Albany College of Pharmacy and Health Sciences, Albany, NY 12208, USA.
Colloids Surf B Biointerfaces. 2011 Oct 15;87(2):391-8. doi: 10.1016/j.colsurfb.2011.05.048. Epub 2011 Jun 1.
In this study, fluid precursor formulations for subcutaneous injection and in situ formation of hexagonal phase gels upon water absorption were developed as a strategy to sustain the release of naltrexone, a drug used for treatment of drug addiction. Precursor formulations were obtained by combining BRIJ 97 with propylene glycol (PG, 5-70%, w/w). To study the phase behavior of these formulations, water was added at 10-90% (w/w), and the resulting systems were characterized by polarized light microscopy. Two precursor formulations containing BRIJ:PG at 95:5 (w/w, referred to as BRIJ-95) and at 80:20 (w/w, referred to as BRIJ-80) were chosen. Naltrexone was dissolved at 1% or suspended at 5% (w/w). Precursor formulations were transformed into hexagonal phases when water content exceeded 20%. Water uptake followed second-order kinetics, and after 2-4h all precursor formulations were transformed into hexagonal phases. Drug release was prolonged by the precursor formulations (compared to a drug solution in PBS), and followed pseudo-first order kinetics regardless of naltrexone concentration. The release from BRIJ-80 was significantly higher than that from BRIJ-95 after 48 h. The relative safety of the precursor formulations was assessed in cultured fibroblasts. Even though BRIJ-95 was more cytotoxic than BRIJ-80, both precursor formulations were significantly less cytotoxic than sodium lauryl sulfate (considered moderate-to-severe irritant) at the same concentration (up to 50 μg/mL). These results suggest the potential of BRIJ-based precursor formulations for sustained naltrexone release.
在这项研究中，开发了用于皮下注射的流体前体配方，并在吸收水时原位形成六方相凝胶，作为持续释放纳曲酮（一种用于治疗药物成瘾的药物）的策略。前体配方通过将 BRIJ 97 与丙二醇（PG，5-70%，w/w）结合获得。为了研究这些配方的相行为，以 10-90%（w/w）的比例加水，并通过偏光显微镜对所得系统进行了表征。选择了两种含有 BRIJ:PG 的前体配方，分别为 95:5（w/w，称为 BRIJ-95）和 80:20（w/w，称为 BRIJ-80）。将纳曲酮溶解在 1%或悬浮在 5%（w/w）。当含水量超过 20%时，前体配方转变为六方相。水的吸收遵循二级动力学，2-4 小时后所有前体配方都转变为六方相。与 PBS 中的药物溶液相比，前体配方延长了药物释放，并遵循伪一级动力学，与纳曲酮浓度无关。BRIJ-80 的释放明显高于 BRIJ-95 48 小时后。在前体配方中培养的成纤维细胞中评估了相对安全性。尽管 BRIJ-95 比 BRIJ-80 更具细胞毒性，但两种前体配方在相同浓度（高达 50μg/mL）下的细胞毒性均明显低于十二烷基硫酸钠（被认为是中度至重度刺激性）。这些结果表明基于 BRIJ 的前体配方在持续释放纳曲酮方面具有潜力。
