of cryotherapy on intravitreal penetration, resulting in a significantly higher total exposure in the vitreous.