A study of the dexamethasone sodium phosphate release properties from a periocular capsular drug delivery system

Abstract

The aim of this study was to investigate whether a periocular capsular drug delivery system (DDS) can release dexamethasone sodium phosphate (DEXP) in vitro and in vivo to the posterior segment of rabbit's eye. In vitro, the periocular capsular DDS containing 2 mg/ml or 5 mg/ml DEXP was immersed in modified Franz diffusion cell. Four-hundred microliters of liquid was aspirated at 0.5, 1, 2, 4, 8, 24 and 48 h for determination. In vivo, the DEXP-filled periocular capsular DDS was implanted into the sub-Tenon's sac of the New Zealand rabbit. DEXP concentration at the serum aqueous humor, cornea, iris, lens, ciliary body, vitreous, retina, choroids and sclera was quantified at 1, 3, 7, 14, 28 and 56 d after implantation. The DEXP concentration was determined by ultra-performance liquid chromatography-tandem mass spectrometry. In vitro, the periocular capsular DDS released the DEXP in time-dependent manner from 1/2 to 48 h. In vivo, the concentrations of the DEXP at the retina, choroids, ciliary body and iris were 123.11 (91.23, 732.61) ng/g, 362.46 ± 330.46 ng/g, 71.64 (71.35, 180.21) ng/g and 192.50 ± 42.66 ng/g, respectively, at 56 d after implantation. Minimal DEXP was found in the aqueous, serum and vitreous. Our results demonstrated that DEXP could be sustained released from the periocular capsular DDS, which indicated that the periocular capsular DDS might be a potential candidate of transscleral drug delivery for the management of posterior segment diseases.

Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit

“…When a depot corticosteroid preparation is injected subconjunctivally and side effect occurs, the remainder of the depot can be surgically removed (Huang et al, 2016), it is similar in CCSDD. Intrascleral drug delivery to the eye using hollow microneedles can infuse solutions into the sclera for minimally invasive delivery of soluble molecules, nanoparticles and microparticles (Jiang et al, 2009).…”

“…What is more, if severe complication occurs, removal of the drug was not so easy for the ophthalmologists. Compared with controlled release formulations (Meng et al, 2014;Huang et al, 2016), CCSDD can reach a higher drug level in designed time and can control the rate of drug release.…”

“…But it is the most invasive, and can lead to numerous significant local complications such as retinal drug toxicity, retinal detachment, vitreous and retinal hemorrhage, floaters, endophthalmitis, lens injury, and elevated intraocular pressure, which will affect the vision of patients (Huang et al, 2016). Consequently, the ideal routes of drug delivery to the posterior segment are from the eye of periocular (Hsu, 2007), which is considered to be minimal painful and direct penetration pathway (Nagai et al, 2014;Huang et al, 2016). It included the retrobulbar, peribulbar, sub-tenon and subconjunctival (SC) routes.…”

Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

“…Furthermore, the ability of up to 1 year's long-term drug delivery shows a clear advantage over the previous reports, such as episcleral films releasing triamcinolone acetonide for 120 days 24,25 and a capsular device releasing dexamethasone for 60 days. 26 Some intravitreal implants have been effective and safe for intraocular use. To date, two ocular drug delivery systems, Vitrasert 27 and Retisert, 28 which are intravitreal sustainedrelease implants of ganciclovir and fluocinolone acetonide, respectively, have been marketed.…”

Insulin-loaded PLGA microspheres for glucose-responsive release

“…In recent decades, a range of long term sustained-release materials have been reported (Hou et al, 2016;Huang et al, 2016;Maulvi et al, 2016). These are commonly based on PLGA, which is a generally recognized as safe (GRAS) excipient certified by the FDA.…”