- Belgrade '18
- Vienna '18
- ESCRS Player
- On Demand
- ESCRS iLearn
- ESCRS YO's
Session Title: Cataract II
Session Date/Time: Saturday 15/02/2014 | 08:30-11:00
Paper Time: 08:58
Venue: Gallus Hall (Level -1)
First Author: : ElisabethBadens FRANCE
Co Author(s): : Yasmine Masmoudi Abir Bouledjouidja Olivier Fornazo Jean-Marie Andre
The present work deals with the development of drug delivery intraocular lenses (IOLs) to prevent postoperative endophthalmitis in cataract surgery. Commercially available rigid and foldable IOLs were impregnated with an anti-inflammatory drug using an innovative and green process. The impregnated IOLs act as Drug Delivery Systems (DDS). Drug impregnation is significant while the transparency and optical properties are preserved. Drug is then released over days following surgery. The innovative aspect of the process is that no toxic organic solvents are used; the impregnated IOLs are then clean.
In order to prevent postoperative infectious complications, a solution can be the use of controlled Drug Delivery Systems (DDS) placed inside the eye. If the DDS is the impregnated IOL, this solution does not require an additional act of the surgeon.
Supercritical fluid technologies have been demonstrated to be a clean and effective alternative to traditional methods of drug and polymer processing. A supercritical fluid is a compound brought at a pressure higher than its critical pressure and a temperature above its critical temperature. It has specific interesting properties such as a liquid-like density and a gas-like viscosity. Supercritical carbon dioxide (P > 7.38 MPa and T > 304.21 K) has been used as an impregnation vehicle of the drug within the polymeric matrix of the IOLs. Commercially available rigid IOLs made from derivative of Poly (Methyl MethAcrylate) (PMMA) as well as foldable IOLs made from Poly 2-hydroxyethyl methacrylate (P-HEMA) have been impregnated with Dexamethasone 21-phosphate disodium, an anti-inflammatory drug, through a discontinuous process. The impregnation efficiency was determined in term of impregnation yield as well as in term of in-vitro drug release kinetics. The influence of some experimental operating conditions was studied by varying the pressure (8 and 20 MPa), the temperature (308 and 333 K), and by adding a co-solvent (ethanol). The influence of the IOLs dioptre was also studied (+8.0 D, +21.0 D, +30.0 D). The transparency and optical properties of IOLs have been characterized after each treatment.
The drug impregnation yields vary from 0.3 to 5.3 wt % (±0.2 %) for the rigid IOLs. Concerning the foldable IOLs, the impregnation yields vary from 2.1 to 7.9 wt % (±0.2 %). Depending on the impregnation process conditions, a foaming phenomenon has been observed. Indeed, in presence of dense carbon dioxide, the polymeric implants plasticize. Thus, during the depressurization step, bubbles of CO2 can be formed within the polymeric matrix. The transparency properties of the resulting IOLs are then degraded. An innovative pre-treatment step has been implemented in order to avoid this foaming phenomenon. It consists in a first step of conditioning the IOLs in presence of pure CO2 either in a static or in a dynamic mode with controlled conditions of pressurization and of depressurization (between 0.01 and 1 MPa/min). Moreover, this innovative pre-treatment step ensures a reproducible state of the implant before carrying out the impregnation, allowing therefore reproducible impregnation results. In vitro drug release studies have been performed in a solution simulating the aqueous humor. The drug release is observed during a period varying from ten to thirty days depending on the impregnation conditions.
An innovative process for the drug impregnation of IOLs has been implemented. The resulting impregnated IOLs do not contain residual organic solvent traces. They can act as Drug Delivery Systems once placed in the eyes at the end of surgery. The impregnation rates obtained are significant and the in vitro drug release studies have shown that the drug is released over a period comprised between ten and thirty days. An innovative pre-treatment step has been implemented in order to avoid the foaming phenomenon. The optical properties and the transparency of the impregnated IOLs are then preserved (see figure 1). Moreover, a reproducible initial state before impregnation is obtained. Figure 1: IOL before (a) and after (b) CO2 treatment. This process applied to IOLs can also be adapted to any polymeric matrix or implant for which a drug impregnation is required. The impregnation can also be carried out using a mixture of drugs. FINANCIAL INTEREST: NONE