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S. H. Boddu, J. Jwala, R. Vaishya, D. Pal, A. K. Mitra; In situ Polymeric Biodegradable Gelling Systems of Steroids for the Treatment of Retinal Diseases. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5966.
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Repeated intravitreal injections of steroids in the treatment of retinal diseases pose potential problems like retinal detachment, hemorrhage, endophthalmitis, lack of patient compliance and risk of drug precipitation due to poor solubility. The aim of this study is to develop a novel biodegradable injectable in situ gelling system which can be subconjunctivally administered for the treatment of retinal diseases.
Steroidal nanoparticles of dexamethasone (DEX), hydrocortisone acetate (HA) and prednisolone acetate (PA) were prepared with PLGA 50:50 and PLGA 65:35 by dialysis method and O/W emulsion/solvent evaporation methods. Nanoparticles were studied for size, entrapment efficiency,crystallinity, surface morphology, release properties and time dependent cytotoxicity. .
O/W emulsion/solvent evaporation method resulted in higher entrapment efficiencies compared to dialysis method. Hence, nanoparticles prepared by emulsion technique were used for further studies. Entrapment efficiencies were found to be 78.2%, 93.1% and 93.6% for DEX, HA and PA respectively. Sustained release of steroids was observed from the nanoparticles prepared by O/W emulsion/solvent evaporation method and release rate constants for DEX, HA and PA were found to be 6.73, 2.24, 3.40 h-1/2 respectively. The release rate constants of DEX, HA and PA from PLGA 65:35 nanoparticles were found to be 5.11, 1.31 and 3.16 h-1/2 respectively. Such nanoparticles were suspended in biodegradable thermosensitive polymeric (PLGA-PEG-PLGA) gels for subconjunctival administration. PLGA-PEG-PLGA was synthesized and characterized for its swelling properties, thermogelling behavior and rheology. Stability studies of steroidal nanoparticles along with PLGA-PEG-PLGA were carried out in glass vials at 25°C ± 2°C, 30°C ± 2°C and 40°C ± 2°C as per the ICH guidelines. Final formulations were prepared by suspending required quantity of nanoparticles in 23% W/W aqueous solution of PLGA-PEG-PLGA polymer. This mixture was freeze dried and sterilized in vials for future reconstitution.
Novel gelling nanoparticle based drug delivery system may provide sustained delivery of steroids following a single episcleral administration.
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