Development of injectable long‐acting controlled release intravitreal depot of BAY224 using biodegradable silica microparticle‐silica hydrogel composite

Abstract

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.

Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability

“…The in vivo safety profile of silica nanoparticles has been previously addressed, offering a propitious approach for the ocular topical delivery of drugs [ 22 , 23 ]. Using silica nanoparticles as drug carriers for ocular delivery has been introduced several times in the literature [ 24 , 25 , 26 ].…”

Long-Acting Gel Formulations: Advancing Drug Delivery across Diverse Therapeutic Areas

“…Intravitreal injection [34] Creating a long-acting subconjunctival in situ gelling implant for glaucoma treatment.…”

“…The encapsulation of BAY224 in biodegradable silica microparticles within a silica hydrogel was investigated for its controlled release both in vitro and in rabbits over 55 days. This method showed promise for long-acting intravitreal therapy, which could decrease the need for frequent injections and improve patient compliance in treating ocular diseases [ 34 ].…”

“…Research in neuroendocrine disorders and acromegaly has demonstrated a shift towards long-acting formulations, such as lanreotide Autogel, to ensure consistent and manageable treatment options for patients, with the goal of optimizing therapeutic effectiveness and improving quality of life [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. The investigation into ophthalmic applications and pain management reveals a significant demand for long-acting gels to improve adherence to treatment, reduce the frequency of administration, and increase patient comfort in managing conditions like glaucoma and chronic pain [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”