Potential applications of PLGA film-implants in modulating in vitro drugs release
In this work we evaluate poly(lactic/glycolic) acid (PLGA) film-implants as potential biodegradable devices for controlled release of two different drugs: 5-Fluorouridine (5-FUR), a conventional low molecular weight water-soluble compound and SPf66 malaria vaccine, a therapeutic synthetic polypeptide. Three types of devices were prepared by solvent-casting techniques alone or combined with compression method: simple monolithic discs (SMD), multilayer discs with a central monolithic layer (MLDM), and multilayer discs with a central drug-reservoir (MLDR). For the highly water-soluble drug, 5-FUR, in vitro release from SMD showed an initial burst (24% in 2 h) followed by prolonged release over 20 days. In contrast, from a MLDM (two drug-free PLGA discs were added to the SMD) showed an initial lag-time of 12 days followed by a very fast second release phase. Finally, when the load of this system was increased from 3 to 9%, an extended release over 20 days with a low burst effect was obtained. For SPf66, the central reservoir containing the synthetic polypeptide MLDR reduces the possibility of degradation due to peptide contact with polymer solution. When four layers were added, 10 days sustained-release was obtained without any burst effect. With six layers a moderate pulse was obtained, 18-22 days from the beginning of the release. The results show the suitability of the proposed devices to control release and avoid the burst effect with highly water-soluble drugs; as well as modulate in vitro peptide release.
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