Sustained In-Vivo Release of Triptorelin Acetate from a Biodegradable Silica Depot: Comparison to Pamorelin® LA

Abstract

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.

Capillary Electrophoresis–Mass Spectrometry with Multisegment Injection and In-Capillary Preconcentration for High-Throughput and Sensitive Determination of Therapeutic Decapeptide Triptorelin in Pharmaceutical and Biological Matrices

“…Table 6 provides a summary of chromatographic and electrophoretic methods used for determination of triptorelin in biological samples, i.e., plasma, serum, and urine. Determination of triptorelin has been typically performed with the use of liquid chromatography (LC) coupled with MS [25,[42][43][44][45][46][47] or UV detection [48,49]. Actually, the only CE method developed for biological samples is this one presented in our work.…”

Advancements and Applications of Injectable Hydrogel Composites in Biomedical Research and Therapy

“…Silica microparticles encapsulating triptorelin acetate formed an injectable depot with sustained release characteristics, exhibiting pharmacodynamic effects comparable to those of commercially available products [83]. The controlled release of bone morphogenetic protein-2 (BMP-2) from a three-dimensional tissue-engineered nano-scaffold resulted in significant ectopic bone formation, further underscoring its potential for tissue regeneration [84].…”

Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration

“…The biodegradation process does not change the pH within silica gel or in the surrounding tissue, in contrast to other commonly used polymeric LAI technologies. Further, it has been shown that the silica matrix is chemically and physically compatible with small molecules, monoclonal antibodies, peptides, and proteins. − …”