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S. Eperon, L. Bossy-Nobs, R. Gurny, I. K. Petropoulos, Y. Guex-Crosier; A Drug Delivery System and Intraocular Lens. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5784.
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© ARVO (1962-2015); The Authors (2016-present)
Cataract surgery induces inflammation and may worsen preexisting ocular pathologies. High doses of steroids are often required via oral or injection route, implying risks and side-effects. To avoid them, we developed a biodegradable drug delivery system (DDS) associated to the artificial intraocular lens (IOL).
DDS was prepared using poly(D,L-lactide-co-glycolide) (PLGA) with different Mw. DDS was loaded with triamcinolone acetonide (TA). Cataract surgery was performed on the right eye of pigmented rabbits and IOL associated with DDS was inserted. Four parameters were measured: i) the clinical score (sum of hyperemia, chemosis, corneal edema and discharge, each scored from 0 to 3), ii) the intraocular pressure, iii) the number of inflammatory cells in aqueous humor (AH) and iv) the protein concentration in AH .
The minidisk-like DDS weighed approximately 3 mg and contained around 1 mg of TA. In vitro release studies indicated that the higher the Mw of the DDS, the slower was the release of TA. Rabbits were implanted with IOL wearing i) no DDS (n=4), ii) unloaded DDS (n=4), iii) one loaded DDS (n=7), iv) two loaded DDSs (n=6). IOL insertion with unloaded DDS did not induce more inflammation than IOL without DDS, indicating a good ocular biocompatibility. One loaded DDS (Mw=48’000 Da) could significantly reduce ocular inflammation induced by surgery. Inhibition of protein migration reached 58%, 76% and 61% at 7, 14 and 21 days after surgery, respectively. Two loaded DDS could inhibit inflammation by 94% at 7 days, 97% at 14 days and 90% at 21 days after surgery.
The combination of IOL with DDS made of PLGA and loaded with TA could significantly inhibit post-operative inflammation. This system, loaded with TA or other drugs, may be useful to treat severe pathologies such as exudative age-related macular degeneration (AMD), proliferative vitreoretinopathy and diabetic macular edema.
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