Sustained release study procedure

A rabbit model to assess the possible neuroprotective effects of central acting calcium channel blockers using a nondegradable sustained-release device has been developed (3). In this model an intraocular infusion was used to elevate the intraocular pressure (IOP). To assess the effects of the study drug, IOP was maintained at 40mmHg for over an hour in both treatment and control eyes and was then decreased to a normal level. The procedure was repeated at 48 and 72 hours to simulate IOP spikes in human eyes (3). 

For the drug release profile of homopolymer of DOX, pH 7.4 as well as acidic conditions was decided as the normal pH of blood for sustaining human life is about 7.4, while the endosomes and lysosomes of cells have a more acidic environment [11c]. Therefore, drug release study of homopolymer was carried out in pH 7.4 in phosphate buffer solution and pH 5.5 and 6 in acetate buffer solutions, respectively. A 1 mg of homopolymer was dissolved in 1 ml of distilled water (partially soluble) and loaded in dialysis tube (3,500 Dalton cut-off) and dialyzed against 70 ml of a buffer solution whose pH was maintained at 5.5. An aliquot of the sample was removed and its absorbance at 480 nm was measured as an indication of the release of doxorubicin. Fluorescence also recorded by exciting the solution at 510 nm. Emissions from the free DOX released from homopolymer were observed at 560 nm and 590 nm. The sample was then added back to the solution to maintain the volume of the solution. This procedure was repeated for every 1 h and results were observed for 48 h. It was observed that after 24 h, there was no significance increase in the intensity of fluorescence and UV intensity. The similar procedure was repeated to monitor the drug release at pH 6.0 as well as pH 7.4 and the results are shown in (Fig. 18). The DOX release from homopolymer at pH 7.4 was very minimal. 

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