Bochot A, Fattal E, Gulik A, Couarraze G, Couvreur P
Laboratoire de Physico-Chimie, Pharmacotechnie, Biopharmacie, URA CNRS 1218, Faculté de Pharmacie, Châtenay-Malabry, France.
Pharm Res. 1998 Sep;15(9):1364-9. doi: 10.1023/a:1011989202488.
The main goal of this study was to develop an ocular controlled release formulation of a model oligonucleotide (pdT16), contained within liposomes dispersed within a thermosensitive gel composed by poloxamer 407.
The influence of the poloxamer concentration 2% or 27% on the stability of the liposomes (PC: CHOL and PC: CHOL: PEG-DSPE) was investigated. The in vitro release profiles of pdT16 from various poloxamer formulations (free pdT16 dispersed within 20% and 27% poloxamer gels, pdT16 encapsulated within liposomes dispersed within 20% and 27% poloxamer gels) were realized using a membrane-free release model.
The dispersion of liposomes within a dilute 2% poloxamer solution resulted in a great leakage of pdT16 from liposomes. However, the destabilization effect of poloxamer was reduced when higher concentration (27%) was used. Poloxamer dissolution was found to control the release process of pdT16, whereas the dispersion of liposomes within 27% poloxamer gel was shown to slow down the diffusion of pdT16 out from the gel.
The dispersion of liposomes within a 27% poloxamer gel presented an interesting system to control the release of a model oligonucleotide compare to a simple gel.
本研究的主要目标是开发一种眼部控释制剂，该制剂包含一种模型寡核苷酸（pdT16），其包裹于分散在由泊洛沙姆407组成的热敏凝胶中的脂质体内。
研究了2%或27%泊洛沙姆浓度对脂质体（PC:CHOL和PC:CHOL:PEG-DSPE）稳定性的影响。使用无膜释放模型实现了pdT16从各种泊洛沙姆制剂（游离pdT16分散在20%和27%泊洛沙姆凝胶中、pdT16包裹于分散在20%和27%泊洛沙姆凝胶中的脂质体内）的体外释放曲线。
脂质体分散在稀释的2%泊洛沙姆溶液中导致pdT16从脂质体大量泄漏。然而，使用较高浓度（27%）时泊洛沙姆的去稳定作用降低。发现泊洛沙姆的溶解控制着pdT16的释放过程，而脂质体分散在27%泊洛沙姆凝胶中可减缓pdT16从凝胶中的扩散。
与简单凝胶相比，脂质体分散在27%泊洛沙姆凝胶中呈现出一种控制模型寡核苷酸释放的有趣体系。
