El-Shabouri M H
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Int J Pharm. 2002 Dec 5;249(1-2):101-8. doi: 10.1016/s0378-5173(02)00461-1.
In this study, cyclosporin-A (Cy-A) a highly lipophilic, poorly absorbable drug can be prepared easily and reproducibly as positively and negatively charged nanoparticles with the aim of improving its bioavailability and reducing its inter- and intra-individual variability. The nanoparticles were prepared by emulsification solvent diffusion method, using lecithin and poloxamer 188 as emulsifiers, and chitosan HCl, gelatin-A or sodium glycocholate (SGC) as charge inducing agents. The prepared nanoparticles were evaluated with respect to particle size, zeta potential, drug content and encapsulation efficiency. The bioavailability Cy-A from nanoparticles in comparison with the currently available Cy-A microemulsion (Neoral) were assessed in beagle dogs. The results obtained revealed that, it was possible to prepare Cy-A as nanoparticles with size range of 104-148 nm. Chitosan HCl and gelatin-A nanoparticles exhibited +31.2 and +23.1 mV zeta potential, respectively; while SGC-nanoparticles exhibited -41.6 mV zeta potential. The in vivo results showed that, chitosan-nanoparticles gave the highest C(max) (2762.8 ng/ml) of Cy-A after 2.17 h (T(max)), while SGC-nanoparticles gave the lowest one (1202.4 ng/ml after 4.0 h). Furthermore, AUC(0-24) of Cy-A from chitosan-nanoparticles was markedly increased by about 2.6-fold when compared with SGC-nanoparticles and increased by about 1.8-fold when compared with the reference Neoral microemulsion. However, in case of gelatin-nanoparticles the AUC(0-24) of Cy-A increased by about 1.8 and 1.2-fold when compared with SGC-nanoparticles and the reference Neoral microemulsion, respectively. The relative bioavailability of Cy-A from chitosan-nanoparticles was increased by about 73%, and by about 18% from gelatin nanoparticles, while it was decreased by about 36% from SGC-nanoparticles.
在本研究中，环孢素A（Cy - A）是一种高度亲脂、吸收性差的药物，为提高其生物利用度并降低个体间和个体内变异性，可轻松且可重复地制备成带正电和负电的纳米颗粒。纳米颗粒通过乳化溶剂扩散法制备，使用卵磷脂和泊洛沙姆188作为乳化剂，壳聚糖盐酸盐、明胶A或甘氨胆酸钠（SGC）作为电荷诱导剂。对制备的纳米颗粒进行了粒径、zeta电位、药物含量和包封率的评估。在比格犬中评估了纳米颗粒中Cy - A与目前可用的Cy - A微乳剂（新山地明）相比的生物利用度。所得结果表明，有可能制备出粒径范围为104 - 148 nm的Cy - A纳米颗粒。壳聚糖盐酸盐纳米颗粒和明胶A纳米颗粒的zeta电位分别为 +31.2和 +23.1 mV；而SGC纳米颗粒的zeta电位为 -41.6 mV。体内结果表明，壳聚糖纳米颗粒在2.17小时（Tmax）后Cy - A的C(max)最高（2762.8 ng/ml），而SGC纳米颗粒的最低（4.0小时后为1202.4 ng/ml）。此外，壳聚糖纳米颗粒中Cy - A的AUC(0 - 24)与SGC纳米颗粒相比显著增加约2.6倍，与参比新山地明微乳剂相比增加约1.8倍。然而，对于明胶纳米颗粒，Cy - A的AUC(0 - 24)与SGC纳米颗粒和参比新山地明微乳剂相比分别增加约1.8倍和1.2倍。壳聚糖纳米颗粒中Cy - A的相对生物利用度提高了约73%，明胶纳米颗粒提高了约18%，而SGC纳米颗粒降低了约36%。
