Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

PurposeIntravitreal (IVT) therapies are a standard of care for many ocular diseases. Frequent administration and injection‐based adverse events pose a hurdle for effective upkeep of ocular health. Developing improved effective treatment durations has gained significant traction. This study investigated if a near water‐insoluble drug, BAY224, could be encapsulated in biodegradable silica microparticles (SMP) and exhibit sustained controlled in vitro and in vivo release through a surface eroding SMP‐silica hydrogel composite (silica‐silica composite).MethodsBAY224 was encapsulated in a silica matrix by sol‐gel chemistry and spray drying. In vitro silica dissolution and BAY224 release from silica‐silica composite was analyzed followed by studying in vivo IVT release in rabbits. In vitro silica dissolution was studied in sink conditions colorimetrically. Cumulative release and total BAY224 content were analyzed by HPLC. In vivo release was studied by LC‐MS/MS of sample vitreous humor up to 55 days post 30 µl IVT injections.ResultsBAY224 was encapsulated, and silica‐silica composite was made at a load of 1 mg/50 µL (5.7 wt‐%). BAY224‐SMPs were sterilized using γ‐irradiation (26.8–47.5 kGy) not affecting in vitro dissolution. Burst release of BAY224 was >9 wt‐% in SMP and silica‐silica composite. Release of API was controlled by silica matrix surface erosion. In accelerated in vitro dissolution, the release time of BAY224 from SMP was 8–9 days. The silica‐silica composite prolonged release to 9–10 days. With the relevant in vitro‐in vivo correlation factor, in vivo release of 3 months was hypothesized. In vivo PK data showed sustained release of BAY224 in vitreous for at least 55 days. Daily API release (calculated from the API remnant in depot) was ca. 5–8 µg/day.ConclusionsEfficient encapsulation of a near insoluble drug was achieved with a silica‐silica composite with no burst release and a long‐acting release in‐vivo of >55 days in line with the in‐vitro dissolution results.

Bioactive fibers have become increasingly prevalent for applications in optical sensing and as reinforcement in fully biodegradable devices. However, the typical bioactive glass fibers drawn from silicate glasses have poor mechanical properties. Here, we present our latest study on the development of new bioactive single‐core (SC) borophosphate fiber with the composition (in mol%) 47.5P2O5‐20CaO‐20SrO‐10Na2O‐2.5B2O3 and of core‐clad (CC) borophosphate fiber, the composition (in mol%) of the clad and the core being 47.5P2O5‐20CaO‐20SrO‐10Na2O‐2.5B2O3 and 0.025CeO2‐0.975(47.5P2O5‐20CaO‐20SrO‐10Na2O‐2.5B2O3), respectively. We show that the immersion in aqueous solutions such as Tris(hydroxymethyl)aminomethane (TRIS) increases first the mechanical properties of the fibers due to the early congruent glass dissolution and so due to the reduction in the density of surface flaws. However, for long immersion in TRIS or in Simulated Body Fluid (SBF), the mechanical properties decrease due to the precipitation of a reactive calcium‐phosphate layer at the surface of the fibers. Especially when immersed for a long time in SBF, the fibers become too fragile to allow one to measure their mechanical properties. Nonetheless, we clearly show in this study that the newly developed fibers are promising materials for reinforcing composite and/or as biosensors as these fibers still possess sufficiently high mechanical properties after immersion for significant time in SBF and/or TRIS.

No abstract