School of Pharmacy and Life Sciences, The Robert Gordon University St Andrew St, Aberdeen, AB25 1HG, UK.
Pharm Res. 2012 Mar;29(3):782-94. doi: 10.1007/s11095-011-0602-7. Epub 2011 Oct 5.
To investigate the use of nano self-assemblies formed by polyallylamine (PAA) modified with 5 or 10% mole fluorenylmethoxy carbonyl (Fmoc(5)/(10)), dimethylamino-1-naphthalenesulfonyl (Dansyl(5)/(10)) and 5% mole cholesteryl group (Ch(5)) for oral hydrophobic drug delivery.
Propofol, griseofulvin and prednisolone were loaded into amphiphilic PAAs. Particle size and morphology of drug-loaded self-assemblies were determined using photon correlation spectroscopy and transmission electron microscopy. Solubilising capacity, in vitro drug release and formulation stability were analysed by HPLC, and in vitro biocompatibility studies (haemolysis and cytotoxicity) were carried out on bovine erythrocytes and Caco-2 cells, respectively. Dansyl(10) and Ch(5) griseofulvin formulations were administered intra-gastrically to rats, and drug plasma levels were analysed by HPLC.
Drug-encapsulated self-assemblies typically have hydrodynamic size of 300-400 nm. Dansyl(10) exhibited universal drug solubiliser property and had significantly improved prednisolone, griseofulvin and propofol solubility by 145, 557 and 224-fold, respectively. Fmoc polymers resulted in modest drug solubility improvement. These polymers were non-haemolytic, did not enhance cytotoxicity compared to unmodified PAA, and demonstrated significant increase in griseofulvin plasma concentration compared to griseofulvin in water after oral administration.
Ch(5) and Dansyl(10) showed promising potential as nano-carriers for oral hydrophobic drug delivery.
研究由聚烯丙胺（PAA）修饰的 5 或 10%摩尔芴甲氧羰基（Fmoc(5)/(10)）、二甲氨基-1-萘磺酰基（Dansyl(5)/(10)）和 5%摩尔胆固醇基团（Ch(5)）形成的纳米自组装物在口服疏水性药物传递中的应用。
将丙泊酚、灰黄霉素和泼尼松龙载入两亲性 PAA 中。采用光子相关光谱法和透射电子显微镜测定载药自组装体的粒径和形态。通过 HPLC 分析增溶能力、体外药物释放和制剂稳定性，分别用牛红细胞和 Caco-2 细胞进行体外生物相容性研究（溶血和细胞毒性）。将 Dansyl(10)和 Ch(5)灰黄霉素制剂经胃内给药给大鼠，并通过 HPLC 分析药物血浆水平。
载药自组装体的水动力粒径通常为 300-400nm。Dansyl(10)具有普遍的药物增溶剂性质，使泼尼松龙、灰黄霉素和丙泊酚的溶解度分别提高了 145、557 和 224 倍。Fmoc 聚合物使药物溶解度略有提高。这些聚合物无溶血作用，与未修饰的 PAA 相比，不会增强细胞毒性，并且在口服给药后与灰黄霉素在水中相比，灰黄霉素的血浆浓度显著增加。
Ch(5)和 Dansyl(10)显示出作为口服疏水性药物传递的纳米载体的有前途的潜力。
